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1.  Interferon-β-induced pulmonary sarcoidosis in a 30-year-old woman treated for multiple sclerosis: a case report 
With the increasing use of recombinant α and β interferon therapy for the treatment of various disorders, cases of interferon-associated sarcoidosis have been reported in the literature. The majority of these have been cases of interferon-α-induced sarcoidosis. We present the first case, to the best of our knowledge, of interferon-induced pulmonary sarcoidosis in a patient whose multiple sclerosis was treated with interferon-β.
Case presentation
We present the case of a 30-year-old Caucasian woman who presented with unusually persistent bilateral areas of lung consolidation on serial radiographs. Pulmonary sarcoidosis was diagnosed on transbronchial lung biopsy five months after the initiation of treatment with interferon-β for multiple sclerosis.
Sarcoidosis should be considered in the differential diagnosis of a patient who develops clinical or radiological pulmonary disease while undergoing interferon therapy. It is important to note that interferon-induced sarcoidosis, though usually seen in cases with interferon-α, can occur with interferon-β. Neurologists managing patients with multiple sclerosis should be aware of this association between interferon-β and sarcoidosis and promptly refer patients developing respiratory symptoms for further investigation.
PMCID: PMC3492064  PMID: 23043877
2.  Interferon-alpha-induced sarcoidosis in a patient being treated for hepatitis C 
Patient: Female, 43
Final Diagnosis: —
Symptoms: Diarrhea • generalized weakness • headache • lightheadedness • nausea • rash • short of breath • vomiting
Medication: —
Clinical Procedure: —
Specialty: Pulmonology
Rare diseae
IFN-alpha-2b in combination with ribavirin is now the standard of care for the treatment of hepatitis C. Sarcoidosis is a chronic multisystem granulomatous disorder characterized by noncaseating granulomas in the involved organs. The pathologic hallmark of sarcoidosis is the presence of noncaseating granulomas in the interstitium that typically involve the lymphatics.
Case Report:
A 43-year-old woman presented to our care with 2-week history of nausea, vomiting, diarrhea, shortness of breath, migraine headache, maculopapular rash, generalized weakness, and lightheadedness. She had been treated for hepatitis C with telaprevir, ribavirin, and interferon-alpha-2b for 6 months. Chest radiograph showed bilateral diffuse prominence of bronchovascular markings. CT of the chest revealed bilateral diffuse centrilobular nodules with associated intralobular septal thickening, thickening of the central peribronchovascular interstitium, nodularity of the major fissures, and mediastinal lymphadenopathy. These findings were suspicious for atypical pulmonary sarcoidosis, possibly interferon-induced. The pathology of the mediastinal lymph node biopsy revealed noncaseating granulomatous inflammation consistent with the diagnosis of pulmonary sarcoidosis. Pathology of the skin punch biopsy showed giant-cell granulomatous inflammation without necrosis. The patient was started on prednisone 40 mg daily with a steroid tapering course for 8 weeks.
The management of IFN-induced sarcoidosis includes the discontinuation of IFN therapy with or without the administration of systemic corticosteroids. With the increasing prevalence of HCV in the United States, it is likely that more IFN-alpha-induced sarcoidosis will be encountered by clinicians.
PMCID: PMC4043539  PMID: 24900166
Hepatitis C; Interferons - adverse effects; Sarcoidosis - chemically induced
3.  Sarcoidosis with Multi-organ Involvement Presenting as Ventricular Tachycardia 
Sarcoidosis is a granulomatous disease which can affect any organ, but most commonly presents with pulmonary manifestations. We present an unusual case of sarcoidosis with multiorgan involvement which initially manifested as ventricular tachycardia; the patient was subsequently found to have extensive cardiac, respiratory, skin, and hepatic involvement.
Case Report:
An otherwise healthy 35-year-old African American soldier presented to emergency care with hypotension and tachycardia greater than 200 beats per minute. He was found to be in sustained ventricular tachycardia with a pulse. Defibrillation was performed, the patient was loaded with amiodarone, and hospitalized. Cardiac catheterization showed no evidence of atherosclerotic coronary artery disease. A cardiac MRI revealed high density lesions in the lateral wall and apex, and diffusely decreased left ventricular wall motion. An implantable cardiac defibrillator (ICD) was placed. Further questioning revealed a six month history of twenty pounds weight loss, persistent nasal congestion, and subcutaneous nodules. Biopsy of two subcutaneous nodules from the left upper extremity and nasal mucosa biopsy demonstrated noncaseating granulomas. His evaluation was notable for a mixed pattern hepatic injury, normocytic anemia, elevated lactate dehydrogenase, and a CT chest showing hilar and mediastinal adenopathy with multiple pulmonary nodules. Sarcoidosis was suspected and additional testing for HIV, EBV, vasculitis, lymphoma, fungal infection, and mycobacterial infection was negative. Pulmonary function tests showed normal basic spirometry and DLCO. Transthoracic echocardiogram demonstrated normal ejection fraction, and an 8mm cystic structure partially incorporated in the left ventricular wall. This was suspected to be a granulomatous accumulation. Sestamibi imaging showed a dense defect involving the apex and a medium sized, moderate severity, inferior wall defect consistent with an infiltrative process. Interrogation of his ICD six months after placement demonstrated no recurrence of arrhythmia. Initially, he was treated with 40mg prednisone daily. After a three-month course he had continued active disease and was treated with infliximab. His treatment is ongoing; lab parameters are improving.
