Pauci-immune Glomerulonephritis Research Articles

Association of Silica Exposure with Anti–Neutrophil Cytoplasmic Autoantibody Small-Vessel Vasculitis

Anti-neutrophil cytoplasmic autoantibodies (ANCA) are associated with a category of small-vessel vasculitis (SVV) with frequent glomerulonephritis. The goal of this study was to evaluate the association of lifetime silica exposure with development of ANCA-SVV, with particular attention to exposure dosage, intensity, and time since last exposure. A southeastern United States, population-based, case-control study was conducted. Case patients had ANCA-SVV with pauci-immune crescentic glomerulonephritis. Population-based control subjects were frequency-matched to case patients by age, gender, and state. Jobs were assessed in a telephone interview. Silica exposure scores incorporated exposure duration, intensity, and probability for each job and then were categorized as none, low/medium, or high lifetime exposure. Logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Silica exposure was found in 78 (60%) of 129 case patients and in 49 (45%) of 109 control subjects. There was no increased risk for disease from low/medium exposure relative to no exposure (OR 1.0; 95% CI 0.4 to 2.2) but increased risk with high exposure (OR 1.9; 95% CI 1.0 to 3.5; P = 0.05). Crop harvesting was associated with elevated risk (OR 2.5; 95% CI 1.1 to 5.4; P = 0.03). However, both agricultural and traditional occupational sources contributed to the cumulative silica exposure scores; therefore, the overall effect could not be attributed to agricultural exposures alone. There was no evidence of decreasing by duration of time since last exposure. High lifetime silica exposure was associated with ANCA-SVV. Exposure to silica from specific farming tasks related to harvesting may be of particular importance in the southeastern United States. Interval of time since last exposure did not influence development of ANCA-SVV.

Bench-to-bedside review: pulmonary-renal syndromes--an update for the intensivist.

The term Pulmonary–renal syndrome refers to the combination of diffuse alveolar haemorrhage and rapidly progressive glomerulonephritis. A variety of mechanisms such as those involving antiglomerular basement membrane antibodies, antineutrophil cytoplasm antibodies or immunocomplexes and thrombotic microangiopathy are implicated in the pathogenesis of this syndrome. The underlying pulmonary pathology is small-vessel vasculitis involving arterioles, venules and, frequently, alveolar capillaries. The underlying renal pathology is a form of focal proliferative glomerulonephritis. Immunofluorescence helps to distinguish between antiglomerular basement membrane disease (linear deposition of IgG), lupus and postinfectious glomerulonephritis (granular deposition of immunoglobulin and complement) and necrotizing vasculitis (pauci-immune glomerulonephritis). Patients may present with severe respiratory and/or renal failure and require admission to the intensive care unit. Since the syndrome is characterized by a fulminant course if left untreated, early diagnosis, exclusion of infection, close monitoring of the patient and timely initiation of treatment are crucial for the patient's outcome. Treatment consists of corticosteroids in high doses, and cytotoxic agents coupled with plasma exchange in certain cases. Renal transplantation is the only alternative in end-stage renal disease. Newer immunomodulatory agents such as those causing TNF blockade, B-cell depletion and mycophenolate mofetil could be used in patients with refractory disease.

Cytoplasmic antineutrophil cytoplasmic antibody positive pauci-immune glomerulonephritis associated with infectious endocarditis

Renal deterioration often occurs in cases of infectious endocarditis (IE), but, IE- associated nephritis with rapidly progressive glomerulonephritis (RPGN) is rare. Patients with severe infection (e.g., IE) sometimes show positivity for cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA). Therefore, diagnosis and treatment are very difficult in cases of RPGN with IE and positivity for C-ANCA. Such cases are rare, only 12 have been reported in the English literature. Herein, we describe the case of a 50-year-old man who presented with RPGN with IE and tested positively for C-ANCA. He was referred to our hospital because of leg edema, purpura and renal dysfunction. Laboratory tests revealed serum creatinine elevation and positivity for C-ANCA and proteinase 3-specific (PR3)-ANCA. RPGN and acute renal failure were diagnosed. Hemodialysis and steroid therapy were started. Streptococcus oralis was isolated by blood culture. Transthoracic echocardiography revealed grade III mitral valve insufficiency with two vegetations. Therefore, IE was diagnosed. The steroid therapy was stopped, and antibiotic therapy was begun. Because there was no improvement, surgical therapy was performed. The operation was successful, but the patient died of brain hemorrhage. Our experience in this case indicates C/PR3-ANCA positive RPGN must be ruled out in patients with infectious disease, particularly IE, together with renal symptoms, and renal biopsy should be performed.

