Hodgkin's lymphoma accounts for ten percent of all lymphomas. In the United States, there are about 8000 new cases every year. This paper describes a case of lymphocyte-rich Hodgkin's lymphoma (LRHL) manifested by autoimmune hemolytic anemia (AIHA). A 27-year-old Israeli male presented with dizziness associated with one month of low-grade fevers and night sweats; he also complained of persistent cough, pruritus, and ten-pound weight lost during this time. The CBC revealed hemoglobin of 5.9 gm/dL, and direct Coomb's test detected multiple nonspecific antibodies consistent with the diagnosis of AIHA. Chest, abdomen, and pelvic CT scan showed mediastinal lymphadenopathy and splenomegaly. Lymph node biopsy revealed classic LRHL. AIHA resolved after completion of the first cycle of chemotherapy with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD); after six cycles, he went into complete remission. Although infrequent, AIHA can be responsible for the presenting symptoms of HL.
Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disorder defined by the combination of biochemical abnormalities, tubulointerstitial nephritis, and uveitis. We describe a 12-year-old female, presented with a ten-day history of fever, characterized by sudden onset and rapid spontaneous resolution in few hours, accompanied by shivering, extreme fatigue, and loss of appetite. Laboratory values were consistent with renal failure of tubular origin. Renal biopsy confirmed a tubulointerstitial nephritis, with acute tubulitis, polymorphonuclear infiltration, and microabscesses. The renal interstitium was occupied by a dense inflammatory infiltrate, consisting of lymphocytes, plasma cells, and neutrophils. Glomerular structures were preserved. Ophthalmological examination that suggested a previous asymptomatic bilateral uveitis and HLA typing (HLA-DQA1∗0101/0201 and HLA-DQB1∗0303/0503) further supported the suspect of TINU syndrome. TINU syndrome is probably an underdiagnosed disorder, responsible for many cases of idiopathic anterior uveitis in young patients, especially in those who have asymptomatic renal disease and when proper diagnostic tests are not performed at the time of presentation.
Patients with systemic lupus erythematosus (SLE) have an increased risk of acute myocardial infarction (AMI). We examined if nephritis or other clinical manifestations of SLE identified patients at increased risk.
In this population-based case-control study, we identified patients with SLE hospitalized with an AMI in California in 1996–2000. We compared the frequency of six manifestations of SLE (nephritis, pleuritis, hemolytic anemia, thrombocytopenia, psychosis/major depression, seizures) and of venous thrombosis/pulmonary embolism, in this group (n=535) to the frequency of these manifestations in two control groups: patients with SLE hospitalised for pulmonary disease (n=529), and patients with SLE hospitalised for gastrointestinal bleeding (n=349).
Nephritis was present in 23.7% of patients with AMI, 11.0% of patients with pulmonary disease and 25.2% of patients with gastrointestinal bleeding. In adjusted analyses, nephritis was more common in the AMI group (odds ratio (OR) 2.85, 95% confidence interval (CI) 1.97–4.14; p<.0001) than in the pulmonary disease control group. Among women, nephritis was more common in the AMI group (OR 2.83; 95% CI 1.33–6.01; p=0.007) than in the gastrointestinal bleeding control group. Psychosis/major depression was less common among patients with AMI.
Among patients with SLE, nephritis was associated with 2.8-fold increased risk of AMI.
Systemic lupus erythematosus; myocardial infarction; cardiovascular disease; lupus nephritis
Fever with generalised lymphadenopathy is a common presentation in clinical practice. A degree of lymphadenopathy is frequently a characteristic of established systemic lupus erythematosus (SLE), but it is rarely the primary presenting feature. A 25-year-old man presented with night sweats, weight loss and generalised lymphadenopathy. A chest computed tomography scan confirmed the presence of mediastinal, hilar and axillary lymphadenopathy, with bilateral pleural effusions. The double stranded DNA antibody (anti-dsDNA) was absent. Subsequently, there was mild renal impairment and a renal biopsy showed lupus nephritis. Anti-dsDNA was positive using an alternative assay. Treatment with prednisolone and mycophenolate mofetil led to considerable clinical improvement. Extensive lymphadenopathy as the first clinical manifestation of SLE is rare and this case also illustrates the variable results obtained from different anti-dsDNA antibody assays.
