Search tips
Search criteria 


Logo of springeropenLink to Publisher's site
Naunyn-Schmiedeberg's Archives of Pharmacology
Naunyn Schmiedebergs Arch Pharmacol. 2016; 389: 671–694.
Published online 2016 April 30. doi:  10.1007/s00210-016-1247-1
PMCID: PMC4903110

Pharmacological treatment options for mast cell activation disease


Mast cell activation disease (MCAD) is a term referring to a heterogeneous group of disorders characterized by aberrant release of variable subsets of mast cell (MC) mediators together with accumulation of either morphologically altered and immunohistochemically identifiable mutated MCs due to MC proliferation (systemic mastocytosis [SM] and MC leukemia [MCL]) or morphologically ordinary MCs due to decreased apoptosis (MC activation syndrome [MCAS] and well-differentiated SM). Clinical signs and symptoms in MCAD vary depending on disease subtype and result from excessive mediator release by MCs and, in aggressive forms, from organ failure related to MC infiltration. In most cases, treatment of MCAD is directed primarily at controlling the symptoms associated with MC mediator release. In advanced forms, such as aggressive SM and MCL, agents targeting MC proliferation such as kinase inhibitors may be provided. Targeted therapies aimed at blocking mutant protein variants and/or downstream signaling pathways are currently being developed. Other targets, such as specific surface antigens expressed on neoplastic MCs, might be considered for the development of future therapies. Since clinicians are often underprepared to evaluate, diagnose, and effectively treat this clinically heterogeneous disease, we seek to familiarize clinicians with MCAD and review current and future treatment approaches.

Keywords: Mast cell, Mast cell activation disease, Systemic mastocytosis, Systemic mast cell activation syndrome, Therapy


Mast cells (MCs, Fig. Fig.1)1) are immune cells of hematopoietic origin found in all human tissues, especially at the environmental interfaces. They act as both effector and regulatory cells and play a central role in adaptive and innate immunity (Anand et al. 2012; Gri et al. 2012). Their important role in immunological as well as non-immunological processes is reflected by the large number of mediators (>200) including pre-stored ones such as histamine and tryptase as well as numerous mediators synthesized de novo in response to allergic or non-immune triggers such as chemokines and cytokines, by which MCs may influence other cells (Lundequist and Pejler 2011; Ibelgaufts 2016). Their evolved arrays of sensory and response mechanisms engender diverse havoc when MC dysfunction emerges.

Fig. 1
May-Grünwald/Giemsa stain of a resting human mast cell and a mast cell following activation-induced degranulation. Note the loss of granule staining. Mast cells obtained from the human bone marrow, magnification 1000×

The umbrella term mast cell activation disease (MCAD; Akin et al. 2010) comprises the full spectrum of primary systemic MC disease, i.e., systemic mastocytosis (SM) which is further divided into several subtypes (Valent et al. 2007; Tables Tables11 and and2),2), primary MC activation syndrome (MCAS; Table Table3;3; Molderings et al. 2011a; Hamilton et al. 2011; Valent et al. 2012), and MC leukemia (MCL). Pathogenetically, MCAD denotes a group of polygenic MC disorders (Molderings 2015, 2016) characterized by aberrant release of variable subsets of MC mediators and also an accumulation of either morphologically altered and immunohistochemically identifiable mutated MCs due to MC proliferation (SM and MCL) or morphologically ordinary MCs due to decreased apoptosis (MCAS; Kohno et al. 2005; Aichberger et al. 2009; Karlberg et al. 2010a). According to recent molecular genetic findings (Molderings 2015, 2016; Haenisch et al. 2014; Lasho et al. 2016), the subclasses and clinical subtypes of MCAD do not represent distinct disease entities but should be more accurately regarded as variable presentations of a common generic state of MC dysfunction (Molderings et al. 2007, 2010; Hermine et al. 2008; Akin et al. 2010). Due to both the widespread distribution of MCs and the great heterogeneity of aberrant mediator expression patterns, symptoms can occur in virtually all organs and tissues; hence, the clinical presentation of MCAD is very diverse, sometimes to the even-further-confounding point of presenting opposite abnormalities in different patients (or even in the same patient at different times, or in different sites in the same patient at the same time). While the prevalence of SM in Europeans ranges between 0.3 and 13 per 100,000 (Haenisch et al. 2012; Cohen et al. 2014; van Doormaal et al. 2013), the prevalence of MCAS may be as high as 17 % (in Germany; Molderings et al. 2013a, b).

Table 1
WHO 2008 diagnostic criteria for systemic mastocytosis (Valent et al. 2001)
Table 2
Classification of systemic mastocytosis (modified form Valent et al. 2007)
Table 3
Current provisional criteria to define mast cell activation syndrome (MCAS; modified from Afrin and Molderings 2014)

This review focuses on the current state of drug therapy in SM and MCAS and describes perspectives of promising new approaches for drug treatment. Compounds in various stages of preclinical and clinical development are summarized in tables. We first describe drugs that are currently available and either are used on a regular basis in MCAD therapy or have been used successfully in single MCAD cases. In this context, it should be noted that there is no official guideline for treatment of MCAD.

Treatment options

Due to its genetic roots, MCAD generally is regarded as incurable. Recent mutational studies revealed that each patient has an individual pattern of genetic and epigenetic alterations which may affect the intracellular signal transduction pathways and receptive sites involved in sensory perception. As a consequence, mediator formation and release as well as inhibition of apoptosis and/or increase in proliferation are determined by individual genetic and epigenetic conditions (Fig. (Fig.2)2) and represent potential targets for therapy. Hence, there is need of highly personalized therapy for the disease. Unfortunately (with regard to easy detection), most genetic alterations (with a few exceptions such as certain mutations in tyrosine kinase KIT, e.g., KITD816V) do not alter the morphology and immunohistochemistry of the surface of the affected MCs. Thus, in most cases except for patients with the reliably identifiable D816V mutation, it cannot be decided by simple tests whether MCs found in biopsies are genetically altered MCs or physiological MCs.

Fig. 2
Scheme of conditions responsible in MCAD for the development of individual phenotypes

First-line treatment options

Step 1 in managing most situations of inappropriate MC activation is identifying the individual patient’s unique triggers (chemical, physical, or otherwise) as precisely as possible and then desensitizing when possible (in truth, rarely) and otherwise practicing avoidance. With respect to drug treatment, only a few clinical therapeutic trials have been conducted in SM (midostaurin, cladribine, masitinib; Table Table4),4), and there have been no therapeutic trials in MCAS yet. Most information about therapeutic effectiveness in MCAD has been found in small case series (Table (Table4)4) and single case reports, perhaps unsurprising given the mutational heterogeneity of the disease and thus the heterogeneity of its patterns of clinical presentation and therapeutic responsiveness. Therefore, in the future, it may be helpful to establish an international patient registry in partnership with existing registries so that issues related to molecular and clinical MCAD phenotypes can be adequately addressed. As the primary feature of MCAD is inappropriate MC activation (Molderings et al. 2011a, b; Pardanani 2013; Cardet et al. 2013), mainstays of first-line management are identification and avoidance of triggers plus therapies to control MC mediator production (both primary as well as secondary/reactive; Table Table5)5) as well as their action (Table (Table66).

Table 4
Case series and clinical therapeutic trials in systemic mastocytosis and mast cell activation syndrome
Table 5
First-line drugs which can potentially be used in the treatment of mast cell (MC) activation disease and their target location and mechanisms of action
Table 6
Symptomatic treatment (orally as needed) in MCAD (modified from Molderings et al. 2014)

Subordinate therapeutic options

Continuous diphenhydramine infusion

Occasional patients suffer nearly continuous anaphylactoid and/or dysautonomic states poorly controlled by intermittently dosed epinephrine, antihistamines, and steroids. As discussed in more detail below, some such patients are particularly triggered by a wide range of medication excipients, making it challenging for them to tolerate trials of any adulterated (non-pure) medications, and yet some modicum of stability is required to pursue medication trials in such patients. Diphenhydramine is a well-tolerated histamine H1 receptor blocker (that among other non-threatening adverse affects can cause dizziness and an increase in appetite) which can quickly suppress MC activation and is used to treat allergic reactions and anaphylaxis. However, its half-life is as short as 1 h ( Intermittently dosed, though, its initial therapeutic serum level rapidly declines to subtherapeutic levels and the patient seesaws into yet another flare. The safety of continuous diphenhydramine infusion was established in trials of the “BAD” regimen (diphenhydramine [Benadryl], lorazepam [Ativan], and dexamethasone) in refractory chemotherapy-induced emesis in adult and pediatric patients (Dix et al. 1999; Jones et al. 2007). In a small series of ten MCAS patients suffering almost continuous anaphylactoid/dysautonomic flares, continuous diphenhydramine infusion at 10–14.5 mg/h appeared effective in most patients at dramatically reducing flare rates and appeared safely sustainable at stable dosing for at least 21 months (Afrin 2015). Stabilization has enabled successful trials of other helpful medications, but no patient has yet successfully stopped continuous diphenhydramine infusion.

Acute and chronic immunosuppressive therapies

Though typically not first-line, acute and chronic immunosuppressive therapies can be considered (Fig. (Fig.3;3; Table Table7)7) and may be particularly appropriate for patients possibly manifesting an autoimmune component of the disease as might be suggested by the presence, for example, of anti-IgE or anti-IgE-receptor antibodies. Glucocorticoids may exert beneficial effects in MCAD, including a decrease in production of stem cell factor (SCF, and possibly other cytokines) and a decrease in MC activation, by various mechanisms which have been extensively reviewed by Oppong et al. 2013. Glucocorticoids at doses >20 mg prednisone equivalent per day are frequently needed to effectively control otherwise refractory acute (and chronic) symptoms. Their chronic toxicity profile is disadvantageous for long-term use, but such toxicities have to be accepted in some cases. The influence of azathioprine, methotrexate, ciclosporine, hydroxyurea, and tamoxifen on MC activity can vary from no to moderate effect depending on individual disease factors. As in therapy of rheumatoid arthritis, azathioprine and methotrexate can be used in daily doses lower than those used in cancer or immunosuppressive post-transplant therapy. Effective MCAD therapy with ciclosporine requires doses as high as those used in transplantation medicine (M. Raithel, personal communication). Methotrexate has to be administered parenterally to be effective (unpublished observation, G.J. Molderings), and in the risk-benefit analysis, a possible non-immunologic histamine release from MCs (Estévez et al. 1996) has to be considered. Hence, use of the compound should be limited to MCAD with methotrexate-sensitive comorbidities (e.g., rheumatoid arthritis and vasculitis).

Fig. 3
Suggested treatment options for mast cell activation disease. All drugs should be tested for tolerance in a low single dose before therapeutic use, if their tolerance in the patient is not known from an earlier application. For further details of indication, ...
Table 7
Second- and third-line drugs which can potentially be used in the treatment of mast cell activation disease and their target location and mechanisms of action

Recently, the humanized anti-IgE murine monoclonal antibody omalizumab has been described in multiple case reports as safe and effective in MCAD (e.g., Molderings et al. 2011b; Kontou-Fili et al. 2010; Bell and Jackson 2012; Kibsgaard et al. 2014), though a definitive trial has yet to be conducted. Since treatment with omalizumab has an acceptable risk-benefit profile, it should be considered in cases of MCAD resistant to at least a few lines of therapy. The drug’s expense likely consigns it to third-line (or later) treatment (Table (Table7).7). If elevated prostaglandin levels induce symptoms such as persistent flushing, inhibition of cyclooxygenases by incremental doses of acetylsalicylic acid (ASA; 50–350 mg/day) may be used with extreme caution, since ASA can induce MC degranulation probably due its chemical property as an organic acid. The leukotriene antagonist montelukast (possibly more effective at twice-daily dosing; personal observation, L.B. Afrin) and the 5-lipoxygenase inhibitor zileuton may be useful adjuvants in people with MCAD, particularly in those with refractory gastrointestinal and urinary symptoms (Tolar et al. 2004; Turner et al. 2012; Akhavein et al. 2012).