Up-regulation of adhesion molecule expression in glomerular endothelial cells by anti-myeloperoxidase antibody

Anti-neutrophil cytoplasmic antibody directed against myeloperoxidase (MPO-ANCA) has been implicated in pauci-immune crescentic glomerulonephritis. It stimulates primed neutrophils to adhere to glomerular endothelial cells (GECs), thereby releasing reactive oxygen and other toxic substances and ultimately damaging the GECs. Though, a pathogenic role for MPO-ANCA is not fully understood, we hypothesized that MPO-ANCA modulates GEC functions by the increases in expression of adhesion molecules. A polyclonal rabbit anti-recombinant mouse MPO antibody (anti-rmMPO IgG) was evaluated in mouse GEC (mGEC) for its effect on adhesion molecule expression. The primary culture of mGEC was incubated with anti-rmMPO IgG or isotype control and the expression of intercellular adhesion molecules-1 (ICAM-1) was evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis and ICAM-1 cell ELISA. The real-time RT-PCR analysis showed that a treatment with 100 microg/ml anti-rmMPO IgG increased the expression of mRNAs for ICAM-1, vascular cell adhesion molecule-1 and E-selectin by approximately 12.5, 7.5 and 10.5-fold, respectively. ICAM-1 cell ELISA also substantiated increased expression of ICAM-1. This enhancement of ICAM-1 expression was mediated by the antigen specificity of anti-rmMPO IgG. In addition, there were several proteins in mGEC specifically immunoprecipitated with anti-rmMPO IgG. These results showed that anti-MPO antibody activates not only neutrophils, but also GEC, indicating that anti-rmMPO IgG-induced direct activation of GEC contributes to neutrophil adhesion to GEC, thereby increasing glomerular neutrophil infiltration in initiation and progression of pauci-immune glomerulonephritis.

Wegener Granulomatosis Mimicking Inflammatory Bowel Disease in a Pediatric Patient

Wegener Granulomatosis Mimicking Inflammatory Bowel Disease in a Pediatric Patient

PR3-ANCA-positive crescentic necrotizing glomerulonephritis accompanied by isolated pulmonic valve infective endocarditis, with reference to previous reports of renal pathology

Patients with infective endocarditis (IE) often have renal complications which may include infarcts, abscesses and glomerulonephritis (GN). Furthermore, it is generally accepted that there is an association between IE and anti-neutrophil cytoplasmic antibody (ANCA). Here, we report the case of a 24-year-old man who developed rapidly progressive GN in the course of IE due to infection with alpha-streptococcus. The initial clinical manifestation of the condition was severe sacroiliitis without fever. Sandwich ELISA showed that the patient was positive for PR3-ANCA at low titer, and the classical complement pathway was also activated. Renal biopsy demonstrated several lesions: focal embolic GN, GN with immune deposits and focal and segmental crescentic necrotizing GN. Treatment with antibiotics and steroids led to eradication of the infection, and resolution of the renal disease was accompanied by immediate disappearance of PR3-ANCA and hypocomplementemia. During a 4-year follow-up period, no recurrence was observed. There have only been 7 case reports of GN associated with IE and PR3-ANCA in which the renal pathology has been described, and the current report is the first to document renal pathology in a patient with isolated pulmonic valve IE and PR3-ANCA. Moreover, this report is the first to show a change in renal biopsy findings in response to treatment. A review of the 7 literature cases and that of our patient showed that none involved pauci-immune GN. Hence, further studies are needed to clarify the prevalence of pauci-immune GN in ANCA-positive IE patients.