Cardiac sarcoidosis is rare. Conduction abnormalities are the most common finding, and arrhythmias are second. Heart failure, valvular dysfunction, and chronic effusion are also frequently observed, and one case report describes a large left atrial mass which behaved like a myxoma. This patient's case is unusual because of his large degree of sinus and cardiac involvement, as well as his unusual left ventricular cystic structure. Sarcoidosis should be considered in all patients who have unexplained structural heart disease, particularly young individuals. Treatment of cardiac sarcoidosis is aimed at controlling inflammation and preventing compromise of cardiac structure or function. Sources agree that steroids are an effective initial treatment, but the initial dose and optimal duration are unclear. This patient's course suggests that infliximab is an efficacious treatment option in severe cases.
PMCID: PMC4175938
4.  Multisystem Sarcoidosis in a Patient on Interferon-α Therapy for Chronic Hepatitis C 
Sarcoidosis is a chronic multisystemic granulomatous disease that is triggered by an autoimmune process. Nowadays, this pathology represents a well-recognized but uncommon complication for antiviral treatment in hepatitis C virus (HCV) infection. Herein, we report a remarkable case of 47-year-old woman treated for chronic HCV infection; the patient has developed interferon alfa-induced sarcoidosis involving the central nervous system. The evolution was fatal despite disrupting the antiviral therapy and initiating a high-dose corticotherapy. This complication of interferon alfa treatment was reported in the literature in only one case. Through this case and a review of the literature, we aim to underline the importance of screening for sarcoidosis before and during the follow-up of HCV patients undergoing antiviral therapy.
PMCID: PMC3385203  PMID: 22754249
Chronic hepatitis C; Complication; Interferon alfa; Neurosarcoidosis; Treatment
5.  Most Patients of Hepatitis C Virus Infection in India Present Late for Interferon-Based Antiviral Treatment: An Epidemiological Study of 777 Patients from a North Indian Tertiary Care Center 
Interferon-based antiviral therapy is offered only to those HCV patients who have either chronic hepatitis or early cirrhosis. Advanced cirrhotics do not tolerate interferon-based therapy. Since HCV is asymptomatic in early stages and usually presents late, the eligibility for interferon-based therapy is thus limited. There are scarce studies from India, which looked specifically the eligibility of interferon-based therapy in HCV patients.
To study the spectrum of presentation of HCV infection, determine their eligibility for interferon-based therapy, and follow for SVR.
The records of all consecutive patients of HCV, >14 years age, who presented to our department between 2008 and 2014, were analyzed for categorization into chronic hepatitis, cirrhosis and hepatocellular carcinoma. Patients with detectable HCV RNA who have chronic hepatitis or Child A cirrhosis were considered eligible for Peg-interferon and ribavirin. Patients who received treatment were followed for SVR.
777 patients (median age 49 [range 15–95] years, males 69%) were included. Cirrhosis was the most common presentation (56%, 439/777) followed by chronic hepatitis (37%, 287/777) and HCC (7%, 51/777). Of patients who had cirrhosis (including those with HCC), 36% (174/490) were Child A; 51% (250/490) were Child B and 14% (66/490) were Child C. Only 347/777 (45%) were eligible for Peg-interferon-alpha and Ribavirin. Among the remaining 430 patients, in 326 (76%) the disease was far too advanced. Of eligible patients only 54% actually received Peg-interferon-alpha and Ribavirin and 81% patients could complete the course. Of them only 70% could achieve SVR.
Most HCV patients in India present late and only about 45% are eligible for Interferon-based antiviral treatment. At presentation 56% patients already have cirrhosis and 7% have HCC. Since HCV is usually asymptomatic in early stages, awareness about screening should be increased so that more patients are diagnosed early before they develop cirrhosis or HCC.
PMCID: PMC4491643  PMID: 26155041
hepatitis C; cirrhosis; epidemiology; chronic liver disease; hepatocellular carcinoma; AFP, Alphafetoprotein; ALT, Alanine aminotransferase; ANA, Antinuclear antibody; BCLC, Barcelona Clinic Liver Cancer; DAA, Directly acting agents; FNAC, Fine needle aspiration cytology; HBV, Hepatitis B virus; HCC, Hepatocellular carcinoma; HCV, Hepatitis C virus; HIV, Human immunodeficiency virus; PCR, Polymerase chain reaction; PEG-IFN, Pegylated Interferon; RBV, Ribavirin; RNA, Ribonucleic acid; SMA, Smooth Muscle Antibody; SVR, Sustained virological response; WHO, World health organization
6.  Cutaneous Sarcoidosis: An Uncommon Side Effect of Pegylated Interferon and Ribavirin Use for Chronic Hepatitis C 
Case Reports in Gastroenterology  2009;3(3):366-371.