Studies of kinase inhibitors, both on-market (e.g., imatinib, nilotinib, dasatinib) and experimental (e.g., midostaurin, masitinib), have yielded variable responses in SM ranging from no response to partial or even complete responses (Fig. (Fig.3;3; Table Table8).8). As with all drugs used in therapy of MCAD, their therapeutic success seems to be strongly dependent on the individual patient, again underscoring the observed mutational heterogeneity of the disease. In formal studies in SM patients, although some kinase inhibitors reduced MC burden as reflected by histological normalization in bone marrow and improved laboratory surrogate markers (e.g., tryptase level in blood), at best only partial improvement of mediator-related symptoms was achieved (Droogendijk et al. 2006; Gotlib et al. 2008; Verstovsek et al. 2008; Vega-Ruiz et al. 2009). There has been repeated suggestion that symptoms in MCAD may be due more to mediator release from normal MCs secondarily activated by pathologically overactive, mutated MCs (Galli and Costa 1995; Rosen and Goetzl 2005; Boyce 2007; Kaneko et al. 2009; Fig. Fig.22 in Molderings et al. 2014), helping to explain why intensity and pattern of symptoms do not correlate with degree of MC proliferation and infiltration (Topar et al. 1998; Hermine et al. 2008; Broesby-Olsen et al. 2013; Erben et al. 2014; Quintás-Cardama et al. 2013). Distinction in pathways in the MC which promote MC proliferation vs. mediator production/release may explain why kinase inhibitors reduce MC burdens and MC-driven symptoms to different degrees (Droogendijk et al. 2006; Gotlib et al. 2008; Verstovsek et al. 2008; Vega-Ruiz et al. 2009; Table Table8).8). However, in some case reports, kinase inhibitors have been significantly effective at relieving symptoms. Thus, in spite of potential serious adverse effects of these drugs, a therapeutic trial may be justified in individual cases at an early stage. Partial and complete responses have been reported with some of these agents in MCAS too (e.g., Afrin 2010, 2011, 2012, 2015; Afrin et al. 2015a). Dosing of the kinase inhibitors in the individual often is considerably lower than how such drugs are dosed for other applications (e.g., imatinib, sunitinib; Afrin et al. 2015a). Possibly due to the causative mutations in multiple genes leading to simultaneous activation of multiple intracellular pathways, multitargeted kinase inhibitors such as midostaurin and sunitinib may be more effective than drugs which selectively downregulate only one intracellular pathway.

Table 8
Kinase inhibitors which can potentially be used as fourth-line drugs in the treatment of mast cell activation disease and their target location and mechanisms of action

In the mastocytosis patient with significant MC burden and/or an aggressive clinical course, cytoreductive drugs are prescribed (Lim et al. 2009; Valent et al. 2010). Unfortunately, effective cytoreductive therapies in SM presently are few in number and typically offer only modest response rates, qualities, and durations. Cytoreductive options include interferon-α and 2-chlorodeoxyadenosine (cladribine, 2-CdA; Fig. Fig.33 and Table Table9).9). Interferon-α is frequently combined with prednisone and is commonly used as cytoreductive therapy for aggressive SM. It ameliorates mastocytosis-related organopathy in a proportion of cases but can be associated with considerable adverse effects (e.g., flu-like symptoms, myelosuppression, depression, hypothyroidism), which may limit its use in MCAD (Simon et al. 2004; Butterfield 2005). PEGylated interferon-α has been shown to be as efficacious as and less toxic than the non-PEGylated form in some myeloproliferative neoplasms, but it has not been specifically studied in MCAD. 2-Chlorodeoxyadenosine is generally reserved for last-choice treatment of patients with aggressive SM who are either refractory or intolerant to interferon-α. Potential toxicities of 2-CdA include significant and potentially prolonged myelosuppression and lymphopenia with increased risk for opportunistic infections.

Table 9
Last-choice drugs which can potentially be used in the treatment of mast cell activation disease and their target location and mechanisms of action. R-review article (further references therein)

Last resorts

Polychemotherapy, including intensive induction regimens of the kind used in treating acute myeloid leukemia, as well as high-dose therapy with stem cell rescue, are approaches restricted to rare, selected patients. Allogeneic stem cell transplantation sometimes yields remissions in mastocytosis long thought impermanent (Spyridonidis et al. 2004; Nakamura et al. 2006; Bae et al. 2013; Gromke et al. 2013), though recent data may offer new hope (Ustun et al. 2014).

Investigational drugs

There are several drugs approved for indications other than MCAD which already have been successfully used in isolated cases with MCAD (Table (Table10).10). In cases of unsuccessful first- to fourth-line therapy, these compounds may be considered as treatment options.

Table 10
Drugs successfully (or not) used off-label to treat isolated cases of mast cell activation disease

A variety of drugs have been shown to inhibit MC growth, to decrease MC mediator release, and/or to relieve mediator-induced symptoms in in vitro and in vivo animal models (Table (Table11).11). Some of these drugs are approved for certain indications (such as ambroxol, statins, mefloquine, and ruxolitinib) and, thus, may be used (if accessible given financial considerations for some agents) if MCAD patients suffer from both the disorder of indication (e.g., hypercholesterolemia—statins, mucous congestion—ambroxol, polycythemia vera—ruxolitinib) and MCAD. An important question is what the role of the other compounds without approved indications should be in clinical practice. There are several challenges that may hamper the clinical introduction of novel targeted therapies in general. Some of these challenges include inherent problems in the translation of preclinical findings to the clinic, the presence of multiple coactive deregulated pathways in the disease, and questions related to the optimal design of clinical trials (e.g., eligibility criteria and endpoints). In particular, the testing of novel targeted treatment in an isolated fashion may be problematic and may in fact underestimate the effectiveness of these novel compounds. It is reasonable to assume that combination therapy will be the key to target parallel critical pathways.

Table 11
Investigational drugs which might have activity against mast cell activation disease since they induce apoptosis of mast cells and/or suppress mast cell mediator release in vitro and/or in vivo

General considerations on drug treatment of MCAD

Although no biomarkers of symptomaticity or therapeutic response are yet validated, the tolerability and efficacy of most therapies tried in MCAD (starting, and escalating in dosage and composition, cautiously) become clinically evident within 1–2 months. Modest experiments with alternative dosages and/or dosing frequencies are not unreasonable. Therapies clearly shown clinically helpful should be continued; therapies not meeting this high bar should be halted to avoid the troublesome polypharmacy that can easily develop in such patients. With no predictors of response yet available, a cost-based approach to sequencing therapeutic trials in a given patient seems reasonable. It is not even clear yet that medications targeted at mediators found elevated in diagnostic testing (e.g., antihistamines in patients with elevated histamine, non-steroidal anti-inflammatory drugs in patients with elevated prostaglandins, leukotriene inhibitors in patients with elevated leukotrienes) are reliably effective, again perhaps unsurprising given the multitude of MC mediators and the complexity of the signaling networks dysregulated by the multiple mutations in MC regulatory elements present in most MCAD patients. Successful regimens appear highly personalized.

Multiple simultaneous (or nearly so) changes in the medication regimen are discouraged since such can confound identification of the specific therapy responsible for a given improvement (or deterioration). Ineffective or harmful agents should be stopped promptly. Prescribers should be aware that although rapid demonstration of intolerance of a new medication (or a new formulation of a previously well-tolerated medication) often suggests excipient reactivity as further discussed below, some active drug molecules themselves (e.g., cromolyn) sometimes cause an initial symptom flare which usually soon abates. Temporary waiver of gluten-, yeast-, and cow milk protein-containing foods during the initial 3–4 weeks of drug therapy can improve the response rate (Biesiekierski et al. 2011; Rodrigo et al. 2013; own unpublished experiences). When MCAD is suspected, therapies that strongly activate the immune system (e.g., vaccinations with live vaccines or autohemotherapy) must be given with caution (especially if similar therapies were previously already poorly tolerated), as such interventions sometimes dramatically worsen MCAD acutely and/or chronically.

Any drug can induce intolerance symptoms in the individual MCAD patient. In some MCAD patients, the disease creates such remarkable states of not only constitutive MC activation but also aberrant MC reactivity that such patients unfortunately experience a great propensity to react adversely to a wide variety of medication triggers. Those MCAD patients begin demonstrating (either acutely or subacutely) odd/unusual/weird/strange/bizarre/unexpected symptoms soon after beginning new medications. It is very important to note that such patients often demonstrate even a greater propensity to react to medication excipients (i.e., fillers, binders, dyes, preservatives) than to the active ingredients. When the patient tries one or more alternative formulations of a medication with the same active ingredient but sharing as few as possible (preferably none) of the excipients in the offending formulation, the patient may discover the medication to be at least tolerable and perhaps even quite effective. Furthermore, such a scenario obviously provides the patient (and physician and pharmacist) a great opportunity to identify one or more of the specific excipients which are triggering abnormal reactivity in the patient’s dysfunctional MCs, and it is those specific excipients—not the medication as a whole—that should be added to the patient’s allergy list and screened against all present medications being taken by the patient and against all future medications proposed for the patient. An MCAD patient’s physician would be wise to not assume, just because an excipient is very widely used in many medication products and appears innocuous and well tolerated in the vast majority of patients, that the same excipient will necessarily be tolerated well in MCAD patients (unpublished observation of the authors). Sometimes the specificity of the reaction is quite extraordinary. For example, patients who react to wood-based microcrystalline cellulose might tolerate cotton-based microcrystalline cellulose without any difficulty at all, or vice versa. In some cases, the pharmacist is unable to identify alternative commercially available formulations sharing few to none of the excipients in the offending formulation, and in those cases, a compounding pharmacist may need to be engaged to identify/develop a custom-compounded formulation the patient can tolerate. (There can be geographic and financial challenges in accessing compounding pharmacies, though.) Occasionally, MCAD patients may be so remarkably reactive to such a wide range of excipients that they can only tolerate a given medication when provided as pure drug salt, reconstituted in water (without preservatives). Intolerance symptoms can be mediated by IgE antibodies, though this scenario appears to be rare since the symptoms are usually not ameliorated by the anti-IgE monoclonal antibody omalizumab (unpublished observation, G.J. Molderings). Alternatively, they may be mediated by IgG antibodies, raising the question of whether gamma globulin (if itself tolerable) might be a helpful adjunct therapy in such patients (perhaps by directly targeting the MC surface’s IgG receptors or via indirect pathways). Recently, a MC-specific receptor termed MRGPRX2 has been identified which appears to be crucially involved in pseudo-allergic drug reactions (McNeil et al. 2015; Seifert 2015).

Drugs which should not be used in MCAD

Several drugs have the ability to trigger MC mediator release. A compilation of drugs known to be associated with a high risk of release of mediators from MCs is given in Table Table12.12. However, there often are therapeutic alternatives to these drugs (Table (Table1212).

Table 12
Compilation of drugs associated with a high risk of release of mediators from mast cells and their therapeutic alternatives (compiled from Mousli et al. 1994; Sido et al. 2014; Afrin et al. 2015b; McNeil et al. 2015)

Conclusions and future perspectives

The therapeutic management of individuals with MCAD is complex and requires reviewing the entire spectrum of symptoms. The paucity of randomized, controlled studies makes treatment of refractory disease challenging and requires patience, persistence, and a methodical approach on the parts of both patient and managing provider(s). Delayed control of the symptoms may increase morbidity. Effective therapy often consists simply of antihistamines and MC-stabilizing compounds supplemented with medications targeted at specific symptoms and complications (Table (Table13).13). Current treatment options for refractory disease are based mainly on observational studies and case reports. Until larger randomized, controlled trials become available to give more guidance on therapy for refractory disease, clinicians should use the available data in conjunction with their clinical expertise and the adverse effect profile of the available drugs to make treatment decisions. More research is certainly needed to better understand MCAD pathobiology, in particular to determine which deregulated genes contribute to a specific symptom or symptom cluster. The greatest challenge in translational research for the discovery of new rational therapies requires a highly interactive interdisciplinary approach engaging basic science labs and clinicians. Understanding of the key components might hasten the progress of novel treatment for all these devastating MCAD phenotypes.

Table 13
Schematic summary of selected potential targets of pharmacological interventions in MCAD


The publication of this article was financially supported by the Förderclub Mastzellforschung e.V.