Hepatitis A virus (HAV) infection is generally a self-limited disease, but the infection in adults can be serious, to be often complicated by acute kidney injury (AKI) and rarely by virus-associated hemophagocytic syndrome (VAHS). Our patient, a 48-yr-old man, was diagnosed with HAV infection complicated by dialysis-dependent AKI. His kidney biopsy showed acute tubulointerstitial nephritis with massive infiltration of activated macrophages and T cells, and he progressively demonstrated features of VAHS. With hemodialysis and steroid treatment, he was successfully recovered.
Acute Hepatitis A; Acute Kidney Injury; Lymphohistiocytosis, Hemophagocytic
Coombs' negative autoimmune hemolytic anemia (AIHA) is a rare disease which shares similar clinical and hematological features with Coombs' positive AIHA, but its exact frequency remains unknown. There have been few reports of idiopathic thrombocytopenic purpura (ITP) and Coombs' negative AIHA associated with other lymphoproliferative disorders (LPDs). Since there is a well known association between LPDs and autoimmune phenomena, it is important to investigate the possibility of an underlying malignancy. We report a case of ITP and Coombs' negative AIHA associated with diffuse large B-cell lymphoma.
Lymphoma; Hemolytic anemia; Coombs' test; Idiopathic thrombocytopenic purpura
Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease entity usually occurring in children. In the present study a case of TINU syndrome in an elderly patient is described and relevant literature is reviewed. A 61-year-old man presented with bilateral flank pain, urinary frequency, and foamy urine. A kidney ultrasonography revealed an increase in kidney parenchyma echogenicity. Following a kidney biopsy, the patient was diagnosed with acute tubulointerstitial nephritis. An ophthalmology examination initially performed for floater symptoms, revealed anterior uveitis in both eyes. Acute tubulointerstitial nephritis and anterior uveitis in both eyes responded to treatment with oral prednisolone, furosemide, carvedilol, and a topical steroid. TINU syndrome can occur in the elderly and should be part of the differential diagnosis when seeing a patient who has uveitis in association with renal disease; any therapy should be managed by both an internist and an ophthalmologist.
Interstitial nephritis; Nephritis; Renal diseases; Tubulointerstitial nephritis and uveitis; Uveitis
Giant cell hepatitis (GCH) with autoimmune hemolytic anemia is a rare entity, limited to young children, with an unknown pathogenesis. We report the case of 9-mo old who presented with fever, diarrhea and jaundice four days before hospitalization. Physical examination found pallor, jaundice and hepatosplenomegaly. The laboratory workup showed serum total bilirubin at 101 μmol/L, conjugated bilirubin at 84 μmol/L, hemolytic anemia, thrombocytopenia and immunoglobulin G (IgG) and anti-C3d positive direct Coombs’ test. The antinuclear, anti-smooth muscle and liver kidney microsomes 1 non-organ specific autoantibodies, antiendomisium antibodies were negative. Serological assays for viral hepatitis B and C, cytomegalovirus, herpes simplex and Epstein Barr virus were negative. The association of acute liver failure, Evan’s syndrome, positive direct Coomb’s test of mixed type (IgG and C3) and the absence of organ and non-organ specific autoantibodies suggested the diagnosis of GCH. The diagnosis was confirmed by a needle liver biopsy. The patient was treated by corticosteroids, immunomodulatory therapy and azathioprine but died with septicemia.