The treatment of chronic hepatitis C (CHC) has evolved in the past 15 years and combination of pegylated interferon plus ribavirin is its current standard therapy. However, several side effects are commonly observed and frequently lead to transient or definitive interruption of treatment. Although sarcoidosis in its systemic or cutaneous form is a very rare side effect in such circumstances, some cases have been reported even with conventional interferon. This brief review of the literature and description of a case of sarcoidosis occurring in a tattoo and a scar patient's face, during treatment with pegylated interferon alpha-2b plus ribavirin, is an educative report directed in special to dermatologists. The lesion improved after drug interruption and recurred after retreatment with pegylated interferon alpha-2a. We conclude that this side effect must call the attention of doctors to seek for the diagnosis and therapy as soon as possible in such circumstances. No differences were noticed neither with alpha-2a nor alpha-2b pegylated interferon employment.
PMCID: PMC2988931  PMID: 21103255
Sarcoidosis; Hepatitis C; Interferon; Pegylated interferon alpha; Granulomatous dermatitis; Tattoo
7.  Sarcoidosis and chronic hepatitis C: A case report 
Several case reports deal with the relationship between hepatitis C virus (HCV) infection and pulmonary or hepatic sarcoidosis. Most publications describe interferon α-induced sarcoidosis. However, HCV infection per se is also suggested to cause sarcoidosis. The present case report describes a case of biopsy-verified lung and liver sarcoidosis and HCV infection, and the outcome of antiviral therapy. In March 2009, a 25-year-old man presented with moderately elevated liver enzymes without any clinical symptoms. The patient was positive for HCV antibodies and HCV RNA of genotype 1b. Four months later the patient became dyspnoic and pulmonary sarcoidosis was diagnosed by lung biopsy and radiography. A short course of corticosteroid treatment relieved symptoms. Three months later, liver biopsy showed noncaseating granulomas consisting of epithelioid histiocytes and giant cells with a small amount of peripheral lymphocyte infiltration, without any signs of fibrosis. Chronic HCV infection with coexistence of pulmonary and hepatic sarcoidosis was diagnosed. Antiviral therapy with peginterferon α and ribavirin at standard doses was started, which lasted 48 wk, and sustained viral response was achieved. A second liver biopsy showed disappearance of granulomas and chest radiography revealed normalization of mediastinal and perihilar glands. The hypothesis that HCV infection per se may have triggered systemic sarcoidosis was proposed. Successful treatment of HCV infection led to continuous remission of pulmonary and hepatic sarcoidosis. Further studies are required to understand the relationship between systemic sarcoidosis and HCV infection.
PMCID: PMC3484354  PMID: 23155326
Pulmonary and hepatic sarcoidosis; Hepatitis C virus infection; Sustained viral response; Peginterferon α; Ribavirin
8.  Childhood sarcoidosis: A rare but fascinating disorder 
Childhood sarcoidosis is a rare multisystemic granulomatous disorder of unknown etiology. In the pediatric series reported from the southeastern United States, sarcoidosis had a higher incidence among African Americans. Most reported childhood cases have occurred in patients aged 13–15 years. Macrophages bearing an increased expression of major histocompatibility class (MHC) II molecules most likely initiate the inflammatory response of sarcoidosis by presenting an unidentified antigen to CD4+ Th (helper-inducer) lymphocytes. A persistent, poorly degradable antigen driven cell-mediated immune response leads to a cytokine cascade, to granuloma formation, and eventually to fibrosis. Frequently observed immunologic features include depression of cutaneous delayed-type hypersensitivity and a heightened helper T cell type 1 (Th1) immune response at sites of disease. Circulating immune complexes, along with signs of B cell hyperactivity, may also be found. The clinical presentation can vary greatly depending upon the organs involved and age of the patient. Two distinct forms of sarcoidosis exist in children. Older children usually present with a multisystem disease similar to the adult manifestations, with frequent hilar lymphadenopathy and pulmonary infiltrations. Early-onset sarcoidosis is a unique form of the disease characterized by the triad of rash, uveitis, and arthritis in children presenting before four years of age. The diagnosis of sarcoidosis is confirmed by demonstrating a typical noncaseating granuloma on a biopsy specimen. Other granulmatous diseases should be reasonably excluded. The current therapy of choice for sarcoidosis in children with multisystem involvement is oral corticosteroids. Methotrexate given orally in low doses has been effective, safe and steroid sparing in some patients. Alternative immunosuppressive agents, such as azathioprine, cyclophosphamide, chlorambucil, and cyclosporine, have been tried in adult cases of sarcoidosis with questionable efficacy. The high toxicity profile of these agents, including an increased risk of lymphoproliferative disorders and carcinomas, has limited their use to patients with severe disease refractory to other agents. Successful steroid sparing treatment with mycophenolate mofetil was described in an adolescent with renal-limited sarcoidosis complicated by renal failure. Novel treatment strategies for sarcoidosis have been developed including the use of TNF-alpha inhibitors, such as infliximab. The long-term course and prognosis is not well established in childhood sarcoidosis, but it appears to be poorer in early-onset disease.
PMCID: PMC2559831  PMID: 18811966
9.  Hypercalcemic crisis resulting from near drowning in an indoor public bath 
Male, 66
Final Diagnosis:
Hypercalcemic crisis
Near drowning state
Clinical Procedure:
Critical care medicine
Challenging differential diagnosis
Hypercalcemic crisis, generally caused by malignancy or primary hyperparathyroidism, is a life-threatening emergency that can result in multi-organ failure. Lowering the patient’s calcium level immediately and determining the correct etiology are essential.