  • Abdulkadir H, Grootens J, Kjellander M, Hellstram Lindberg E, Nilsson G, Ungerstedt J (2015) Histone deacetylase inhibitor SAHA mediates epigenetic silencing of KIT D816V mutated systemic mastocytosis primary mast cells and selective apoptosis of mutated mast cells. Blood;126: abstract 2834
  • Adachi S, Maruyama T, Kondo T, Todoroki T, Fukao K. The prevention of postoperative intraperitoneal adhesions by tranilast: N-(3′,4′-dimethoxycinnamoyl)anthranilic acid. Surg Today. 1999;29:51–54. doi: 10.1007/BF02482970. [PubMed] [Cross Ref]
  • Afrin LB. Mast cell activation disorder masquerading as pure red cell aplasia. Int J Hematol. 2010;91:907–908. doi: 10.1007/s12185-010-0605-x. [PubMed] [Cross Ref]
  • Afrin LB. Polycythemia from mast cell activation syndrome: lessons learned. Am J Med Sci. 2011;342:44–49. doi: 10.1097/MAJ.0b013e31821d41dd. [PubMed] [Cross Ref]
  • Afrin LB. Mast cell activation syndrome masquerading as agranulocytosis. Mil Med. 2012;177:113–117. doi: 10.7205/MILMED-D-11-00111. [PubMed] [Cross Ref]
  • Afrin LB. Utility of hydroxyurea in mast cell activation syndrome. Exp Hematol Oncol. 2013;2:28. doi: 10.1186/2162-3619-2-28. [PMC free article] [PubMed] [Cross Ref]
  • Afrin LB. Utility of continuous diphenhydramine infusion in severe mast cell activation syndrome. Blood. 2015;126:5194.
  • Afrin LB, Molderings GJ. A concise, practical guide to diagnostic assessment for mast cell activation disease. World J Hematol. 2014;3:1–17. doi: 10.5315/wjh.v3.i1. [Cross Ref]
  • Afrin LB, Cichocki FM, Patel K, Molderings GJ. Successful treatment of mast cell activation syndrome with sunitinib. Eur J Haematol. 2015;95:595–597. doi: 10.1111/ejh.12606. [PubMed] [Cross Ref]
  • Afrin LB, Pöhlau D, Raithel M, Haenisch B, Dumoulin FL, Homann J, Mauer UM, Harzer S, Molderings GJ. Mast cell activation disease: an underappreciated cause of neurologic and psychiatric symptoms and diseases. Brain Behav Immun. 2015;50:314–321. doi: 10.1016/j.bbi.2015.07.002. [PubMed] [Cross Ref]
  • Aichberger KJ, Gleixner KV, Mirkina I, Cerny-Reiterer S, Peter B, Ferenc V, Kneidinger M, Baumgartner C, Mayerhofer M, Gruze A, Pickl WF, Sillaber C, Valent P. Identification of proapoptotic Bim as a tumor suppressor in neoplastic mast cells: role of KIT D816V and effects of various targeted drugs. Blood. 2009;114:5342–5351. doi: 10.1182/blood-2008-08-175190. [PubMed] [Cross Ref]
  • Akhavein A, Patel NR, Minoyappa PK, Glover SC. Allergic mastocytic gastroenteritis and colitis: an unexplained etiology in chronic abdominal pain and gastrointestinal dysmotility. Gastroenterol Res Pract. 2012;2012:950582. doi: 10.1155/2012/950582. [PMC free article] [PubMed] [Cross Ref]
  • Akin C, Valent P, Metcalfe D. Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol. 2010;126:1099–1104. doi: 10.1016/j.jaci.2010.08.035. [PMC free article] [PubMed] [Cross Ref]
  • Aldi S, Takano KI, Tomita K, Koda K, Chan NY, Marino A, Salazar-Rodriguez M, Thurmond RL, Levi R. Histamine H4-receptors inhibit mast cell renin release in ischemia/reperfusion via PKCε-dependent aldehyde dehydrogenase type-2 activation. J Pharmacol Exp Ther. 2014;349:508–517. doi: 10.1124/jpet.114.214122. [PubMed] [Cross Ref]
  • Alexandrakis MG, Kyriakou DS, Kempuraj D, Huang M, Boucher W, Seretakis D, Theoharides TC. The isoflavone genistein inhibits proliferation and increases histamine content in human leukemic mast cells. Allergy Asthma Proc. 2003;24:373–377. [PubMed]
  • Aman J, van Bezu J, Damanafshan A, Huveneers S, Eringa EC, Vogel SM, Groeneveld AB, Vonk Noordegraaf A, van Hinsbergh VW, van Nieuw Amerongen GP. Effective treatment of edema and endothelial barrier dysfunction with imatinib. Circulation. 2012;126:2728–2738. doi: 10.1161/CIRCULATIONAHA.112.134304. [PubMed] [Cross Ref]
  • Anand P, Singh B, Jaggi AS, Singh N. Mast cells: an expanding pathophysiological role from allergy to other disorders. Naunyn Schmiedeberg’s Arch Pharmacol. 2012;385:657–670. doi: 10.1007/s00210-012-0757-8. [PubMed] [Cross Ref]
  • Baba A, Tachi M, Ejima Y, Endo Y, Toyama H, Matsubara M, Saito K, Yamauchi M, Miura C, Kazama I. Anti-allergic drugs tranilast and ketotifen dose-dependently exert mast cell-stabilizing properties. Cell Physiol Biochem. 2016;38:15–27. doi: 10.1159/000438605. [PubMed] [Cross Ref]
  • Babaei S, Bayat M. Effect of pentoxifylline administration on mast cell numbers and degranulation in a diabetic and normoglycemic rat model wound healing. Iran Red Crescent Med J. 2012;14:483–487. [PMC free article] [PubMed]
  • Bachelet I, Munitz A, Moretta A, Moretta L, Levi-Schaffer F. The inhibitory receptor IRp60 (CD300a) is expressed and functional on human mast cells. J Immunol. 2005;175:7989–7995. doi: 10.4049/jimmunol.175.12.7989. [PubMed] [Cross Ref]
  • Bae MH, Kim HK, Park CJ, Seo EJ, Park SH, Cho YU, Jang S, Chi HS, Lee KH. A case of systemic mastocytosis associated with acute myeloid leukemia terminating as aleukemic mast cell leukemia after allogeneic hematopoietic stem cell transplantation. Ann Lab Med. 2013;33:125–129. doi: 10.3343/alm.2013.33.2.125. [PMC free article] [PubMed] [Cross Ref]
  • Baek OS, Kang OH, Choi YA, Choi SC, Kim TH, Nah YH, Kwon DY, Kim YK, Kim YH, Bae KH, Lim JP, Lee YM. Curcumin inhibits protease-activated receptor-2 and -4-mediated mast cell activation. Clin Chim Acta. 2003;338:135–141. doi: 10.1016/j.cccn.2003.08.015. [PubMed] [Cross Ref]
  • Bairlein M (2010) Characterization of the small molecule kinase inhibitor SU11248 (sunitinib/SUTENT) in vitro and in vivo—towards response prediction in cancer therapy with kinase inhibitors. TU Munich, Munich, Germany, Medical thesis
  • Barete S, Lortholary O, Damaj G, Hirsch I, Chandesris MO, Elie C, Hamidou M, Durieu I, Suarez F, Grosbois B, Limal N, Gyan E, Larroche C, Guillet G, Kahn JE, Casassus P, Amazzough K, Coignard-Biehler H, Georgin-Lavialle S, Lhermitte L, Fraitag S, Canioni D, Dubreuil P, Hermine O. Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis. Blood. 2015;126:1009–1016. doi: 10.1182/blood-2014-12-614743. [PubMed] [Cross Ref]
  • Bell MC, Jackson DJ. Prevention of anaphylaxis related to mast cell activation syndrome with omalizumab. Ann Allergy Asthma Immunol. 2012;108:383–384. doi: 10.1016/j.anai.2012.02.021. [PMC free article] [PubMed] [Cross Ref]
  • Bibi S, Arslanhan MD, Langenfeld F, Jeanningros S, Cerny-Reiterer S, Hadzijusufovic E, Tchertanov L, Moriggl R, Valent P, Arock M. Co-operating STAT5 and AKT signaling pathways in chronic myeloid leukemia and mastocytosis: possible new targets of therapy. Haematologica. 2014;99:417–429. doi: 10.3324/haematol.2013.098442. [PubMed] [Cross Ref]
  • Bidri M, Royer B, Averlant G, Bismuth G, Guillosson JJ, Arock M. Inhibition of mouse mast cell proliferation and proinflammatory mediator release by benzodiazepines. Immunopharmacology. 1999;43:75–86. doi: 10.1016/S0162-3109(99)00046-6. [PubMed] [Cross Ref]
  • Biesiekierski JR, Newnham ED, Irving PM, Barrett JS, Haines M, Doecke JD, Shepherd SJ, Muir JG, Gibson PR. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol. 2011;106:508–514. doi: 10.1038/ajg.2010.487. [PubMed] [Cross Ref]
  • Böhm A, Sonneck K, Gleixner KV, Schuch K, Pickl WF, Blatt K, Peter B, Herrmann H, Schernthaner GH, Pehamberger H, Rabitsch W, Sperr WR, Valent P. In vitro and in vivo growth-inhibitory effects of cladribine on neoplastic mast cells exhibiting the imatinib-resistant KIT mutation D816V. Exp Hematol. 2010;38:744–755. doi: 10.1016/j.exphem.2010.05.006. [PubMed] [Cross Ref]
  • Borzutzky A, Morales PS, Mezzano V, Nussbaum S, Burks W (2014) Induction of remission of frequent idiopathic anaphylaxis with rituximab. AAAAI Meeting 28.2.-04.03, abstract 91 [PubMed]
  • Boyce JA. Mast cells and eicosanoid mediators: a system of reciprocal paracrine and autocrine regulation. Immunol Rev. 2007;217:168–185. doi: 10.1111/j.1600-065X.2007.00512.x. [PubMed] [Cross Ref]
  • Breslow RG, Caiado J, Castells MC. Acetylsalicylic acid and montelukast block mast cell mediator-related symptoms during rapid desenesitization. Ann Allergy Asthma Immunol. 2009;102:155–160. doi: 10.1016/S1081-1206(10)60247-5. [PubMed] [Cross Ref]
  • Broesby-Olsen S, Kristensen T, Vestergaard H, Brixen K, Møller MB, Bindslev-Jensen C, Mastocytosis Centre Odense University Hospital (MastOUH) KIT D816V mutation burden does not correlate to clinical manifestations of indolent systemic mastocytosis. J Allergy Clin Immunol. 2013;132:723–728. doi: 10.1016/j.jaci.2013.02.019. [PubMed] [Cross Ref]
  • Broyd H, Koffer A, Assem ESK. Effect of cyclosporin-A on secretion from intact and permeabilised mast cells. Inflamm Res. 2005;54(Supplement 1):7–8. doi: 10.1007/s00011-004-0402-1. [PubMed] [Cross Ref]
  • Butterfield JH. Interferon treatment for hypereosinophilic syndromes ans systemic mastocytosis. Acta Haematol. 2005;114:26–40. doi: 10.1159/000085560. [PubMed] [Cross Ref]
  • Butterfield JH. Survey of aspirin administration in systemic mastocytosis. Prostaglandins Other Lipid Mediat. 2009;88:122–124. doi: 10.1016/j.prostaglandins.2009.01.001. [PubMed] [Cross Ref]
  • Butterfield JH, Chen D. Response of patients with indolent systemic mastocytosis to tamoxifen citrate. Leuk Res. 2016;40:10–16. doi: 10.1016/j.leukres.2015.11.004. [PubMed] [Cross Ref]
  • Butterfield JH, Weiler CR. Prevention of mast cell activation disorder-associated clinical sequelae of excessive prostaglandin D(2) production. Int Arch Allergy Immunol. 2008;147:338–343. doi: 10.1159/000144042. [PubMed] [Cross Ref]
  • Butterfield JH, Tefferi A, Kozuh GF. Successful treatment of systemic mastocytosis with high- dose interferon-alfa: long-term follow-up of a case. Leuk Res. 2005;29:131–134. doi: 10.1016/j.leukres.2004.05.003. [PubMed] [Cross Ref]
  • Cardet JC, Akin C, Lee MJ. Mastocytosis: update on pharmacotherapy and future directions. Expert Opin Pharmacother. 2013;14:2033–2045. doi: 10.1517/14656566.2013.824424. [PMC free article] [PubMed] [Cross Ref]
  • Carter MC, Robyn JA, Bressler PB, Walker JC, Shapiro GG, Metcalfe DD. Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis. J Allergy Clin Immunol. 2007;119:1550–1551. doi: 10.1016/j.jaci.2007.03.032. [PubMed] [Cross Ref]
  • Casassus P, Caillat-Vigneron N, Martin A, Simon J, Gallais V, Beaudry P, Eclache V, Laroche L, Lortholary P, Raphaël M, Guillevin L, Lortholary O. Treatment of adult systemic mastocytosis with interferon-alpha: results of a multicentre phase II trial on 20 patients. Br J Haematol. 2002;119:1090–1097. doi: 10.1046/j.1365-2141.2002.03944.x. [PubMed] [Cross Ref]
  • Caughey GH (2016) Mast cell proteases as pharmacological targets. Eur J Pharmacol 778:44–55 [PMC free article] [PubMed]