Giant cell hepatitis; Anemia; Hemolytic; Autoimmune; Child
Autoimmune Hemolytic Anemia (AIHA), a very infrequent condition which represents a group of disorders in which presence of autoantibodies directed against self-antigens leads to shortened red cell survival. Till date, a very few cases of AIHA in Malaria patients are reported worldwide but still AIHA should be considered a relatively rare cause of anemia in malaria. A 20 year male presented with intermittent fever since seven days and yellowish discoloration of urine and sclera since 5 days. He was transfused three units of blood at a private clinic before one month. On examination, pallor, icterus and spelnomegaly were present. Hemoglobin (Hb) was 3.2 gm% and peripheral smear revealed ring forms of both Plasmodium vivax and Plasmodium falciparum. Serum LDH and Serum billirubin (Indirect and Direct) were high. This patient’s blood group was B +ve with positive autocontrol. Indirect Antiglobulin Test (IAT), antibody screening and antibody identification were pan-positive with reaction strength of +4 against each cell. Direct Antiglobulin Test was +4 positive anti IgG and negative with anti C3. He was treated with Artesunate and methylprednisone. Least incompatible, saline washed O Neg and B neg red cells were transfused on the 2nd day of starting treatment. Hb was raised to 6.1 gm% on 4th day. Patient was discharged on 9th day with Hb 7.0 gm% with oral tapering dose of steroids. In the above case, patient was suffering from high grade malarial parasitemia with co-existing autoimmune RBC destruction by IgG auto-antibodies which led to sudden drop in Hb and rise in serum LDH and indirect billirubin. Least incompatible packed red cells along with antimalarials and steroids led to clinical improvement. So far, one case report each from India, Korea, Canada and Germany and one case series report of three cases from India have been reported. Under-reporting or rarity of this phenomenon may be accountable for this.
Autoimmune Hemolytic Anemia; autoantibodies; malaria
Graves' disease (GD) is associated with various hematologic abnormalities but pancytopenia and autoimmune hemolytic anemia (AIHA) are reported very rarely. Herein, we report a patient with GD who had both of these rare complications at different time intervals, along with a review of the related literature. The patient was a 70-year-old man who, during a hospitalization, was also noted to have pancytopenia and elevated thyroid hormone levels. Complete hematologic workup was unremarkable and his pancytopenia was attributed to hyperthyroidism. He was started on methimazole but unfortunately did not return for followup and stopped methimazole after a few weeks. A year later, he presented with fatigue and weight loss. Labs showed hyperthyroidism and isolated anemia (hemoglobin 7 g/dL). He had positive direct Coombs test and elevated reticulocyte index. He was diagnosed with AIHA and started on glucocorticoids. GD was confirmed with elevated levels of thyroid stimulating immunoglobulins and thyroid uptake and scan. He was treated with methimazole and radioactive iodine ablation. His hemoglobin improved to 10.7 g/dL at discharge without blood transfusion. Graves' disease should be considered in the differential diagnosis of hematologic abnormalities. These abnormalities in the setting of GD generally respond well to antithyroid treatment.
Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare autoimmune disease and the pathogenesis is still unknown. We report a case of TINU syndrome with high ASLO titer.
Uveitis improved and urine β2-MG normalized with low dose systemic predonisolone and cyclosporin A. The high ASLO titer in early phase suggested that streptococcal infection might have triggered TINU syndrome. Lymphocyte phenotypes normalized after treatment with low dose systemic predonisolone and cyclosporin A.
TINU syndrome; ASLO titer; Lymphocyte phenotype
Clinical manifestations of Q fever infection are fever, productive cough, decrease in exercise tolerance and chills. Cardiovascular involvement is well recognized and usually presents as endocarditis and infection of an aneurysm or vascular graft. Myocarditis has only rarely been described as a manifestation of acute Q fever infection. In this report we describe a case of a young adult who presented with angina-like symptoms and ECG and biochemical markers indicative of acute coronary syndrome. The diagnosis of myocarditis was ultimately made based on the results of a normal coronary angiography and increased anti-Coxiella burnetii antibody titer. The patient has not developed dilated cardiomyopathy after two years of follow up.
Coxiella burnetii; Q fever; myocarditis; antibody titer
Cytomegalovirus is a common virus responsible for a wide range of clinical manifestations. Hemolysis is a rare but potentially life-threatening complication of cytomegalovirus infection, described mostly in immunocompromised patients, the pathogenesis of which is still unclear.
We performed a review of the literature regarding cases of hemolytic anemia during acute cytomegalovirus infection in apparently immunocompetent individuals. We searched for relevant articles in PubMed for the period of 1980 through 2008.
We describe a case of Coombs-negative hemolytic anemia in a 44-year-old Caucasian immunocompetent man with acute cytomegalovirus infection.
Clinicians should consider cytomegalovirus infection in the differential diagnosis of hemolytic anemia in immunocompetent adults. Possible therapeutic options include antiviral therapy and steroids, although the best treatment strategy is still controversial.