Case Report:
We report a case of hypercalcemic crisis with a novel etiology. A 66-year-old male presented to the emergency room in cardiac arrest with a ventricular arrhythmia after being discovered submerged in an indoor public bath. He underwent cardioversion and was emergently intubated. Computed tomography showed bilateral pulmonary edema, suspected from water aspiration. Laboratory data revealed severe hypercalcemia and mild hypernatremia. Following three days of continuous hemodiafiltration, serum Ca decreased to and remained within normal limits. We concluded the etiology of hypercalcemia was absorption of Ca resulting from aspirated water.
Near drowning can be a cause of hypercalcemic crisis. For cases of near drowning, it is important to investigate the source of the aspirated water and consider electrolyte abnormalities in the diagnosis.
PMCID: PMC3700500  PMID: 23826470
hypercalcemia; near-drowning; emergency; hot springs
10.  Safety and efficacy of interferon-ribavirin combination therapy in HCV-HIV coinfected subjects: an early report 
Gut  2000;47(5):694-697.
BACKGROUND—More severe liver disease together with a poor response rate to α interferon argue for the use of more potent anti-hepatitis C virus (HCV) therapies in human immunodeficiency virus (HIV)-HCV coinfected patients, but the efficacy and safety of interferon-ribavirin combination therapy in HIV infected subjects are unknown.
AIM—To retrospectively evaluate the efficacy and safety of anti-HCV combination therapy in 21 HCV-HIV coinfected patients receiving antiretroviral therapy, and to access the clinical relevance of in vitro inhibition of phosphorylation by ribavirin of potent inhibitors of HIV—that is, zidovudine, stavudine, and zalcitabine.
PATIENTS—Twenty one patients were treated with combined antiretroviral therapy including zidovudine (n=8) or stavudine (n=13) (in association with protease inhibitors in 12). All received ribavirin (1000 or 1200 mg/day) and α interferon (3 MU three times/week) for chronic hepatitis C infection. All patients had not responded (n=20) or relapsed (n=1) after a previous six month course of α interferon therapy.
METHODS—HIV viral load (Monitor test) and CD4 cells count were measured at the beginning and every three months during and after ribavirin plus α interferon therapy over a mean period of 11 (1) months. Clinical and biological adverse effects were recorded.
RESULTS—There was no significant variation in HIV viral load or CD4 cell counts after three or six months of ribavirin therapy compared with baseline values. Of the 21 subjects, three (14%) had an increase in HIV viral load of more than 0.5 log leading to discontinuation of ribavirin in one. Eleven of 21 (52.4%) had initial negative HCV viraemia at three (n=10) or six (n=1) months but only six were polymerase chain reaction negative at the end of therapy, leading to rates for primary response and breakthrough of 23.8% and 28.5%, respectively. Six months after completion of therapy, three patients relapsed (14.3%) and three (14.3%) had sustained virological response. Median haemoglobin concentration decreased significantly after three and six months of ribavirin therapy (p= 0.0002 and p=0.0003, respectively) leading to withdrawal of therapy in one patient.
CONCLUSIONS—These preliminary results show that: (1) despite in vitro interactions between ribavirin, zidovudine, and stavudine, significant variation in HIV replication does not usually occur in HCV-HIV coinfected patients receiving ribavirin and different antiretroviral regimens, including zidovudine and stavudine; (2) α interferon and ribavirin combination therapy induced primary and sustained virological responses in 28.5% and 14.3% of treated subjects (who were previous non-responders to interferon therapy), respectively; (3) anaemia is a frequent adverse event. Such results should be confirmed in larger prospective trials.

Keywords: ribavirin; human immunodeficiency virus; hepatitis C virus; zidovudine; stavudine; antiretroviral therapy
PMCID: PMC1728127  PMID: 11034587
11.  Hepatitis C (chronic) 
BMJ Clinical Evidence  2010;2010:0921.
About 60% to 85% of people infected with hepatitis C virus will go on to develop chronic hepatitis C, which is now believed to affect 3% of the world's population.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions in treatment-naïve people with chronic hepatitis C infection, but without liver decompensation? What are the effects of interventions in people with chronic hepatitis C infection, but without liver decompensation, who have not responded to interferon treatment? What are the effects of interventions in people with chronic hepatitis C infection, but without liver decompensation, who relapse after interferon treatment? What are the effects of interventions in people with chronic hepatitis C infection who also have HIV? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 35 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: interferon monotherapy; interferon alfa plus ribavirin; peginterferon monotherapy; and peginterferon plus ribavirin.
Key Points
Chronic hepatitis C virus (HCV) infection is defined as persistent, detectable serum HCV RNA for a period greater than 6 months, with or without derangement in liver function tests. About 60% to 85% of people infected with HCV will go on to develop chronic hepatitis C, which is now believed to affect 3% of the world's population.Complications of chronic HCV infection include cirrhosis, compensated and decompensated liver disease, and hepatocellular carcinoma.Many people chronically infected with HCV remain asymptomatic, including a significant proportion of those who progress to cirrhosis, so routine screening of people in high-risk groups is advisable.