  • Chan IJ, Kasprowicz S, Tharp MD. Distinct signalling pathways for mutated KIT(V560G) and KIT(D816V) in mastocytosis. Clin Exp Dermatol. 2013;38:538–544. doi: 10.1111/ced.12000. [PubMed] [Cross Ref]
  • Chandesris MO, Damaj G, Canioni D, Brouzes C, Cabaret L, Hanssens K, Durieu I, Durupt S, Besnard S, Beyne-Rauzy O, Launay D, Schiffmann A, Niault M, Ranta D, Agape P, Faure C, Chantepie SP, Daguindau N, Bourgeet P, Dubreuil P, Lortholary O, Hermine O (2014) Treatment of advanced systemic mastocytosis with PKC412: the French compassionate use programme experience and historical comparison. ASH Meeting, abstract 3193
  • Chatterjee IB, Gupta SD, Majumder AK, Nandi BK, Subramanian N. Effect of ascorbic acid on histamine metabolism in scorbutic guinea-pigs. J Physiol. 1975;251:271–279. doi: 10.1113/jphysiol.1975.sp011091. [PubMed] [Cross Ref]
  • Church MK, Gradidge CF. Inhibition of histamine release from human lung in vitro by antihistamines and related drugs. Br J Pharmacol. 1980;69:663–667. doi: 10.1111/j.1476-5381.1980.tb07919.x. [PMC free article] [PubMed] [Cross Ref]
  • Cikler E, Ersoy Y, Cetinel S, Ercan F. The leukotriene d4 receptor antagonist, montelukast, inhibits mast cell degranulation in the dermis induced by water avoidance stress. Acta Histochem. 2009;111:112–118. doi: 10.1016/j.acthis.2008.04.006. [PubMed] [Cross Ref]
  • Clemons A, Vasiadi M, Kempuraj D, Kourelis T, Vandoros G, Theoharides TC. Amitriptyline and prochlorperazine inhibit proinflammatory mediator release from human mast cells: possible relevance to chronic fatigue syndrome. J Clin Psychopharmacol. 2011;31:385–387. doi: 10.1097/JCP.0b013e3182196e50. [PMC free article] [PubMed] [Cross Ref]
  • Cohen SS, Skovbo S, Vestergaard H, Kristensen T, Møller M, Bindslev-Jensen C, Fryzek JP, Broesby-Olsen S. Epidemiology of systemic mastocytosis in Denmark. Br J Haematol. 2014;166:521–528. doi: 10.1111/bjh.12916. [PubMed] [Cross Ref]
  • Cooper K, Young J, Wadsworth S, Cui H, diZerega GS, Rodgers KE. Reduction of post-surgical adhesion formation with tranilast. J Surg Res. 2007;141:153–161. doi: 10.1016/j.jss.2006.05.044. [PubMed] [Cross Ref]
  • Corbin AS, Griswold IJ, La Rosée P, Yee KW, Heinrich MC, Reimer CL, Druker BJ, Deininger MW. Sensitivity of oncogenic KIT mutants to the kinase inhibitors MLN518 and PD180970. Blood. 2004;104:3754–3757. doi: 10.1182/blood-2004-06-2189. [PubMed] [Cross Ref]
  • Correia O, Duarte AF, Quirino P, Azevedo R, Delgado L. Cutaneous mastocytosis: two pediatric cases treated with topical pimecrolimus. Dermatol Online J. 2010;16:8. [PubMed]
  • Damaj G, Bernit E, Ghez D, Claisse JF, Schleinitz N, Harlé JR, Canioni D, Hermine O. Thalidomide in advanced mastocytosis. Br J Haematol. 2008;141:249–253. doi: 10.1111/j.1365-2141.2008.07038.x. [PubMed] [Cross Ref]
  • De Filippis D, D’Amico A, Iuvone T. Cannabinomimetic control of mast cell mediator release: new perspective in chronic inflammation. J Neuroendocrinol. 2008;20(Suppl 1):20–25. doi: 10.1111/j.1365-2826.2008.01674.x. [PubMed] [Cross Ref]
  • Dix S, Cord M, Howard S, Coon J, Belt R, Geller R. Safety and efficacy of a continuous infusion, patient controlled anti-emetic pump to facilitate outpatient administration of high-dose chemotherapy. Bone Marrow Transplant. 1999;24:561–566. doi: 10.1038/sj.bmt.1701909. [PubMed] [Cross Ref]
  • Droogendijk HJ, Kluin-Nelemans HJC, van Doormaal JJ, Oranje AR, van de Loosdrecht AA, van Daele PLA. Imatinibmesylate in the treatment of systemic mastocytosis: a phase II trial. Cancer. 2006;107:345–351. doi: 10.1002/cncr.21996. [PubMed] [Cross Ref]
  • Dueñas-Laita A, Ruiz-Muñoz P, Armentia A, Pinacho F, Martín-Armentia B. Successful treatment of chronic drug-resistant urticaria with alprazolam. J Allergy Clin Immunol. 2009;123:504–505. doi: 10.1016/j.jaci.2008.12.005. [PubMed] [Cross Ref]
  • Duffy SM, Lawley WJ, Kaur D, Yang W, Bradding P. Inhibition of human mast cell proliferation and survival by tamoxifen in association with ion channel modulation. J Allergy Clin Immunol. 2003;112:965–972. doi: 10.1016/j.jaci.2003.07.004. [PubMed] [Cross Ref]
  • Edwards AM, Hagberg H. Oral and inhaled sodium cromoglicate in the management of systemic mastocytosis: a case report. J Med Case Rep. 2010;4:193. doi: 10.1186/1752-1947-4-193. [PMC free article] [PubMed] [Cross Ref]
  • Edwards AM, Stevens MT, Church MK. The effects of topical sodium cromoglicate on itch and flare in human skin induced by intradermal histamine: a randomised double-blind vehicle controlled intra-subject design trial. BMC Res Notes. 2011;4:47. doi: 10.1186/1756-0500-4-47. [PMC free article] [PubMed] [Cross Ref]
  • El-Agamy DS. Anti-allergic effects of nilotinib on mast cell-mediated anaphylaxis like reactions. Eur J Pharmacol. 2012;680:115–121. doi: 10.1016/j.ejphar.2012.01.039. [PubMed] [Cross Ref]
  • El-Feki G, X Zhou, LC Lau, J Pedersen, AF Walls (2011) Inhibitors of dipeptidyl peptidase I (DPPI) as mast cell stabilising agents: the contribution of DPPI in mast cell activation. J Allergy Clin Immunol 127, Suppl. – Abstracts
  • Erben P, Schwaab J, Metzgeroth G, Horny HP, Jawhar M, Sotlar K, Fabarius A, Teichmann M, Schneider S, Ernst T, Müller MC, Giehl M, Marx A, Hartmann K, Hochhaus A, Hofmann WK, Cross NC, Reiter A. The KIT D816V expressed allele burden for diagnosis and disease monitoring of systemic mastocytosis. Ann Hematol. 2014;93:81–88. doi: 10.1007/s00277-013-1964-1. [PubMed] [Cross Ref]
  • Escribano L, Akin C, Castells M, Schwartz LB. Current options in the treatment of mast cell mediator-related symptoms in mastocytosis. Inflamm Allergy Drug Targets. 2006;5:61–77. doi: 10.2174/187152806775269303. [PubMed] [Cross Ref]
  • Eskandari N, Bastan R, Peachell PT. Regulation of human skin mast cell histamine release by PDE inhibitors. Allergol Immunopathol (Madr) 2015;43:37–41. doi: 10.1016/j.aller.2013.07.011. [PubMed] [Cross Ref]
  • Estévez MD, Vieytes MR, Botana LM. Mitoxantrone induces nonimmunological histamine release from rat mast cells. Inflamm Res. 1996;45:113–117. doi: 10.1007/BF02265162. [PubMed] [Cross Ref]
  • Evans E, Gardino A, Hodous B, Davis A, Zhu J, Kohl NE, Lengauer C (2015) Blu-285, a potent and selective inhibitor for hematologic malignancies with KIT exon 17 mutations. ASH Annual Meeting: abstract 568
  • Evora PR, Simon MR. Role of nitric oxide production in anaphylaxis and its relevance for the treatment of anaphylactic hypotension with methylene blue. Ann Allergy Asthma Immunol. 2007;99:306–313. doi: 10.1016/S1081-1206(10)60545-5. [PubMed] [Cross Ref]
  • Facci L, Dal Toso R, Romanello S, Buriani A, Skaper SD, Leon A. Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc Natl Acad Sci U S A. 1995;92:3376–3380. doi: 10.1073/pnas.92.8.3376. [PubMed] [Cross Ref]
  • Finn DF, Walsh JJ. Twenty-first century mast cell stabilisers. Br J Pharmacol. 2013;170:23–37. doi: 10.1111/bph.12138. [PMC free article] [PubMed] [Cross Ref]
  • Frenkel A, Roy-Shapira A, Evgeni B, Leonid K, Borer A, Klein M. Life threatening idiopathic recurrent angioedema responding to cannabis. Case Rep Immunol. 2015;2015:780824. [PMC free article] [PubMed]
  • Friedman BS, Santiago ML, Berkebile C, Metcalfe DD. Comparison of azelastine and chlorpheniramine in the treatment of mastocytosis. J Allergy Clin Immunol. 1993;92:520–526. doi: 10.1016/0091-6749(93)90076-R. [PubMed] [Cross Ref]
  • Frieri M, Alling DW, Metcalfe DD. Comparison of the therapeutic efficacy of cromolyn sodium with that of combined chlorpheniramine and cimetidine in systemic mastocytosis. Results of a double-blind clinical trial. Am J Med. 1985;78:9–14. doi: 10.1016/0002-9343(85)90454-1. [PubMed] [Cross Ref]
  • Fujimoto T, Nishiyama T, Hanaoka K. Inhibitory effects of intravenous anesthetics on mast cell function. Anesth Analg. 2005;101:1054–1059. doi: 10.1213/01.ane.0000166955.97368.80. [PubMed] [Cross Ref]
  • Fumo G, Akin C, Metcalfe DD, Neckers L. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cells. Blood. 2004;103:1078–1084. doi: 10.1182/blood-2003-07-2477. [PubMed] [Cross Ref]
  • Galli SJ, Costa JJ. Mast-cell-leukocyte cytokine cascades in allergic inflammation. Allergy. 1995;50:851–862. doi: 10.1111/j.1398-9995.1995.tb02490.x. [PubMed] [Cross Ref]
  • Gibbs BF, Schmutzler W, Vollrath IB, Brosthardt P, Braam U, Wolff HH, Zwadlo-Klarwasser G. Ambroxol inhibits the release of histamine, leukotrienes and cytokines from human leukocytes and mast cells. Inflamm Res. 1999;48:86–93. doi: 10.1007/s000110050421. [PubMed] [Cross Ref]
  • Giraldo Castellano P, García-Erce JA, Alvarez Alegret R, Arroyo Rubio A, Mayayo Artal P, Vicente Cámara P, Rubio-Félix D, Giralt RM. Interferon alpha and systemic mastocytosis. Analysis of therapeutic efficacy in 6 cases. Rev Clin Esp. 1998;198:345–350. [PubMed]
  • Gleixner KV, Mayerhofer M, Cerny-Reiterer S, Hörmann G, Rix U, Bennett KL, Hadzijusufovic E, Meyer RA, Pickl WF, Gotlib J, Horny HP, Reiter A, Mitterbauer-Hohendanner G, Superti-Furga G, Valent P. KIT-D816V-independent oncogenic signaling in neoplastic cells in systemic mastocytosis: role of Lyn and Btk-activation and disruption by dasatinib and bosutinib. Blood. 2011;118:1885–1898. doi: 10.1182/blood-2010-06-289959. [PubMed] [Cross Ref]
  • Gleixner KV, Peter B, Blatt K, Suppan V, Reiter A, Radia D, Hadzijusufovic E, Valent P. Synergistic growth-inhibitory effects of ponatinib and midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V. Haematologica. 2013;98:1450–1457. doi: 10.3324/haematol.2012.079202. [PubMed] [Cross Ref]
  • Gotlib J, George TI, Corless C, Linder A, Ruddell A, Akin C, DeAngelo DJ, Kepten I, Lanza C, Heinemann H, Yin O, Gallagher N, Graubert T. The KIT tyrosine kinase inhibitor midostaurine (PKC412) exhibits a high response rate in aggressive systemic mastocytosis (ASM): interim results of a phase II trial. Blood. 2008;110:1039A.
  • Gotlib J, Kluin-Neelemans HC, George TI et al. (2014) Midostaurin (PKC412) demonstrates a high rate of durable responses in patients with advanced systemic mastocytosis: results from the fully accrued global phase 2 CPKC412D2201 trial. Blood;124: ASH Annual Meeting Abstracts; Abstract 636
  • Gri G, Frossi B, D’Inca F, Danelli L, Betto E, Mion F, Sibilano R, Pucillo C. Mast cell: an emerging partner in immune interaction. Front Immunol. 2012;3:120. doi: 10.3389/fimmu.2012.00120. [PMC free article] [PubMed] [Cross Ref]
  • Gromke T, Elmaagacli AH, Ditschkowski M, Hegerfeldt Y, Koldehoff M, Hlinka M, Ottinger H, Trenschel R, Beelen DW. Delayed graft-versus-mast-cell effect on systemic mastocytosis with associated clonal haematological non-mast cell lineage disease after allogeneic transplantation. Bone Marrow Transplant. 2013;48:732–733. doi: 10.1038/bmt.2012.198. [PubMed] [Cross Ref]