Poor Renal Outcome of Antineutrophil Cytoplasmic Antibody Negative Pauci-immune Glomerulonephritis in Taiwanese

Pauci-immune glomerulonephritis (GN) is an important cause of crescentic GN, acute renal failure and mortality. However, data are limited on the clinical presentation and outcome in antineutrophil cytoplasmic antibody (ANCA) negative patients, especially in Asians. This retrospective study analyzed medical records and pathology slides of patients who received renal biopsy between February 1998 and October 2004. Enzyme-linked immunosorbent assay was used routinely for ANCA testing in all patients. Among 637 patients with biopsy-proven GN included in this study, 88 (13.8%) had glomerular crescent formation. Among them, pauci-immune crescentic glomerulonephritis (PICGN) (42 patients, 47.2%) and lupus nephritis (25 patients, 28.4%) were the most common pathologic diagnoses. Lupus patients were younger (p = 0.028), while PICGN patients had more chronic lesions (p < 0.001), extensive glomerular crescents (p < 0.001), less severe proteinuria (p < 0.001) and poorer renal survival (p = 0.0017). Among the PICGN patients, 62.5% had a positive ANCA test, 80% had myeloperoxidase-ANCA and 20% had proteinase-3-ANCA. Subgroup analysis showed that ANCA negativity was associated with less crescent formation (p < 0.001) but more chronic glomerular lesions (p < 0.001) and a trend toward worse renal outcome (p = 0.055). This study illustrates the necessity for pathologic diagnosis of pauci-immune GN despite ANCA negativity. The poor prognosis associated with ANCA negativity in this study may be partly due to delayed diagnosis since these patients frequently lacked systemic involvement.

Necrotic Vasculitis in a Patient with Abdominal Fibromatosis and Guillain-Barré Syndrome

The case of a 65-year-old woman presenting with Guillain-Barré syndrome is herein reported. Tomographic investigation revealed abdominal and retroperitoneal fibromatosis. During her hospitalization, renal involvement ensued, and subsequent renal biopsy demonstrated findings of crescentic pauci-immune glomerulonephritis negative for ANCA antibodies and with characteristics indicative of necrotic angiitis. The simultaneous existence of the three diseases in the same patient as well as the relation between necrotic vasculitis and G-B syndrome is speculated, and the relevant literature is reviewed.

The epidemiology of Wegener's granulomatosis and microscopic polyangiitis in a Southern Hemisphere region

To determine the prevalence of Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) in the province of Canterbury, New Zealand. Three hospital clinical databases and the immunology laboratory database were searched and case notes reviewed for patients fulfilling either the 1990 American College of Rheumatology (ACR) criteria for WG or a modification of those criteria that allowed for antineutrophil cytoplasmic antibody (ANCA) positivity in the absence of granulomatous vasculitis. MPA was defined by the Chapel Hill consensus definition; however, in the absence of histological evidence of pauci-immune glomerulonephritis, ANCA positivity in association with evidence of active glomerular disease was included as a criterion. The point prevalence at 31 December 2003 and the 5-yr period prevalence for the interval 1 January 1999 to 31 December 2003 were calculated. Seventy-three patients with WG and 28 patients with MPA fulfilled the inclusion criteria. A 5-yr period prevalence of 152 WG cases/million [95% confidence interval (CI) 117-186] and 58 MPA cases/million (95% CI 37-80) was calculated using 2001 census data as denominator. Nineteen patients with WG died and 10 patients with MPA died during the study period, resulting in a point prevalence for survivors at 31 December 2003 of 112 cases/million (95% CI 82-142) and 37 cases/million (95% CI 20-55), respectively. Using unmodified ACR criteria the 5-yr period and point prevalence for WG were 131/million (95% CI 99-163) and 93.5/million (95% CI 66-121), respectively. Apart from respiratory tract involvement, which formed part of the case definition of WG, organ involvement was similar in both diseases. The prevalence of WG and MPA in Canterbury is the highest reported to date. Restricting the case definition of WG to the ACR classification criteria we found a prevalence equivalent to that described in northern Norway. The clinical severity and serological characteristics were similar to descriptions in other WG and MPA patient cohorts. Studies of disease prevalence in other Southern Hemisphere centres will determine if the observed north-south negative disease gradient in the Northern Hemisphere is reciprocated.