Interferon monotherapy produces a sustained virological response in both treatment-naïve people and people with cirrhosis or advanced fibrosis compared with placebo or no treatment. Interferon also improves liver histology, although it may not be effective in preventing hepatocellular carcinoma in people with cirrhosis.Efficacy is dependent on duration of treatment, with treatment for 12 months seeming more effective than treatment for 6 months. However, treatment for 12 months is associated with an increase in adverse effects.A dose of 6 MU of interferon three times weekly seems no more effective at achieving sustained virological response than 3 MU three times weekly, and is associated with an increased risk of adverse effects.
Adding ribavirin to interferon regimens further increases the likelihood of achieving sustained virological response, but also increases the risk of anaemia. Efficacy of combination therapy depends on genotype, with genotype 1-infected people typically requiring longer duration of treatment compared with genotype 2- and genotype 3-infected people.
Peginterferon monotherapy increases the proportion of treatment-naïve people who achieve sustained virological response compared with standard interferon monotherapy.
Adding ribavirin to peginterferon increases the likelihood of achieving sustained virological response compared with either peginterferon alone or standard interferon plus ribavirin. This is currently the standard recommended therapeutic approach.
In people previously non-responsive to interferon monotherapy, treatment with interferon alfa plus ribavirin increases the likelihood of achieving sustained virological response compared with interferon alone. This effect seems greater when the interferon dose is higher than 3 MU three times weekly, or the duration of the treatment is 12 months or greater.We don't know whether peginterferon as a monotherapy, or in combination with ribavirin, is effective in non-responders to interferon monotherapy. We don't know whether peginterferon plus ribavirin is more effective than interferon alfa plus ribavirin.
In people who relapse after interferon monotherapy, treatment with interferon plus ribavirin is more likely than interferon treatment alone to achieve sustained virological response (SVR). There is general consensus that peginterferon plus ribavirin is likely to improve the probability of achieving SVR in people who relapse after interferon monotherapy.We don't know whether peginterferon alone is effective at achieving SVR in people who relapse after interferon monotherapy.
In people co-infected with HCV and HIV, peginterferon plus ribavirin seems more effective than standard interferon plus ribavirin treatment or peginterferon alone at achieving SVR. Although interferon plus ribavirin seems less effective than peginterferon plus ribavirin, the proportion of people achieving SVR suggests that interferon plus ribavirin may be effective in people with HCV and HIV. We don't know whether interferon alone is effective in people co-infected with HCV and HIV.
PMCID: PMC2907607  PMID: 21718581
12.  Transient Visual Loss in a Hepatitis C Patient Treated With Pegylated Interferon Alfa-2a and Ribavirin 
Hepatitis Monthly  2014;14(2):e15124.
Patients with Hepatitis C are commonly treated with combination of Pegylated Interferon alfa-2a and Ribavirin. Less than 1% of patients receiving this treatment experience very uncommon ophthalmological side effects such as optic neuropathy and vision disorder, which are usually subclinical, mild and reversible, not requiring the withdrawal of the treatment. Retinopathy is the most commonly reported ocular side effect of interferon use, usually presenting with cotton wool spots and retinal hemorrhages.
Case Presentation:
We represent a case of severe retinopathy and optic neuropathy in a patient with chronic hepatitis C genotype 3a infection, treated with the combination of PEG-IFN alfa-2a (180 mkg once weekly) and Ribavirin (1200 mg daily). Bilateral visual loss of both eyes developed at 11th week of therapy and changes in retina and optic nerve were observed. Fluorescein angiography and optical coherence tomography showed bilateral anterior ischemic optic neuropathy and macular edema. Visual acuity improved 1 month and fundoscopic changes were no longer present 6 months after the urgent permanent discontinuation of PEG-IFN treatment and the pulse steroid therapy followed by a 2 week course of oral prednisone.
In case of interferon-associated retinopathy discontinuation of the therapy and treatment with high dose steroids can be beneficial. The prognosis of interferon-associated opthalmological side effects remains uncertain: in some patients visual acuity improves, other continues with poor visual outcome. Considering that, all patients should undergo ophthalmologic examination before treatment with interferon and their ophthalmological status should be monitored regularly while receiving this therapy.
PMCID: PMC3950629  PMID: 24693308
Hepatitis C, Chronic; Peginterferon alfa-2a; Optic Nerve Diseases; Pulse Therapy, Drug
13.  Acute pericarditis due to pegylated interferon alpha therapy for chronic HCV hepatitis - Case report 
BMC Gastroenterology  2011;11:30.
Cardio toxicity due to interferon therapy was reported only in small case series or case reports. The most frequent cardiac adverse effects related to interferon are arrhythmias and ischemic manifestations. The cardiomyopathy and pericarditis are rare but can be life threatening. The predisposing factors for interferon cardio toxicity were described only for ischemic manifestations and arrhythmias.
Case presentation
The authors report a case of pericarditis due to alpha interferon therapy for chronic hepatitis C, in a young woman without previous cardiac pathology. The clinical manifestations started during the 7-th month of interferon treatment. The cessation of interferon was necessary. After interferon discontinuation the patient recovered, with complete resolution of pericarditis. The patient scored 9 points on the Naranjo ADR probability scale, indicating a very probable association between pericarditis and interferon administration.