  • Gruson B, Lortholary O, Canioni D, Chandesris O, Lanternier F, Bruneau J, Grosbois B, Livideanu C, Larroche C, Durieu I, Barete S, Sevestre H, Diouf M, Chaby G, Marolleau JP, Dubreuil P, Hermine O, Damaj G. Thalidomide in systemic mastocytosis: results from an open-label, multicentre, phase II study. Br J Haematol. 2013;161:434–442. doi: 10.1111/bjh.12265. [PubMed] [Cross Ref]
  • Gurgel JA, Lima-Júnior RC, Rabelo CO, Pessoa BB, Brito GA, Ribeiro RA. Amitriptyline, clomipramine, and maprotiline attenuate the inflammatory response by inhibiting neutrophil migration and mast cell degranulation. Rev Bras Psiquiatr. 2013;35:387–392. doi: 10.1590/1516-4446-2012-0977. [PubMed] [Cross Ref]
  • Hadzijusufovic E, Peter B, Herrmann H, Schuch, Thaiwong T, Yuzbasiyan-Gurkan V, Pickl W, Willmann M, Valent P. Mutations in KIT predict resistance to several TKI (sorafenib, sunitinib, and masitinib) in neoplastic human and canine mast cell lines. Haematologica. 2010;95(suppl.2):357.
  • Haenisch B, Nöthen MM, Molderings GJ. Systemic mast cell activation disease: the role of molecular genetic alterations in pathogenesis, heritability and diagnostics. Immunology. 2012;137:197–205. doi: 10.1111/j.1365-2567.2012.03627.x. [PubMed] [Cross Ref]
  • Haenisch B, Fröhlich H, Herms S, Molderings GJ. Evidence for contribution of epigenetic mechanisms in the pathogenesis of systemic mast cell activation disease. Immunogenetics. 2014;66:287–297. doi: 10.1007/s00251-014-0768-3. [PubMed] [Cross Ref]
  • Hagel AF, Layritz CM, Hagel WH, Hagel HJ, Hagel E, Dauth W, Kressel J, Regnet T, Rosenberg A, Neurath MF, Molderings GJ, Raithel M. Intravenous infusion of ascorbic acid decreases serum histamine concentrations in patients with allergic and non-allergic diseases. Naunyn Schmiedeberg’s Arch Pharmacol. 2013;386:789–793. doi: 10.1007/s00210-013-0880-1. [PubMed] [Cross Ref]
  • Hagenlocher Y, Kießling K, Schäffer M, Bischoff SC, Lorentz A. Cinnamaldehyde is the main mediator of cinnamon extract in mast cell inhibition. Eur J Nutr. 2015;54:1297–1309. doi: 10.1007/s00394-014-0810-0. [PubMed] [Cross Ref]
  • Hamilton MJ, Hornick JL, Akin C, Castells MC, Greenberger NJ. Mast cell activation syndrome: a newly recognized disorder with systemic clinical manifestations. J Allergy Clin Immunol. 2011;128:147–152. doi: 10.1016/j.jaci.2011.04.037. [PubMed] [Cross Ref]
  • Hantschel O, Rix U, Schmidt U, Bürckstümmer T, Kneidinger M, Schütze G, Colinge J, Bennett KL, Ellmeier W, Valent P, Superti-Furga G. The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. Proc Natl Acad Sci U S A. 2007;104:13283–13288. doi: 10.1073/pnas.0702654104. [PubMed] [Cross Ref]
  • Harvima IT, Levi-Schaffer F, Draber P, Friedman S, Polakovicova I, Gibbs BF, Blank U, Nilsson G, Maurer M. Molecular targets on mast cells and basophils for novel therapies. J Allergy Clin Immunol. 2014;134:530–544. doi: 10.1016/j.jaci.2014.03.007. [PubMed] [Cross Ref]
  • Hauswirth AW, Simonitsch-Klupp I, Uffmann M, Koller E, Sperr WR, Lechner K, Valent P. Response to therapy with interferon alpha-2b and prednisolone in aggressive systemic mastocytosis: report of five cases and review of the literature. Leuk Res. 2004;28:249–257. doi: 10.1016/S0145-2126(03)00259-5. [PubMed] [Cross Ref]
  • Heinrich MC, Joensuu H, Demetri GD, Corless CL, Apperley J, Fletcher JA, Soulieres D, Dirnhofer S, Harlow A, Town A, McKinley A, Supple SG, Seymour J, Di Scala L, van Oosterom A, Herrmann R, Nikolova Z, McArthur AG, Imatinib Target Exploration Consortium Study B2225 Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases. Clin Cancer Res. 2008;14:2717–2725. doi: 10.1158/1078-0432.CCR-07-4575. [PubMed] [Cross Ref]
  • Hennessy B, Giles F, Cortes J, O’brien S, Ferrajoli A, Ossa G, Garcia-Manero G, Faderl S, Kantarjian H, Verstovsek S. Management of patients with systemic mastocytosis: review of M. D. Anderson Cancer Center experience. Am J Hematol. 2004;77:209–214. doi: 10.1002/ajh.20211. [PubMed] [Cross Ref]
  • Hermine O, Lortholary O, Leventhal PS, Catteau A, Soppelsa F, Baude C, Cohen-Akenine A, Palmérini F, Hanssens K, Yang Y, Sobol H, Fraytag S, Ghez D, Suarez F, Barete S, Casassus P, Sans B, Arock M, Kinet JP, Dubreuil P, Moussy A. Case-control cohort study of patients’ perceptions of disability in mastocytosis. PLoS One. 2008;3:e2266. doi: 10.1371/journal.pone.0002266. [PMC free article] [PubMed] [Cross Ref]
  • Hochhaus A, Ottmann OG, Lauber S, Hughes T, Verhoef G, Schwarer AP, Gratwohl A, Rafferty T, Resta D, Gattermann N (2006) A phase II study of nilotinib, a novel inhibitor of c-Kit, PDGFR, and Bcr-Abl, administered to patients with systemic mastocytosis. Blood 108: Abstract 2703 [ASH Annual Meeting Abstracts]
  • Hochhaus A, Baccarani M, Giles FJ, le Coutre PD, Müller MC, Reiter A, Santanastasio H, Leung M, Novick S, Kantarjian HM. Nilotinib in patients with systemic mastocytosis: analysis of the phase 2, open-label, single-arm nilotinib registration study. J Cancer Res Clin Oncol. 2015;141:2047–2060. doi: 10.1007/s00432-015-1988-0. [PMC free article] [PubMed] [Cross Ref]
  • Hoffmann K, Xifró RA, Hartweg JL, Spitzlei P, Meis K, Molderings GJ, von Kügelgen I. Inhibitory effects of benzodiazepines on the adenosine A(2B) receptor mediated secretion of interleukin-8 in human mast cells. Eur J Pharmacol. 2013;700:152–158. doi: 10.1016/j.ejphar.2012.12.003. [PubMed] [Cross Ref]
  • Horan RF, Sheffer AL, Austen KF. Cromolyn sodium in the management of systemic mastocytosis. J Allergy Clin Immunol. 1990;85:852–855. doi: 10.1016/0091-6749(90)90067-E. [PubMed] [Cross Ref]
  • Ibelgaufts H. (2016.) “Mast Cells” in COPE: cytokines and cells online pathfinder encyclopaedia, Available at (accessed March 21, 2016)
  • Jensen BM, Beaven MA, Iwaki S, Metcalfe DD, Gilfillan A. Concurrent inhibition of KIT- and FcεRI-mediated signaling: coordinated suppression of mast cell activation. J Pharmacol Exp Ther. 2008;324:128–138. doi: 10.1124/jpet.107.125237. [PMC free article] [PubMed] [Cross Ref]
  • Jin B, Ding K, Pan J. Ponatinib induces apoptosis in imatinib-resistant human mast cells by dephosphorylating mutant D816V KIT and silencing beta-catenin signaling. Mol Cancer Ther. 2014;13:1217–1230. doi: 10.1158/1535-7163.MCT-13-0397. [PubMed] [Cross Ref]
  • Johnston CS, Martin LJ, Cai X. Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis. J Am Coll Nutr. 1992;11:172–176. [PubMed]
  • Joks R, Durkin HG. Non-antibiotic properties of tetracyclines as anti-allergy and asthma drugs. Pharmacol Res. 2011;64:602–609. doi: 10.1016/j.phrs.2011.04.001. [PubMed] [Cross Ref]
  • Jones E, Koyama T, Ho RH, Kuttesch J, Shankar S, Whitlock JA, Cartwright J, Frangoul H. Safety and efficacy of a continuous infusion, patient-controlled antiemetic pump for children receiving emetogenic chemotherapy. Pediatr Blood Cancer. 2007;48:330–332. doi: 10.1002/pbc.20711. [PubMed] [Cross Ref]
  • Kaneko I, Suzuki K, Matsuo K, Kumagai H, Owada Y, Noguchi N, Hishinuma T, Ono M. Cysteinyl leukotrienes enhance the degranulation of bone marrow-derived mast cells through the autocrine mechanism. Tohoku J Exp Med. 2009;217:185–191. doi: 10.1620/tjem.217.185. [PubMed] [Cross Ref]
  • Karlberg M, Ekoff M, Labi V, Strasser A, Huang D, Nilsson G. Pro-apoptotic Bax is the major and Bak an auxiliary effector in cytokine deprivation-induced mast cell apoptosis. Cell Death Dis. 2010;1:e43. doi: 10.1038/cddis.2010.20. [PMC free article] [PubMed] [Cross Ref]
  • Karlberg M, Ekoff M, Huang DC, Mustonen P, Harvima IT, Nilsson G. The BH3-mimetic ABT-737 induces mast cell apoptosis in vitro and in vivo: potential for therapeutics. J Immunol. 2010;185:2555–2562. doi: 10.4049/jimmunol.0903656. [PubMed] [Cross Ref]
  • Katoh N, Hirano S, Yasuno H. Solitary mastocytoma treated with tranilast. J Dermatol. 1996;23:335–339. doi: 10.1111/j.1346-8138.1996.tb04026.x. [PubMed] [Cross Ref]
  • Kay LJ, Yeo WW, Peachell PT. Prostaglandin E-2 activates EP2 receptors to inhibit human lung mast cell degranulation. Br J Pharmacol. 2006;147:707–713. doi: 10.1038/sj.bjp.0706664. [PMC free article] [PubMed] [Cross Ref]
  • Kempna P, Reiter E, Arocks M, Azzi A, Zingg JM. Inhibition of HMC-1 mast cell proliferation by vitamin E. J Biol Chem. 2004;279:50700–50709. doi: 10.1074/jbc.M410800200. [PubMed] [Cross Ref]
  • Kempuraj D, Castellani ML, Petrarca C, Frydas S, Conti P, Theoharides TC, Vecchiet J. Inhibitory effect of quercetin on tryptase and inetrleukin-6 release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line. Clin Exp Med. 2006;6:150–156. doi: 10.1007/s10238-006-0114-7. [PubMed] [Cross Ref]
  • Kettelhut BV, Berkebile C, Bradley D, Metcalfe DD. A double-blind, placebo-controlled, crossover trial of ketotifen versus hydroxyzine in the treatment of pediatric mastocytosis. J Allergy Clin Immunol. 1989;83:866–870. doi: 10.1016/0091-6749(89)90097-3. [PubMed] [Cross Ref]
  • Kibsgaard L, Skjold T, Deleuran M, Vestergaard C. Omalizumab induced remission of idiopathic anaphylaxis in a patient suffering from indolent systemic mastocytosis. Acta DermVenereol. 2014;94:363–364. [PubMed]
  • Kinney SR, Carlson L, Ser-Dolansky J, Thompson C, Shah S, Gambrah A, Xing W, Schneider SS, Mathias CB. Curcumin ingestion inhibits mastocytosis and suppresses intestinal anaphylaxis in a murine model of food allergy. PLoS One. 2015;10:e0132467. doi: 10.1371/journal.pone.0132467. [PMC free article] [PubMed] [Cross Ref]
  • Kluin-Nelemans HC, Oldhoff JM, Van Doormaal JJ, Van’t Wout JW, Verhoef G, Gerrits WB, van Dobbenburgh OA, Pasmans SG, Fijnheer R. Cladribine therapy for systemic mastocytosis. Blood. 2003;102:4270–4276. doi: 10.1182/blood-2003-05-1699. [PubMed] [Cross Ref]
  • Kluin-Nelemans HC, Ferenc V, van Doormaal JJ, van Iperen C, Peters WG, Akin C, Valent P. Lenalidomide therapy in systemic mastocytosis. Leuk Res. 2009;33:e19–e22. doi: 10.1016/j.leukres.2008.06.013. [PubMed] [Cross Ref]
  • Knapper S, Cullis J, Drummond MW, Evely R, Everington T, Hoyle C, McLintock L, Poynton C, Radia D. Midostaurin a multi-targeted oral kinase inhibitor in systemic mastocytosis: report of an open-label compassionate use program in the United Kingdom. Blood. 2011;118:5145.
  • Koelink PJ, Overbeek SA, Braber S, de Kruijf P, Folkerts G, Smit MJ, Kraneveld AD. Targeting chemokine receptors in chronic inflammatory diseases: an extensive review. Pharmacol Ther. 2012;133:1–18. doi: 10.1016/j.pharmthera.2011.06.008. [PubMed] [Cross Ref]