Wilson’s disease is a rare inherited disorder of copper metabolism causing severe damage to vital organs. Liver and brain disorders are the main manifestations. Severe hemolytic anemia is an unusual complication of Wilson’s disease. We present a case who developed spherocytic acute hemolytic anemia (Coomb’s negative) as the initial manifestation of Wilson’s disease. On examination Kayser- Fleischer ring was found. Laboratory data supported a diagnosis of Wilson’s disease.
Wilson’s disease (WD); Spherocytic anemia
The capacity for herpesvirus to cause disease in cetaceans is unclear and may be varied depending on the different conditions of individuals and between different species. Kidney pathology and intralesional virus-associated infection have been rarely reported in cetaceans.
On April 2004, an old adult male Blainville’s beaked whale (Mesoplodon densirostris) 420 cm long with a poor body condition was stranded on Tenerife Island. During necropsy, no gross lesions were observed in the kidneys. However, membranous glomerulonephritis, multifocal interstitial lymphoplasmacytic nephritis and acute multifocal necrotizing tubulointerstitial nephritis with intranuclear inclusion bodies was diagnosed by histological analysis. Tissue samples were submitted for bacteriological analysis and molecular viral screening.
A novel alpha herpesvirus associated with interstitial nephritis was identified in an old adult male Blainville's beaked whale (M. densirostris) with a poor body condition stranded in the Canary Islands. This report suggests that identification of herpesvirus infection could be used as a differential diagnosis for interstitial nephritis in cetaceans.
Beaked whale; Interstitial nephritis; Alpha herpes virus; Diagnosis
Systemic lupus erythematosus (SLE) is a prototype autoimmune disease that affects multiorgan systems. Lupus nephritis is one of the most severe manifestations of SLE whereby immune-mediated inflammation can lead to permanent damage within the glomerular, tubulo-interstitial, and vascular compartments of the kidney, resulting in acute or chronic renal failure. The mechanisms that regulate host inflammatory responses and tissue injury are incompletely understood. Accumulating evidence suggests that hyaluronan and its interaction with its cell surface receptor CD44 plays an important role in mediating pathogenic mechanisms in SLE. This paper discusses the putative mechanisms through which hyaluronan and CD44 contribute to the pathogenesis of SLE, with particular emphasis on lupus nephritis.
We report a rare case of dengue fever triggering systemic lupus erythematosus and lupus nephritis. The patient presented herself during a large outbreak of dengue fever in December 2012 in Maharashtra, India. The diagnosis of dengue fever was confirmed by the presence of NS-1 antigen during the first few days of febrile illness. Eight weeks later, kidney tissue biopsy studies revealed evidence of lupus nephritis on microscopic examination and immunofluorescence. The report interpreted it as focal proliferative glomerulonephritis and segmental sclerosis (Stage IIIC). The case was also found positive for perinuclear antineutrophil cytoplasmic antibodies by indirect immunofluorescence assay. An active and effective management of a case essentially calls for clear perception of differentiating dengue-induced lupus flare, antineutrophil cytoplasmic antibody-related nephropathy, and/or dengue-induced de-novo lupus disease. Dengue viremia may be the trigger for immune complex formation in patients who are predisposed to developing autoimmune diseases. The present case explains the importance of considering the diagnosis of dengue-related lupus nephritis as an atypical occurrence in appropriate situations, as in this case. It would not be improper to regard this escalating disease as an expanded feature of dengue.