If a patient receiving interferon therapy complains of chest pain of sudden onset, a cardiac ultrasound should be performed in order to rule out pericarditis. We point out the possibility of an infrequent but severe adverse effect of interferon therapy.
PMCID: PMC3079687  PMID: 21453456
14.  Hepatic Sarcoidosis Mimicking Hilar Cholangiocarcinoma: Case Report and Review of the Literature 
Case Reports in Gastroenterology  2011;5(1):152-158.
Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. Hepatic involvement was reported in about 11% of patients with sarcoidosis. However, cases of sarcoidosis in which the granuloma is solitary and limited in the liver are very rare. A 51-year-old woman with tumors in the liver underwent extended left lobectomy with caudate lobectomy and bile duct resection. The tumor was located between segment 4 and the hilar region. Some daughter nodules were found in the left lobe, which were regarded as intrahepatic metastasis. Our case displayed clinical and radiologically distinct findings, which are very similar to those of hilar cholangiocarcinoma restricted to the liver. This report demonstrates that sarcoidosis can show solitary hepatic involvement in the absence of thoracic lymphadenopathy. In such a case, it is difficult to distinguish the diagnosis from other malignant neoplasms. In conclusion, the diagnosis of hepatic sarcoidosis has to be made through prudent and comprehensive investigations that include a full clinical history of sarcoidosis in other organs. Despite utilizing several detailed diagnostic modalities, the definitive diagnosis of cases of solitary sarcoidosis may remain difficult. In these cases, surgical treatment including liver resection should be considered in order to avoid missing a suitable opportunity for treatment.
PMCID: PMC3088740  PMID: 21552437
Sarcoidosis; Hepatic sarcoidosis; Hepatic granulomas; Hilar cholangiocarcinoma
15.  Pulmonary sarcoidosis associated with psoriasis vulgaris: coincidental occurrence or causal association? Case report 
Sarcoidosis is rarely associated with a distinct disease. One disease infrequently associated with sarcoidosis is psoriasis.
Case presentation
This case study describes a 38-year-old male, who presented with chest pain, high-grade fever, arthralgias and a skin rash accompanied by bilateral hilar lymphadenopathy on his chest radiograph. Extensive investigations including fiber-optic bronchoscopy with bronchoalveolar lavage and labial and skin biopsies, demonstrated that two distinct clinical entities co-existed in the same patient: pulmonary sarcoidosis and psoriasis vulgaris. Combination therapy for both diseases was applied and the patient was greatly improved.
This is the first well-documented case of sarcoidosis and psoriasis in the same patient, reported on the basis of safe and widely-used techniques that were not available until fairly recently. These disorders might share common pathogenic mechanisms that could explain their co-existence in the patient.
PMCID: PMC1716762  PMID: 17166281
16.  FDG-PET/CT of sarcoidosis and sarcoid reactions following antineoplastic treatment 
SpringerPlus  2013;2:113.
Sarcoidosis or sarcoid reactions, which appear as FDG-avid lesions in oncologic patients, need to be differentiated from disseminated malignancies. We aimed to promote awareness of development of sarcoidosis or sarcoid reactions after antineoplastic therapy to avoid diagnostic errors with FDG-PET/CT findings and assess the utility of FDG-PET/CT for follow-up. We retrospectively reviewed radiological reports of FDG-PET/CT scans performed between January 2009 and December 2011. Among oncologic patients with more than 2 FDG-PET/CT scans, those with nearly symmetrical increases in FDG uptake in the hilar or mediastinal lymph nodes were identified, and those with known sarcoidosis, concurrent diagnoses of sarcoidosis with malignancy, or histopathologically proven malignancies were excluded. Then, only those cases were selected for which sarcoidosis or sarcoid reactions were diagnosed. Four of 376 oncologic cases met the criteria. At 9 months to 6 years after antineoplastic therapy, abnormal FDG uptakes were observed in the hilar, mediastinal, abdominal, pelvic, and inguinal nodes, and/or spleen and lung parenchyma with SUVmax up to 17.7. On the basis of these findings, 1 patient received anticancer chemotherapy because of tumor recurrence suspicion. A gradual decrease in FDG uptake was observed on subsequent PET/CT scans. Sarcoidosis or sarcoid reactions should be considered in differential diagnosis of oncologic patients who have developed FDG-avid lesions any time after antineoplastic therapy. FDG-PET/CT can be used for follow-up in nondiagnostic situations to detect decreases in FDG uptake due to presence of sarcoidal granulomas.
PMCID: PMC3610027  PMID: 23543853
FDG; PET; Sarcoid reactions; Sarcoidosis; Malignancy; Cancer; Lymphadenopathy
17.  Cutaneous and pulmonary sarcoidosis following treatment of multiple sclerosis with interferon-β-1b: a case report 
Several cases of sarcoidosis following treatment with interferon-α have been reported in the literature, but those following interferon-β are very rare. We report the case of a patient with multiple sclerosis who developed pulmonary and cutaneous sarcoidosis following treatment with Betaseron® (interferon-β-1b).
Case presentation
A 33-year-old Caucasian woman with a history of multiple sclerosis, treated with interferon-β-1b for 2.5 years developed erythema nodosum in her lower limbs, a breast abscess, and unilateral adenopathy of her left lung. A skin biopsy confirmed sarcoidosis. After the discontinuation of interferon-β-1b and treatment with indomethacin and prednisolone, she recovered.