  • Kohno M, Yamasaki S, Tybolewicz VLJ, Saito T. Rapid and large amount of autocrine IL-3 production is responsible for mast cell survival by IgE in the absence of antigen. Blood. 2005;105:2059–2065. doi: 10.1182/blood-2004-07-2639. [PubMed] [Cross Ref]
  • Kontou-Fili K, Filis CI, Voulgari C, Panayiotidis PG. Omalizumab monotherapy for bee sting and unprovoked “anaphylaxis” in a patient with systemic mastocytosis and undetectable specific IgE. Ann Allergy Asthma Immunol. 2010;104:537–539. doi: 10.1016/j.anai.2010.04.011. [PubMed] [Cross Ref]
  • Krauth MT, Majlesi Y, Sonneck K, Samorapoompichit P, Ghannadan M, Hauswirth AW, Baghestanian M, Schernthaner GH, Worda C, Muller MR, Sperr WR, Valent P. Effects of various statins on cytokine-dependent growth and IgE-dependent release of histamine in human mast cells. Allergy. 2006;61:281–288. doi: 10.1111/j.1398-9995.2006.00997.x. [PubMed] [Cross Ref]
  • Krauth MT, Böhm A, Agis H, Sonneck K, Samorapoompichit P, Florian S, Sotlar K, Valent P. Effects of the CD33-targeted drug gemtuzumab ozogamicin (Mylotarg) on growth and mediator secretion in human mast cells and blood basophils. Exp Hematol. 2007;35:108–116. doi: 10.1016/j.exphem.2006.09.008. [PubMed] [Cross Ref]
  • Krug U, Lübbert M, Büchner T. Maintenance therapy in acute myeloid leukemia revisited: will new agents rekindle an old interest? Curr Opin Hematol. 2010;17:85–90. doi: 10.1097/MOH.0b013e3283366bf4. [PubMed] [Cross Ref]
  • Kurosawa M, Amano H, Kanbe N, Igarashi Y, Nagata H, Yamashita T, Kurimoto F, Miyachi Y. Response to cyclosporin and low-dose methylprednisolone in aggressive systemic mastocytosis. J Allergy Clin Immunol. 1999;103:S412–S420. doi: 10.1016/S0091-6749(99)70156-9. [PubMed] [Cross Ref]
  • Kurzen H. (2009) Neramexane for the treatment of mast cellmediated diseases. Patent application WO2010/069595
  • Kvasnicka HM, Thiele J, Bueso-Ramos CE, Kamalanabhaiah S, Cortes JE, Kantajian H, Verstovsek S (2014) Changes in activated bone marrow macrophages and mast cells in patients with myelofibrosis following ruxolitinib therapy. ASH Meeting abstract 3184
  • Laengle UW, Markstein R, Pralet D, Seewald W, Roman D. Effect of GLC756, a novel mixed dopamine D1 receptor antagonist an dopamine D2 receptor agonist, on TNF-alpha release in vitro from activated rat mast cells. Exp Eye Res. 2006;83:1335–1339. doi: 10.1016/j.exer.2006.07.008. [PubMed] [Cross Ref]
  • Laroche M, Livideanu C, Paul C, Cantagrel A. Interferon alpha and pamidronate in osteoporosis with fracture secondary to mastocytosis. Am J Med. 2011;124:776–778. doi: 10.1016/j.amjmed.2011.02.038. [PubMed] [Cross Ref]
  • Lasho T, Tefferi A, Pardanani A. Inhibition of JAK-STAT signaling by TG101348: a novel mechanism for inhibition of KITD816V-dependent growth in mast cell leukemia cells. Leukemia. 2010;24:1378–1380. doi: 10.1038/leu.2010.109. [PubMed] [Cross Ref]
  • Lasho T, Finke C, Zblewski D et al. (2016) Concurrent activating KIT mutations in systemic mastocytosis. Br J Haematol 173:153–156 [PubMed]
  • Lau HY, Kam MF (2005) Inhibition of mast cell histamine release by specific phosphodiesterase inhibitors. Inflamm Res 54(Supplement 1):05–06 [PubMed]
  • Lechowski S, Feilhauer K, Staib L, Coëffier M, Bischoff SC, Lorentz A. Combined arginine and glutamine decrease release of de novo synthesized leukotrienes and expression of proinflammatory cytokines in activated human intestinal mast cells. Eur J Nutr. 2013;52:505–512. doi: 10.1007/s00394-012-0353-1. [PubMed] [Cross Ref]
  • Lee YS, Kim MS, Lee DH, Kwon TH, Song HH, Oh SR, do Yoon Y. Luteolin 8-C-β-fucopyranoside downregulates IL-6 expression by inhibiting MAPKs and the NF-κB signaling pathway in human monocytic cells. Pharmacol Rep. 2015;67:581–587. doi: 10.1016/j.pharep.2014.12.016. [PubMed] [Cross Ref]
  • Lieberoth S, Thomsen SF. Cutaneous and gastrointestinal symptoms in two patients with systemic mastocytosis successfully treated with omalizumab. Case Rep Med. 2015;2015:903541. [PMC free article] [PubMed]
  • Lim KH, Pardanani A, Butterfield JH, Li CY, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009;84:790–794. doi: 10.1002/ajh.21561. [PubMed] [Cross Ref]
  • Lin TY, Bear M, Du Z, Foley KP, Ying W, Barsoum J, London C. The novel HSP90 inhibitor STA-9090 exhibits activity against KIT-dependent and -independent malignant mast cell tumors. Exp Hematol. 2008;36:1266–1277. doi: 10.1016/j.exphem.2008.05.001. [PMC free article] [PubMed] [Cross Ref]
  • Lin TY, Fenger J, Murahari S, Bear MD, Kulp SK, Wang D, Chen CS, Kisseberth WC, London CA. AR-42, a novel HDAC inhibitor, exhibits biologic activity against malignant mast cell lines via down-regulation of constitutively activated KIT. Blood. 2010;115:4217–4225. doi: 10.1182/blood-2009-07-231985. [PubMed] [Cross Ref]
  • Lock AD, McNamara CJ, Rustin MH. Sustained improvement in urticaria pigmentosa and pruritus in a case of indolent systemic mastocytosis treated with cladribine. Clin Exp Dermatol. 2015;40:142–145. doi: 10.1111/ced.12488. [PubMed] [Cross Ref]
  • Lundequist A, Pejler G. Biological implications of preformed mast cell mediators. Cell Mol Life Sci. 2011;68:965–975. doi: 10.1007/s00018-010-0587-0. [PubMed] [Cross Ref]
  • Ma Z, Tovar JP, Kwong KY, Paek D. Pimecrolimus induces apoptosis of mast cells in a murine model of cutaneous mastocytosis. Int Arch Allergy Immunol. 2010;153:413–418. doi: 10.1159/000316353. [PubMed] [Cross Ref]
  • Mallet AI, Norris P, Rendell NB, Wong E, Greaves MW. The effect of disodium cromoglycate and ketotifen on the excretion of histamine and N tau-methylimidazole acetic acid in urine of patients with mastocytosis. Br J Clin Pharmacol. 1989;27:88–91. doi: 10.1111/j.1365-2125.1989.tb05339.x. [PMC free article] [PubMed] [Cross Ref]
  • Marech I, Patruno R, Zizzo N, Gadaleta C, Introna M, Zito AF, Gadaleta CD, Ranieri G. Masitinib (AB1010), from canine tumor model to human clinical development: where we are? Crit Rev Oncol Hematol. 2014;91:98–111. doi: 10.1016/j.critrevonc.2013.12.011. [PubMed] [Cross Ref]
  • Marquardt DL, Gruber HE, Walker LL. Ribavirin inhibits mast cell mediator release. J Pharmacol Exp Ther. 1987;240:145–149. [PubMed]
  • Marton I, Pósfai É, Borbényi Z, Bödör C, Papp G, Demeter J, Korom I, Varga E, Bata-Csörgő Z. Therapeutic challenge during the long-term follow-up of a patient with indolent systemic mastocytosis with extensive cutaneous involvement. Eur Rev Med Pharmacol Sci. 2015;19:1607–1609. [PubMed]
  • Matsubara S, Li G, Takeda K, Loader JE, Pine P, Masuda ES, Miyahara N, Miyahara S, Lucas JJ, Dakhama A, Gelfand EW. Inhibition of spleen tyrosine kinase prevents mast cell activation and airway hyperresponsiveness. Am J Respir Crit Care Med. 2006;173:56–63. doi: 10.1164/rccm.200503-361OC. [PMC free article] [PubMed] [Cross Ref]
  • Mattace Raso G, Russo R, Calignano A, Meli R. Palmitoylethanolamide in CNS health and disease. Pharmacol Res. 2014;86:32–41. doi: 10.1016/j.phrs.2014.05.006. [PubMed] [Cross Ref]
  • Maurer M, Magerl M, Metz M, Weller K, Siebenhaar F. Miltefosine: a novel treatment option for mast cell-mediated diseases. J Dermatolog Treat. 2013;24:244–249. doi: 10.3109/09546634.2012.671909. [PubMed] [Cross Ref]
  • McNeil BD, Pundir P, Meeker S, Han L, Undem BJ, Kulka M, Dong X. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature. 2015;519:237–241. doi: 10.1038/nature14022. [PMC free article] [PubMed] [Cross Ref]
  • Meeran SM, Ahmed A, Tollefsbol TO. Epigenetic targets of bioactive dietary components for cancer prevention and therapy. Clin Epigenetics. 2010;1:101–116. doi: 10.1007/s13148-010-0011-5. [PMC free article] [PubMed] [Cross Ref]
  • Min YD, Choi CH, Bark H, Son HY, Park HH, Lee S, Park JW, Park EK, Shin HI, Kim SH. Quercetin inhibits expression of inflammatory cytokines through attenuation of NF-kappaB and p38 MAPK in HMC-1 human mast cell line. Inflamm Res. 2007;56:210–215. doi: 10.1007/s00011-007-6172-9. [PubMed] [Cross Ref]
  • Molderings GJ. The genetic basis of mast cell activation disease—looking through a glass darkly. Crit Rev Oncol Hematol. 2015;93:75–89. doi: 10.1016/j.critrevonc.2014.09.001. [PubMed] [Cross Ref]
  • Molderings GJ (2016) Transgenerational transmission of systemic mast cell activation disease-genetic and epigenetic features. Transl Res. [PubMed]
  • Molderings GJ, Kolck UW, Scheurlen C, Brüss M, Homann J, Von Kügelgen I. Multiple novel alterations in KIT tyrosine kinase in patients with gastrointestinally pronounced systemic mast cell activation disorder. Scand J Gastroenterol. 2007;42:1045–1053. doi: 10.1080/00365520701245744. [PubMed] [Cross Ref]
  • Molderings GJ, Meis K, Kolck UW, Homann J, Frieling T. Comparative analysis of mutation of tyrosine kinase KIT in mast cells from patients with systemic mast cell activation syndrome and healthy subjects. Immunogenetics. 2010;62:721–727. doi: 10.1007/s00251-010-0474-8. [PubMed] [Cross Ref]
  • Molderings GJ, Brettner S, Homann J, Afrin LB. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. J Hematol Oncol. 2011;4:10. doi: 10.1186/1756-8722-4-10. [PMC free article] [PubMed] [Cross Ref]
  • Molderings GJ, Raithel M, Kratz F, Azemar M, Haenisch B, Harzer S, Homann J. Omalizumab treatment of systemic mast cell activation disease: experiences from four cases. Intern Med. 2011;50:1–5. doi: 10.2169/internalmedicine.50.4640. [PubMed] [Cross Ref]
  • Molderings GJ, Haenisch B, Bogdanow M, Fimmers R, Nöthen MM. Familial occurrence of systemic mast cell activation disease. PLoS One. 2013;8:e76241. doi: 10.1371/journal.pone.0076241. [PMC free article] [PubMed] [Cross Ref]
  • Molderings GJ, Haenisch B, Homann J, Wilhelm T, Huber M. Neue Angriffspunkte der 1-4-Benzodiazepine in der mastzelspezifischen immunsuppressiven Therapie der sytemischen Mastzellüberaktivitätserkrankung. Gastroenterologe. 2013;8:170.
  • Molderings GJ, Homann J, Brettner S, Raithel M, Frieling T. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. Dtsch Med Wochenschr. 2014;139:1523–1534. doi: 10.1055/s-0034-1370055. [PubMed] [Cross Ref]
  • Moon PD, Lee BH, Jeong HJ, An HJ, Park SJ, Kim HR, Ko SG, Um JY, Hong SH, Kim HM. Use of scopoletin to inhibit the production of inflammatory cytokines through inhibition of the IkB/NF-kB signal cascade in the human mast cell line HMC-1. Eur J Pharmacol. 2007;555:218–225. doi: 10.1016/j.ejphar.2006.10.021. [PubMed] [Cross Ref]
  • Mousli M, Hugli TE, Landry Y, Bronner C. Peptidergic pathway in human skin and rat peritoneal mast cell activation. Immunopharmacology. 1994;27:1–11. doi: 10.1016/0162-3109(94)90002-7. [PubMed] [Cross Ref]
  • Moussy A, Kinet JP (2014) Treatment of mastocytosis with masitinib. US Patent Application