kidney biopsy; glomerulonephritis; segmental sclerosis; lupus flare; dengue viremia; autoimmune; de-novo lupus nephritis
Between January 1979 and June 1985, 10 patients with acute allergic interstitial nephritis were seen in a clinical nephrology service at a large regional hospital. The onset of renal failure was temporally related to the use of a drug: a nonsteroidal anti-inflammatory agent (NSAID) (in four patients), cimetidine (in three), antibiotics (in two) or allopurinol (in one). The onset of renal failure was acute in three patients and insidious in seven. Two patients also exhibited marked proteinuria. Clinical features such as fever, rash, hematuria, pyuria with or without eosinophiluria, and mild to marked proteinuria had led to suspicion of the disease. The diagnosis was confirmed by renal biopsy findings of inflammatory cells, predominantly lymphocytes, plasma cells and eosinophils. Three patients required hemodialysis; two of them received steroids as well. Steroid therapy was also used in two patients with NSAID-induced proteinuria. Renal function improved in nine patients by 35 days, but one patient continued to have slow but progressive deterioration of renal function. Acute interstitial nephritis can be distinguished from other forms of acute renal failure by heavy renal uptake of gallium 67, maximal 48 hours or more after injection. The improvement in renal function after discontinuation of the implicated drug, the characteristic histopathological findings of allergic interstitial nephritis, and the presence of eosinophils and sometimes IgE in the blood suggest a hypersensitivity reaction.
Celiac disease (CD) is a common autoimmune condition. Previously it was considered to be a rare childhood disorder, but is actually considered a relatively common condition, present at any age, which may have multiple complications and manifestations. Hematological disorders of the disease are not uncommon. Among these disorders, the most frequently reported are anemias as a result of iron deficiency, often associated with folate and/or B12 deficiency. Anemias caused by hemolysis are very rarely reported in celiac patients. An 11-year-old girl with a previous uneventful medical history presented with severe hemolytic anemia. Hemolysis was Coombs negative, accompanied by inappropriate low reticulocyte count, despite exaggerated bone marrow hyperplasia of the erythroid precursors which showed normal maturation. Serology for recent infections, including Epstein-Barr virus, parvovirus B19, cytomegalovirus and mycoplasma, were all negative. Levels of serum IgA, IgG and IgM, were all within normal ranges for age. Screening for anti-DNA, antinuclear, antineutrophil cytoplasmic, antimicrosomal, antithyroglobulin, and antimitochondrial antibodies and lupus anticoagulants, was negative. She was also negative for human immunodeficiency virus. Conventional therapy with corticosteroids and intravenous immunoglobulin failed. CD was serendipitously discovered upon screening for anti-tissue transglutaminase autoantibodies. The disease was confirmed by biopsy of the small intestine mucosa. The patient recovered with gluten-free diet. A unique case of CD is presented. CD should be serologically screened in each patient with Coombs negative “immune” hemolytic anemia, particularly if accompanied by “reticulocytopenia”. A new hemolytic mechanism and very speculative explanation for “reticulocytopenia” are discussed.
Celiac disease; Tissue transglutaminase; Antibodies; Hemolytic anemia; Gluten free diet
Acute interstitial nephritis (AIN) is an important cause of reversible acute kidney injury. At least 70% of AIN is caused by various drugs, mainly penicillines and non-steroidal anti-inflammatory drugs. Quinolones are only rarely known to cause AIN and so far cases have been mainly described with older fluoroquinolones.
Here we describe a case of biopsy proven interstitial nephritis after moxifloxacin treatment. The patient presented with fever, rigors and dialysis dependent acute kidney injury, just a few days after treatment of a respiratory tract infection with moxifloxacin. The renal biopsy revealed dense infiltrates mainly composed of eosinophils and severe interstitial edema. A course of oral prednisolone (1 mg/kg/day) was commenced and rapidly tapered to zero within three weeks. The renal function improved, and the patient was discharged with a creatinine of 107 μmol/l.
This case illustrates that pharmacovigilance is important to early detect rare side effects, such as AIN, even in drugs with a favourable risk/benefit ratio such as moxifloxacin.
Immune dysregulation is the hallmark of all autoimmune
diseases. It is extremely interesting to study the associations
and pathogenesis of the various autoimmune diseases, like
the link between the AIHA and CLL. This link is well
established and is based on the fact that there is loss of
tolerance to the self-antigen, which in turn leads to immunebased
hemolytic anemia. Around 30% of the patients
with CLL are at the risk of developing AIHA, and 11%
eventually develop AIHA. Whether there is any definite
linkup between the corrupted immune system and “acute”
leukemias/lymphomas is yet to be established. Needless to
say, if there was an association between the pathogenesis of
the ALLs and AIHA, it would be a landmark in the field of
oncology as it would enforce early diagnosis and treatment
for the disease which is much more aggressive and found
in a comparatively younger age group (predominantly in
children and a mean age of 40 years in adults) as compared
to its chronic counterparts.