Sarcoidosis is considered one of the most common multiple sclerosis imitators with involvement of the central nervous system. However, although rare, sarcoidosis can develop following treatment with interferon-β-1b and should be considered in patients with multiple sclerosis treated with beta-interferons who develop pulmonary or extra-pulmonary manifestations of sarcoidosis. Interferon-β-1b discontinuation is the first and most important step in the treatment of such cases followed by treatment with corticosteroids.
PMCID: PMC3917520  PMID: 24330713
Interferon-β; Multiple sclerosis; Sarcoidosis
18.  Ischemic colitis during interferon-ribavirin therapy for chronic hepatitis C: A case report 
Ischemic colitis is a rare complication of interferon administration. Only 9 cases in 6 reports have been described to-date. This report describes a case of ischemic colitis during pegylated interferon and ribavirin treatment for chronic hepatitis C, and includes a review of the relevant literature. A 48-year-old woman was treated with pegylated interferon α-2a and ribavirin for chronic hepatitis C, genotype Ib. After 19 wk of treatment, the patient complained of severe afebrile abdominal pain with hematochezia. Vital signs were stable and serum white blood cell count was within the normal range. Abdominal computed tomography showed diffuse colonic wall thickening from the splenic flexure to the proximal sigmoid colon, which is the most vulnerable area for the development of ischemic colitis. Colonoscopy revealed an acute mucosal hyperemic change, with edema and ulcerations extending from the proximal descending colon to the sigmoid colon. Colonic mucosal biopsy revealed acute exudative colitis. Polymerase chain reaction and culture for Mycobacterium tuberculosis were negative and the cultures for cytomegalovirus, Salmonella and Shigella species were negative. After discontinuation of interferon and ribavirin therapy, abdominal pain and hematochezia subsided and, following colonoscopy showed improvement of the mucosal ulcerations. Ischemic colitis cases during interferon therapy in patients with chronic hepatitis C reported so far have all involved the descending colon. Ischemic colitis is a rarely encountered complication of interferon administration in patients with chronic hepatitis C and should be considered when a patient complains of abdominal pain and hematochezia.
PMCID: PMC3422808  PMID: 22919260
Ischemia; Hepatitis C; Interferon
19.  Severe hypercalcemia unmasked by Vitamin D in a patient with sarcoidosis 
Indian Journal of Nephrology  2013;23(5):375-377.
Severe hypercalcemia is uncommon in clinical practice and is usually due to primary hperparathyroidism or malignancy. We present a patient who presented with severe hypercalcemia with renal failure; further evaluation of which revealed the diagnosis of sarcoidosis. This case is presented in view of the rarity of presentation of sarcoidosis with hypercalcemic crisis.
PMCID: PMC3764716  PMID: 24049278
Hypercalcemia; renal failure; sarcoidosis; Vitamin D
20.  Sarcoidosis with major airway, vascular and nerve compromise 
The present report describes a 60-year-old Caucasian woman who presented with progressive dyspnea, cough and wheeze. A computed tomography scan of the chest showed innumerable bilateral inflammatory pulmonary nodules with bronchovascular distribution and a mediastinal and hilar infiltrative process with calcified lymphadenopathy leading to narrowing of lobar bronchi and pulmonary arteries. An echocardiogram revealed pulmonary hypertension. Bronchoscopy showed left vocal cord paralysis and significant narrowing of the bilateral bronchi with mucosal thickening and multiple nodules. Transbronchial biopsy was compatible with sarcoidosis. Despite balloon angioplasty of the left lower lobe and pulmonary artery, and medical therapy with oral corticosteroids, her symptoms did not significantly improve. To the authors’ knowledge, the present report describes the first case of pulmonary sarcoidosis resulting in major airway, vascular and nerve compromise due to compressive lymphadenopathy and suspected concurrent granulomatous infiltration. Its presentation mimicked idiopathic mediastinal fibrosis.
PMCID: PMC3956332  PMID: 23717817
Airway narrowing; Mediastinal fibrosis; Pulmonary hypertension; Sarcoidosis; Vocal cord paralysis
21.  Neuro-ophthalmic sarcoidosis. 
Sarcoidosis is a multisystem disorder in which ocular involvement occurs in about one-quarter and neurosarcoidosis in 7 per cent of patients. When the retina is involved, the reported incidence of central nervous system sarcoidosis is 37 per cent. The patient described had a transient papular eruption of the legs, bilateral hilar lymphadenopathy, polyarthralgia with knee effusions, and bilateral facial and peripheral neuropathy. Ocular involvement was characterized by anterior uveitis (in the initial stages), vitreous flare, bilateral disc oedema, macular oedema, streak haemorrhages, peripheral periphlebitis, nerve fibre bundle defects, and candle-wax spots. Fluorescein angiography showed no fluorescence of the candle-wax spots nor of the adjacent vessels. However, there was hyperfluorescence of two retinal lesions. This patient had unilateral internal ophthalmoplegia, only three cases of which have been reported in the literature. Her health was restored by heavy, prolonged corticosteroid therapy. Her family history revealed that an uncle died of sarcoidosis complicated by cryptococcal meningitis. The literature on retinopathy in sarcoidosis is reviewed and the lesions noted in the posterior segment are listed.