  • Mühlenberg T, Zhang Y, Wagner AJ, Grabellus F, Bradner J, Taeger G, Lang H, Taguchi T, Schuler M, Fletcher JA, Bauer S. Inhibitors of deacetylases suppress oncogenic KIT signaling, acetylate HSP90, and induce apoptosis in gastrointestinal stromal tumors. Cancer Res. 2009;69:6941–6950. doi: 10.1158/0008-5472.CAN-08-4004. [PMC free article] [PubMed] [Cross Ref]
  • Nader MA. Inhibition of anaphylaxis like reaction and mast cell activation by sitagliptin. Int Immunopharmacol. 2011;11:1052–1056. doi: 10.1016/j.intimp.2011.02.026. [PubMed] [Cross Ref]
  • Nakamura R, Chakrabarti S, Akin C, Robyn J, Bahceci E, Greene A, Childs R, Dunbar CE, Metcalfe DD, Barrett AJ. A pilot study of nonmyeloablative allogeneic hematopoietic stem cell transplant for advanced systemic mastocytosis. Bone Marrow Transplant. 2006;37:353–358. doi: 10.1038/sj.bmt.1705245. [PubMed] [Cross Ref]
  • Nolte H, Stahl Skov P. Inhibition of basophil histamine release by methotrexate. Agents Actions. 1988;23:173–176. doi: 10.1007/BF02142532. [PubMed] [Cross Ref]
  • Nurmatov UB, Rhatigan E, Simons FE, Sheikh A. H1-antihistamines for primary mast cell activation syndromes: a systematic review. Allergy. 2015;70:1052–1061. doi: 10.1111/all.12672. [PubMed] [Cross Ref]
  • Oppong E, Flink N, Cato AC. Molecular mechanisms of glucocorticoid action in mast cells. Mol Cell Endocrinol. 2013;380:119–126. doi: 10.1016/j.mce.2013.05.014. [PubMed] [Cross Ref]
  • Otani IM, Bhagat M, Newbury RO, Dohil R, Broide DH, Aceves SS. The effect of anti-IL-5 therapy on esophageal mastocytosis in pediatric eosinophilic esophagitis. J Allergy Clin Immunol. 2012;129:AB202. doi: 10.1016/j.jaci.2011.12.180. [Cross Ref]
  • Paez P, Ryan J, Taruselli M, Ndaw V. Fluvastatin elicits apoptosis in primary and transformed mast cells (INC6P.305) J Immunol. 2015;194(Suppl. 1):197.7.
  • Pagano L, Valentini CG, Caira M, Rondoni M, Van Lint MT, Candoni A, Allione B, Cattaneo C, Marbello L, Caramatti C, Pogliani EM, Iannitto E, Giona F, Ferrara F, Invernizzi R, Fanci R, Lunghi M, Fianchi L, Sanpaolo G, Stefani PM, Pulsoni A, Martinelli G, Leone G, Musto P. Advanced mast cell disease: an Italian Hematological Multicenter experience. Int J Hematol. 2008;88:483–488. doi: 10.1007/s12185-008-0166-4. [PubMed] [Cross Ref]
  • Paivandy A, Calounova G, Zarnegar B, Ohrvik H, Melo FR, Pejler G. Mefloquine, an anti-malaria agent, causes reactive oxygen species-dependent cell death in mast cells via a secretory granule-mediated pathway. Pharmacol Res Perspect. 2014;2:e00066. doi: 10.1002/prp2.66. [PMC free article] [PubMed] [Cross Ref]
  • Pan J, Quintas-Cardama A, Kantarjian HM, Akin C, Manshouri T, Lamb P, Cortes JE, Tefferi A, Giles FJ, Verstovsek S. EXEL-0862, a novel tyrosine kinase inhibitor, induces apoptosis in vitro and ex vivo in human mast cells expressing the KIT D816V mutation. Blood. 2007;109:315–322. doi: 10.1182/blood-2006-04-013805. [PubMed] [Cross Ref]
  • Papaetis GS, Syrigos KN. Sunitinib: a multitargeted receptor tyrosine kinase inhibitor in the era of molecular cancer therapies. BioDrugs. 2009;23:377–389. doi: 10.2165/11318860-000000000-00000. [PubMed] [Cross Ref]
  • Papayannidis C, Soverini S, Benedittis CD, Abbenante MC, Sartor C, Iacobucci I, Baldazzi C, Ottaviani E, Ferrari A, Guadagnuolo V, Conficoni A, Paolini S, Parisi S, Frabetti F, Piccari S, Grilli S, Lani E, Martinelli G. PKC412 (midostaurin) is safe and highly effective in systemic mastocytosis patients: follow up of a single-center Italian compassionate use. Cancer Res. 2014;74:746. doi: 10.1158/1538-7445.AM2014-746. [Cross Ref]
  • Pardanani A. Systemic mastocytosis in adults: 2013 update on diagnosis, risk stratification, and management. Am J Hematol. 2013;88:612–624. doi: 10.1002/ajh.23459. [PubMed] [Cross Ref]
  • Pardanani A, Elliott M, Reeder T, Li CY, Baxter EJ, Cross NC, Tefferi A. Imatinib for systemic mast-cell disease. Lancet. 2003;362:535–536. doi: 10.1016/S0140-6736(03)14115-3. [PubMed] [Cross Ref]
  • Pardanani A, Hoffbrand AV, Butterfield JH, Tefferi A. Treatment of systemic mast cell disease with 2-chlorodeoxyadenosine. Leuk Res. 2004;28:127–131. doi: 10.1016/S0145-2126(03)00185-1. [PubMed] [Cross Ref]
  • Parikh SA, Kantarjian HM, Richie MA, Cortes JE, Verstovsek S. Experience with everolimus (RAD001), an oral mammalian target of rapamycin inhibitor, in patients with systemic mastocytosis. Leuk Lymphoma. 2010;51:269–274. doi: 10.3109/10428190903486220. [PMC free article] [PubMed] [Cross Ref]
  • Park TH. The effects of botulinum toxin A on mast cell activity: preliminary results. Burns. 2013;39:816–817. doi: 10.1016/j.burns.2012.07.031. [PubMed] [Cross Ref]
  • Paul C, Sans B, Suarez F, Casassus P, Barete S, Lanternier F, Grandpeix-Guyodo C, Dubreuil P, Palmérini F, Mansfield CD, Gineste P, Moussy A, Hermine O, Lortholary O. Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study. Am J Hematol. 2010;85:921–925. doi: 10.1002/ajh.21894. [PubMed] [Cross Ref]
  • Peter B, Hadzijusufovic E, Blatt K, Gleixner KV, Pickl WF, Thaiwong T, Yuzbasiyan-Gurkan V, Willmann M, Valent P. KIT polymorphisms and mutations determine responses of neoplastic mast cells to bafetinib (INNO-406) Exp Hematol. 2010;38:782–791. doi: 10.1016/j.exphem.2010.05.004. [PubMed] [Cross Ref]
  • Peter B, Gleixner KV, Cerny-Reiterer S, Herrmann H, Winter V, Hadzijusufovic E, Ferenc V, Schuch K, Mirkina I, Horny HP, Pickl WF, Mullauer L, Willmann M, Valent P. Polo-like kinase-1 as novel target in neoplastic mast cells: demonstration of growth-inhibitory effects of siRNA and the Polo-like kinase-1 targeting drug BI 2536. Haematologica. 2011;96(5):672–680. doi: 10.3324/haematol.2010.031328. [PubMed] [Cross Ref]
  • Picard M, Giavina-Bianchi P, Mezzano V, Castells M. Expanding spectrum of mast cell activation disorders: monoclonal and idiopathic mast cell activation syndromes. Clin Ther. 2013;35:548–562. doi: 10.1016/j.clinthera.2013.04.001. [PubMed] [Cross Ref]
  • Purtill D, Cooney J, Sinniah R, Carnley B, Cull G, Augustson B, Cannell P. Dasatinib therapy for systemic mastocytosis: four cases. Eur J Haematol. 2008;80:456–458. doi: 10.1111/j.1600-0609.2008.01048.x. [PubMed] [Cross Ref]
  • Quintás-Cardama A, Jain N, Verstovsek S. Advances and controversies in the diagnosis, pathogenesis, and treatment of systemic mastocytosis. Cancer. 2011;117:5439–5449. doi: 10.1002/cncr.26256. [PMC free article] [PubMed] [Cross Ref]
  • Quintás-Cardama A, Sever M, Cortes J, Kantarjian H, Verstovsek S. Bone marrow mast cell burden and serum tryptase level as markers of response in patients with systemic mastocytosis. Leuk Lymphoma. 2013;54:1959–1964. doi: 10.3109/10428194.2012.763121. [PMC free article] [PubMed] [Cross Ref]
  • Radojković M, Ristić S, Colović N, Terzić T, Colović M. Response to cladribine in patient with systemic mastocytosis. Vojnosanit Pregl. 2011;68:444–446. doi: 10.2298/VSP1105444R. [PubMed] [Cross Ref]
  • Randall N, Courville EL, Baughn L, Afrin L, Ustun C. Bosutinib, a lyn/btk inhibiting tyrosine kinase inhibitor, is ineffective in advanced systemic mastocytosis. Am J Hematol. 2015;90:E74. doi: 10.1002/ajh.23942. [PubMed] [Cross Ref]
  • Ritter M, El-Nour H, Hedblad MA, Butterfield JH, Beck O, Stephanson N, Holst M, Giscombe R, Azmitia EC, Nordlind K. Serotonin and its 5-HT1 receptor in human mastocytosis. Immunopharmacol Immunotoxicol. 2012;34:679–685. doi: 10.3109/08923973.2011.651222. [PubMed] [Cross Ref]
  • Rodrigo L, Perez-Martinez I, Lucendo AJ. Urticaria pigmentosa in a female patient wth celiac disease: response to a gluten-free diet. Allergol Immunopathol (Madr) 2013;41:128–130. doi: 10.1016/j.aller.2012.01.005. [PubMed] [Cross Ref]
  • Rodrigues JM, Pazin Filho A, Rodrigues AJ, Vicente WV, Evora PR. Methylene blue for clinical anaphylaxis treatment: a case report. Sao Paulo Med J. 2007;125:60–62. doi: 10.1590/S1516-31802007000100012. [PubMed] [Cross Ref]
  • Rodriguez T, Pfeffer M, Levy BD, Castells M. Lipid mediators in cutaneous and systemic mastocytosis and the impact of 5-LO inhibition. J Allergy Clin Immunol. 2011;127(Suppl):AB132.
  • Rosen H, Goetzl EJ. Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network. Nat Rev Immunol. 2005;5:560–570. doi: 10.1038/nri1650. [PubMed] [Cross Ref]
  • Ruano I, Gargini R, Izquierdo M. Combination of KIT gene silencing and tocopherol succinate may offer improved therapeutic approaches for human mastocytosis. Br J Haematol. 2010;148:59–68. doi: 10.1111/j.1365-2141.2009.07918.x. [PubMed] [Cross Ref]
  • Sagi L, Solomon M, Baum S, Lyakhovitsky A, Trau H, Barzilai A. Evidence for methotrexate as a useful treatment for steroid-dependent chronic urticaria. Acta Derm Venereol. 2011;91:303–306. doi: 10.2340/00015555-1080. [PubMed] [Cross Ref]
  • Sandler C, Nurmi K, Lindstedt KA, Sorsa T, Golub LM, Kovanen PT, Eklund KK. Chemically modified tetracyclines induce apoptosis in cultured mast cells. Int Immunohistopharmacol. 2005;5:1611–1621. doi: 10.1016/j.intimp.2005.04.013. [PubMed] [Cross Ref]
  • Schittenhelm MM, Akmut F, Illing B, Frey J, Schuster K, Ramachandran A, Kanz L, Kampa-Schittenhelm KM (2014) Gain-of-function KIT mutations sensitize the mutant isoform to the type I tyrosine kinase inhibitor crenolanib: a rationale for the therapeutic use in systemic mastocytosis (SM) and core binding factor leukemias (CBFL). ASH-Meeting abstract 2230
  • Seifert R. How do basic secretagogues activate mast cells? Naunyn Schmiedeberg’s Arch Pharmacol. 2015;388:279–281. doi: 10.1007/s00210-015-1093-6. [PubMed] [Cross Ref]
  • Shimoda T, Liang Z, Suzuki H, Kawana S. Inhibitory effects of antipsychotic and anxiolytic agents on stress-induced degranulation of mouse dermal mast cells. Clin Exp Dermatol. 2010;35:531–536. doi: 10.1111/j.1365-2230.2009.03650.x. [PubMed] [Cross Ref]
  • Sido B, Dumoulin FL, Homann J, Hertfelder HJ, Bollmann M, Molderings GJ. Surgical interventions in patients with mast cell activation disease. Aspects relevant for surgery using the example of a cholecystectomy. Chirurg. 2014;85:327–333. doi: 10.1007/s00104-013-2642-5. [PubMed] [Cross Ref]
  • Siebenhaar F, Förtsch A, Krause K, Weller K, Metz M, Magerl M, Martus P, Church MK, Maurer M. Rupatadine improves quality of life in mastocytosis: a randomized, double-blind, placebo-controlled trial. Allergy. 2013;68:949–952. doi: 10.1111/all.12159. [PubMed] [Cross Ref]
  • Simhadri VR, Andersen JF, Calvo E, Choi SC, Coligan JE, Borrego F. Human CD300a binds to phosphatidylethanolamine and phosphatidylserine, and modulates the phagocytosis of dead cells. Blood. 2012;119:2799–2809. doi: 10.1182/blood-2011-08-372425. [PubMed] [Cross Ref]