The AIHA would serve as a “tip to the underlying
iceberg” in these situations, warning us of the cryptic
Pericarditis is a rare manifestation of tuberculosis (Tb) in children. A 14-yr-old Korean boy presented with cardiac tamponade during treatment of pulmonary tuberculosis. He developed worsening anemia and persistent fever in spite of anti-tuberculosis medications. Echocardiography found free floating multiple discoid masses in the pericardial effusion. The masses and exudates were removed by pericardiostomy. The masses were composed of pink, amorphous meshwork of threads admixed with degenerated red blood cells and leukocytes with numerous acid-fast bacilli, which were confirmed as Mycobacterium species by polymerase chain reaction. The persistent fever and anemia were controlled after pericardiostomy. This is the report of a unique manifestation of Tb pericarditis as free floating masses in the effusion with impending tamponade.
Pericarditis; Tuberculosis; Pericardial Effusion; Cardiac Tamponade
The most prevalent severe manifestation of systemic lupus erythematosus (SLE) is nephritis which is characterized by immune complex deposition, inflammation, and scarring in both glomeruli and in the tubulointerstitium. Numerous studies indicate that glomerulonephritis results from a systemic break in B cell tolerance resulting in the local deposition of immune complexes containing antibodies reactive with ubiquitous self-antigens. However, the pathogenesis of SLE tubulointerstitial disease is not known. Herein, we demonstrate that in over half of a cohort of 68 lupus nephritis biopsies, the tubulointerstitial infiltrate was organized into either well-circumscribed T:B cell aggregates or germinal centers (GCs) containing follicular dendritic cells. Sampling of the in situ expressed immunoglobulin repertoire revealed that both histological patterns were associated with intrarenal B cell clonal expansion and ongoing somatic hypermutation. However, in the GC histology the proliferating cells were CD138−CD20+ centroblasts while in T:B aggregates, they were CD138+CD20low/− plasmablasts. The presence of either GCs or T:B aggregates was strongly associated with tubular basement membrane immune complexes. These data implicate tertiary lymphoid neogenesis in the pathogenesis of lupus tubulointerstitial inflammation.
B cells; somatic hypermutation; human; nephritis; systemic lupus erythematosus; tertiary lymphoid neogenesis; plasmablasts
Thrombotic thrombocytopenic purpura (TTP) is a multisystemic disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, which may be accompanied by fever, renal, or neurologic abnormalities. Cases are divided into acute idiopathic TTP and secondary TTP. Autoimmune diseases, especially systemic lupus erythematosus, in association with TTP have been described so far in many patients. In contrast, TTP occurring in a patient with mixed connected tissue disease (MCTD) is extremely rare and has only been described in nine patients. We describe the case of a 42-year-old female with MCTD who developed thrombocytopenia, microangiopathic hemolytic anemia, fever, and neurological symptoms. The patient had a good clinical evolution with infusion of high volume of fresh frozen plasma, steroid therapy, and support in an intensive care unit. Although the occurrence of TTP is rare in MCTD patients, it is important to recognize TTP as a cause of thrombocytopenia and hemolytic anemia in any patient with autoimmune diseases. Prompt institution of treatment remains the cornerstone of treatment of TTP even if plasma exchange is not available like what frequently happens in developing countries.
A 37-year-old male presented with fever and jaundice was diagnosed as hepatitis A complicated with progressive cholestasis and severe autoimmune hemolytic anemia. He was treated with high-dose prednisolone (1.5 mg/kg), and eventually recovered. His initial serum contained genotype IA hepatitis A virus (HAV), which was subsequently replaced by genotype IIIA HAV. Moreover, at the time of development of hemolytic anemia, he became positive for immunoglobulin M (IgM) anti-hepatitis E virus (HEV). We detected HAV antigens in the liver biopsy specimen, while we detected neither HEV antigen in the liver nor HEV RNA in his serum. This is the first report of hepatitis A coinfected with two different genotypes manifesting with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive IgM anti-HEV.
Hepatitis A virus; Genotype; Coinfection; Hemolytic anemia; Korea