PMCID: PMC1017428  PMID: 1203222
22.  Interferon-induced sarcoidosis 
BMJ Case Reports  2011;2011:bcr0320113929.
Sarcoidosis is a rare side effect of interferon therapy that has been reported over the last years. We present the case of a 43-year-old man presenting with systemic sarcoidosis during treatment with pegylated interferon and ribavirin. Skin lesions, which were found to be associated with asymptomatic bilateral hilar lymph nodes and pulmonary nodules, were the sole clinical manifestation of the disease. Stopping therapy resulted in clinical and radiological improvement.
PMCID: PMC3082057  PMID: 22696628
23.  Multiple Sclerosis Like Condition in a Patient of Hepatitis C after Treatment with Interferon Alpha: A Case Report 
Hepatitis C virus affects millions of people around the world. The primary therapy comprises of interferon alpha and ribavarin. The most common side effects of this treatment include flu like symptoms and psychiatric issues. One of the rare complications of the combined therapy is the development of demyelinating lesions in the central nervous system. Our case report presents a 35-year-old man who was a known case of Hepatitis C presenting to us with altered level of consciousness and decreased vision. He had been treated as per the standard therapy for Hepatitis C infection with interferon alpha and ribavarin. During the course of this therapy, he developed significant loss of vision. This was in fact due to serious and rare complication of the treatment which was demonstrated on the MRI as demyelinating lesions in the deep periventricular white matter bilaterally. Visual Evoked Potential study was performed which concluded bilateral dysfunction of the optic pathway. The treatment of Hepatitis C with interferon alpha and ribavarin may present with a wide array of adverse effects which includes a rare complication of central nervous system demyelination as well. Research suggests that early treatment of Multiple Sclerosis (MS) is beneficial in the long run with a better prognosis and minimal changes on MRI of the patient. Therefore this complication of the treatment should be kept in mind as one of the main differential diagnosis. By finding the extent of the inflammation, and consequently doing an MRI alongside a lumbar puncture, can serve to diagnose a rare condition mimicking multiple sclerosis while treating with interferon alpha.
PMCID: PMC4484105  PMID: 26155513
MRI; Optic neuritis; White and gray matter
24.  Hypercalcemic crisis due to adult T cell leukemia: a rare cause of paralytic ileus 
Annals of Gastroenterology  2012;25(2):170-172.
Adult T cell leukemia- lymphoma is a rare aggressive malignancy of the peripheral T lymphocytes, caused by human T cell lymphotropic virus -1 (HTLV-1) infection. Hypercalcemia occurs in about 70% of patients with acute adult T cell leukemia. However, there are very few case reports of adult T cell leukemia presenting as a hypercalcemic crisis. We report a case of a 54-year-old male who presented with abdominal pain, constipation and altered sensorium. On examination he had generalized lymphadenopathy, hepatosplenomegaly and paralytic ileus. Investigation revealed hypercalcemic crisis with low parathormone (PTH) levels. Peripheral smear and bone marrow aspirate were consistent with adult T cell leukemia. HTLV-1 serology was positive. Despite the corrective measures for hypercalcemia and chemotherapy, he succumbed to the illness in a week.
PMCID: PMC3959384  PMID: 24714244
paralytic ileus; hypercalcemic crisis; adult T cell leukemia; human T cell lymphotropic virus (HTLV) -1
25.  Clinical impact of treatment timing for chronic hepatitis C infection: a decision model 
Journal of Viral Hepatitis  2015;22(8):630-638.
Recent advances in the treatment of hepatitis C virus (HCV) infection have led to the availability of both highly efficacious interferon-containing and interferon-sparing regimens. However, the use of such therapies faces restrictions due to high costs. For patients who are medically eligible to receive interferon, the choice between the two will likely be impacted by preferences surrounding interferon, severity of disease, coverage policies and out-of-pocket costs. We developed a decision model to quantify the trade-offs between immediate, interferon-containing therapy and delayed, interferon-free therapy for patients with chronic, genotype 1 HCV infection. We projected the quality-adjusted life expectancy stratified by the presence or absence of cirrhosis for four strategies: (i) no treatment; (ii) immediate, one-time treatment with an interferon-containing regimen; (iii) immediate treatment as above with the opportunity for retreatment in patients who fail to achieve sustained virologic response with interferon-free therapy in 1 year; and (iv) delayed therapy with interferon-free therapy in 1 year. When compared to one-time immediate treatment with the interferon-containing regimen, delayed treatment with the interferon-free regimen in 1 year resulted in longer life expectancy, with a 0.2 quality-adjusted life year (QALY) increase in noncirrhotic patients, and a 1.1 QALY increase in patients with cirrhosis. This superiority in health benefits was lost when wait time for interferon-free therapy was greater than 3–3.2 years. In this modelling analysis, interferon-free therapy resulted in superior health benefits compared to immediate therapy with interferon until wait time exceeded 3–3.2 years. Such data can inform decision-making regarding treatment initiation for HCV as healthcare financing evolves.
PMCID: PMC4515086  PMID: 26135026
decision analysis; HCV; interferon sparing; treatment timing

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