  • Simon J, Lortholary O, Caillat-Vigneron N, Raphael M, Martin A, Briere J, Barete S, Hermine O, Casussus P. Interest of interferon alpha in systemic mastocytosis. The french experience and review of the literature. Pathol Biol. 2004;52:294–299. doi: 10.1016/j.patbio.2004.04.012. [PubMed] [Cross Ref]
  • Soter NA, Austen KF, Wasserman SI, Soter NA, Austen KF, Wasserman SI. Oral disodium cromoglycate in the treatment of systemic mastocytosis. N Engl J Med. 1979;301:465–469. doi: 10.1056/NEJM197908303010903. [PubMed] [Cross Ref]
  • Spirkoski J, Melo FR, Grujic M, Calounova G, Lundequist A, Wernersson S, Pejler G. Mast cell apoptosis induced by siramesine, a sigma-2 receptor agonist. Biochem Pharmacol. 2012;84:1671–1680. doi: 10.1016/j.bcp.2012.09.028. [PubMed] [Cross Ref]
  • Spyridonidis A, Thomas AK, Bertz H, Zeiser R, Schmitt-Graff A, Lindemann A, Waller CF, Finke J. Evidence for a graft-versus-mast-cell effect after allogeneic bone marrow transplantation. Bone Marrow Transplant. 2004;34:515–519. doi: 10.1038/sj.bmt.1704627. [PubMed] [Cross Ref]
  • Strati P, Kantarjian H, Ravandi F, Nazha A, Borthakur G, Daver N, Kadia T, Estrov Z, Garcia-Manero G, Konopleva M, Rajkhowa T, Durand M, Andreeff M, Levis M, Cortes J. Phase I/II trial of the combination of midostaurin (PKC412) and 5-azacytidine for patients with acute myeloid leukemia and myelodysplastic syndrome. Am J Hematol. 2015;90:276–281. doi: 10.1002/ajh.23924. [PMC free article] [PubMed] [Cross Ref]
  • Suzuki-Nishimura T, Sano T, Uchida MK. Effects of benzodiazepines on serotonin release from rat mast cells. Eur J Pharmacol. 1989;167:75–85. doi: 10.1016/0014-2999(89)90749-8. [PubMed] [Cross Ref]
  • Tachibana M, Wada K, Katayama K, Kamisaki Y, Maeyama K, Kadowaki T, Blumberg RS, Nakajima A. Activation of peroxisome proliferator-activated receptor gamma suppresses mast cell maturation involved in allergic diseases. Allergy. 2008;63:1136–1147. doi: 10.1111/j.1398-9995.2008.01677.x. [PMC free article] [PubMed] [Cross Ref]
  • Tanaka A, Konno M, Muto S, Kambe N, Morii E, Nakahata T, Itai A, Matsuda H. A novel NF-kappa B inhibitor, IMD-0354, suppresses neoplastic proliferation of human mast cells with constitutively activated c-Kit receptors. Blood. 2005;105:2324–2331. doi: 10.1182/blood-2004-08-3247. [PubMed] [Cross Ref]
  • Tang C, Lan C, Wang C, Liu R. Amelioration of the development of multiple organ dysfunction syndrome by somatostatin via suppression of intestinal mucosal mast cells. Shock. 2005;23:470–475. doi: 10.1097/01.shk.0000160522.29482.df. [PubMed] [Cross Ref]
  • Tanimoto A, Ogawa Y, Oki C, Kimoto Y, Nozawa K, Amano W, Noji S, Shiozaki M, Matsuo A, Shinozaki Y, Matsushita M. Pharmacological properties of JTE-052: a novel potent JAK inhibitor that suppresses various inflammatory responses in vitro and in vivo. Inflamm Res. 2015;64:41–51. doi: 10.1007/s00011-014-0782-9. [PMC free article] [PubMed] [Cross Ref]
  • Tefferi A, Li CY, Butterfield JH, Hoagland HC. Treatment of systemic mast-cell disease with cladribine. N Engl J Med. 2001;344:307–309. doi: 10.1056/NEJM200101253440415. [PubMed] [Cross Ref]
  • Tolar J, Tope WD, Neglia JP. Leukotriene-receptor inhibition for the treatment of systemic mastocytosis. N Engl J Med. 2004;350:735–736. doi: 10.1056/NEJM200402123500723. [PubMed] [Cross Ref]
  • Topar G, Staudacher C, Geisen F, Gabl C, Fend F, Herold M, Greil R, Fritsch P, Sepp N. Urticaria pigmentosa: a clinical, hematopathologic, and serologic study of 30 adults. Am J Clin Pathol. 1998;109:279–285. doi: 10.1093/ajcp/109.3.279. [PubMed] [Cross Ref]
  • Trojan TD, Khan DA. Calcineurin inhibitors in chronic urticaria. Curr Opin Allergy Clin Immunol. 2012;12:412–420. doi: 10.1097/ACI.0b013e32835571f6. [PubMed] [Cross Ref]
  • Turner PJ, Kemp AS, Rogers M, Mehr S. Refractory symptoms successfully treated with leukotriene inhibition in a child with systemic mastocytosis. Pediatr Dermatol. 2012;29:222–223. doi: 10.1111/j.1525-1470.2011.01576.x. [PubMed] [Cross Ref]
  • Uchida K, Mitsui M, Kawakishi S. Monooxygenation of N-acetylhistamine mediated by L-ascorbate. Biochim Biophys Acta. 1989;991:377–379. doi: 10.1016/0304-4165(89)90131-1. [PubMed] [Cross Ref]
  • Ustun C, Reiter A, Scott BL, Nakamura R, Damaj G, Kreil S, Shanley R, Hogan WJ, Perales MA, Shore T, Baurmann H, Stuart R, Gruhn B, Doubek M, Hsu JW, Tholouli E, Gromke T, Godley LA, Pagano L, Gilman A, Wagner EM, Shwayder T, Bornhäuser M, Papadopoulos EB, Böhm A, Vercellotti G, Van Lint MT, Schmid C, Rabitsch W, Pullarkat V, Legrand F, Yakoub-Agha I, Saber W, Barrett J, Hermine O, Hagglund H, Sperr WR, Popat U, Alyea EP, Devine S, Deeg HJ, Weisdorf D, Akin C, Valent P. Hematopoietic stem-cell transplantation for advanced systemic mastocytosis. J Clin Oncol. 2014;32:3264–3274. doi: 10.1200/JCO.2014.55.2018. [PMC free article] [PubMed] [Cross Ref]
  • Vaali K, Lappalainen J, Lin AH, Mäyränpää MI, Kovanen PT, Berstad A, Eklund KK. Imatinib mesylate alleviates diarrhea in a mouse model of intestinal allergy. Neurogastroenterol Motil. 2012;24:e325–e335. doi: 10.1111/j.1365-2982.2012.01941.x. [PubMed] [Cross Ref]
  • Valent P, Horny HP, Escribano L, Longley BJ, Li CY, Schwartz LB, Marone G, Nuñez R, Akin C, Sotlar K, Sperr WR, Wolff K, Brunning RD, Parwaresch RM, Austen KF, Lennert K, Metcalfe DD, Vardiman JW, Bennett JM. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res. 2001;25:603–625. doi: 10.1016/S0145-2126(01)00038-8. [PubMed] [Cross Ref]
  • Valent P, Akin C, Escribano L, Födinger M, Hartmann K, Brockow K, Castells M, Sperr WR, Kluin-Nelemans HC, Hamdy NA, Lortholary O, Robyn J, van Doormaal J, Sotlar K, Hauswirth AW, Arock M, Hermine O, Hellmann A, Triggiani M, Niedoszytko M, Schwartz LB, Orfao A, Horny HP, Metcalfe DD. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Investig. 2007;37:435–453. doi: 10.1111/j.1365-2362.2007.01807.x. [PubMed] [Cross Ref]
  • Valent P, Sperr WR, Akin C. How I treat patients with advanced systemic mastocytosis. Blood. 2010;116:5812–5817. doi: 10.1182/blood-2010-08-292144. [PubMed] [Cross Ref]
  • Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, Castells M, Escribano L, Hartmann K, Lieberman P, Nedoszytko B, Orfao A, Schwartz LB, Sotlar K, Sperr WR, Triggiani M, Valenta R, Horny HP, Metcalfe DD. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157:215–225. doi: 10.1159/000328760. [PMC free article] [PubMed] [Cross Ref]
  • van Doormaal JJ, Idema IG, de Monchy JG, Breukelman H, Keyzer JJ, Doorenbos H. Effects of isoprenaline and terbutaline on urinary excretion of histamine and its two main metabolites in systemic mastocytosis. Agents Actions. 1986;18:269–272. doi: 10.1007/BF01988039. [PubMed] [Cross Ref]
  • van Doormaal JJ, Arends S, Brunekreeft KL, et al. Prevalence of indolent systemic mastocytosis in a Dutch region. J Allergy Clin Immunol. 2013;131:1429–1431. doi: 10.1016/j.jaci.2012.10.015. [PubMed] [Cross Ref]
  • Vega-Ruiz A, Cortes JE, Sever M, Manshouri T, Quintás-Cardama A, Luthra R, Kantarjian HM, Verstovsek S. Phase II study of imatinibmesylate as therapy for patients with systemic mastocytosis. Leuk Res. 2009;33:1481–1484. doi: 10.1016/j.leukres.2008.12.020. [PMC free article] [PubMed] [Cross Ref]
  • Verstovsek S, Tefferi A, Cortes J, O’Brien S, Garcia-Manero G, Pardanani A, Akin C, Faderl S, Manshouri T, Thomas D, Kantarjian H. Phase II study of dasatinib in Philadelphia chromosome-negative acute and chronic myeloid diseases, including systemic mastocytosis. Clin Cancer Res. 2008;14:3906–3915. doi: 10.1158/1078-0432.CCR-08-0366. [PMC free article] [PubMed] [Cross Ref]
  • Vrugt B, Wilson S, Bron A, Shute J, Holgate ST, Djukanovic R, Aalbers R. Low-dose methotrexate treatment in severe glucocorticoid-dependent asthma: effect on mucosal inflammation and in vitro sensitivity to glucocorticoids of mitogen-induced T-cell proliferation. Eur Respir J. 2000;15:478–485. doi: 10.1034/j.1399-3003.2000.15.09.x. [PubMed] [Cross Ref]
  • Welch EA, Alper JC, Bogaars H, Farrell DS. Treatment of bullous mastocytosis with disodium cromoglycate. J Am Acad Dermatol. 1983;9:349–353. doi: 10.1016/S0190-9622(83)70140-4. [PubMed] [Cross Ref]
  • Weller K, Artuc M, Jennings G, Friedrichson T, Guhl S, Dos Santos RV, Sünder C, Zuberbier T, Maurer M. Miltefosine inhibits human mast cell activation and mediator release both in vitro and in vivo. J Invest Dermatol. 2009;129:496–498. doi: 10.1038/jid.2008.248. [PubMed] [Cross Ref]
  • Weng Z, Zhang B, Asadi S, Sismanopoulos N, Butcher A, Fu X, Katsarou-Katsari A, Antoniou C, Theoharides TC. Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans. PLoS One. 2012;7:e33805. doi: 10.1371/journal.pone.0033805. [PMC free article] [PubMed] [Cross Ref]
  • Weng Z, Patel AB, Panagiotidou S, Theoharides TC (2015) The novel flavone tetramethoxyluteolin is a potent inhibitor of human mast cells. J Allergy Clin Immunol 135:1044–1052 [PMC free article] [PubMed]
  • Worobec AS, Kirshenbaum AS, Schwartz LB, Metcalfe DD. Treatment of three patients with systemic mastocytosis with interferon alpha-2b. Leuk Lymphoma. 1996;22:501–508. doi: 10.3109/10428199609054789. [PubMed] [Cross Ref]
  • Yacoub A, Prochaska L. Ruxolitinib improves symptoms and quality of life in a patient with systemic mastocytosis. Biomark Res. 2016;4:2. doi: 10.1186/s40364-016-0056-5. [PMC free article] [PubMed] [Cross Ref]
  • Yamaguchi S, Okada Y, Matsunaga Y, Nambu F. Effect of ONO-4053 on FcεRI stimulated mast cell activation. J Allergy Clin Immunol. 2016;137:AB77. doi: 10.1016/j.jaci.2015.12.260. [Cross Ref]
  • Yamaki K, Yoshino S. Tyrosine kinase inhibitor sunitinib relieves systemic and oral antigen-induced anaphylaxes in mice. Allergy. 2012;67:114–122. doi: 10.1111/j.1398-9995.2011.02717.x. [PubMed] [Cross Ref]
  • Yang Y, Lu JY, Wu X, Summer S, Whoriskey J, Saris C, Reagan JD. G-protein-coupled receptor 35 is a target of the asthma drugs cromolyn disodium and nedocromil sodium. Pharmacology. 2010;86:1–5. doi: 10.1159/000314164. [PubMed] [Cross Ref]
  • Yoshida C, Takeuchi M, Tsuchiyama J, Sadahira Y. Successful treatment of KIT D816V-positive, imatinib-resistant systemic mastocytosis with interferon-alpha. Intern Med. 2009;48:1973–1978. doi: 10.2169/internalmedicine.48.2294. [PubMed] [Cross Ref]
  • Zachariae H, Herlin T, Larsen PO. Oral disodium cromoglycate in mastocytosis. Acta Derm Venereol. 1981;61:272–273. [PubMed]
  • Zen M, Canova M, Campana C, Bettio S, Nalotto L, Rampudda M, Ramonda R, Iaccarino L, Doria A. The kaleidoscope of glucorticoid effects on immune system. Autoimmun Rev. 2011;10:305–310. doi: 10.1016/j.autrev.2010.11.009. [PubMed] [Cross Ref]
  • Zhang T, Finn DF, Barlow JW, Walsh JJ (2016) Mast cell stabilisers. Eur J Pharmacol 778:158–168 [PubMed]

Articles from Springer Open Choice are provided here courtesy of Springer