Urgences médicales et complications graves des vascularites

Severe and life-threatening manifestations may occur in each of the systemic vasculitides, at the onset of the disease or during a subsequent flare, but may also be due to a side effect of immunosuppressive therapy. Heart involvement is the primary cause of death for Kawasaki disease and Churg-Strauss syndrome, while severe gastrointestinal manifestations (perforations, peritonitis) are the main cause of mortality for polyarteritis nodosa. Central nervous system involvement (multifocal or diffuse leucoencephalopathy, stroke) is rare but has a poor prognostic value. Pauci-immune necrotizing and crescentic glomerulonephritis, with rapidly-progressive renal failure, is the most typical kidney manifestation and is one of the primary motives for admission in Intensive Care Units for these patients. Alveolar hemorrhage is a characteristic, although non-specific, lung manifestation of Wegener's granulomatosis and microscopic polyangiitis. Patients may also have other life-threatening complications, due to vasculitis, like subglottic or bronchial stenoses or malignant hypertension, or related to an adverse event of immunosuppressants, mainly infections and/or allergic reactions, like interstitial pneumonitis. Therapeutic choices are based upon validated trials and criteria, like the prognostic Five Factor Score. Indeed, prompt and adequate therapeutic decisions have to be made in order to improve the outcome of these most severely ill patients.

Vascularite familiale des vaisseaux de petit calibre des reins

Familial forms of small-vessel vasculitis has been reported in 14 families (including this one). A father and son were both diagnosed with renal vasculitis (pauci-immune crescentic glomerulonephritis). Both had antimyeloperoxidase autoantibodies, and there was no evidence of a common environmental factor. These cases suggest the role of constitutional factors in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis.

The Role of Neutrophils in the Induction of Glomerulonephritis by Anti-Myeloperoxidase Antibodies

In humans, circulating anti-neutrophil cytoplasm autoantibodies (ANCAs) with specificity for myeloperoxidase (MPO) are strongly associated with the development of pauci-immune necrotizing and crescentic glomerulonephritis (NCGN). In mice, we have demonstrated that intravenous injection of mouse antibodies specific for mouse MPO induces NCGN that closely mimics the human disease. We now report that the development of NCGN in this experimental model is accompanied by glomerular accumulation of neutrophils and macrophages. Neutrophil infiltration was most conspicuous at sites of glomerular necrosis and crescent formation, with macrophages also most numerous in crescents. Lymphocytes, however, were sparse in acute lesions. Importantly, mice that were depleted of circulating neutrophils with NIMP-R14 rat monoclonal antibodies were completely protected from anti-MPO IgG-induced NCGN. These findings provide direct evidence that neutrophils play a major role in the pathogenesis of anti-MPO-induced NCGN in this animal model and implicate neutrophils in the induction of human ANCA disease. This raises the possibility that therapeutic strategies to reduce circulating neutrophils could be beneficial to patients with ANCA-induced NCGN.

ANCA-negative pauci-immune crescentic glomerulonephritis complicated with recurrent massive gastrointestinal hemorrhage

On April 25, 2003, a 62-year-old Japanese man had been admitted to a hospital because of heavy proteinuria and elevated serum creatinine level, and purpura on the lower extremities. On May 15, 2003, he was referred to our hospital for evaluation and treatment. Serum immunoglobulin and complements were within normal ranges. Immune serology was negative for antinuclear antibody, antiglomerular basement membrane antibody, and antineutrophil cytoplasmic antibodies. Histological examination of a percutaneous renal biopsy specimen revealed that all of the glomeruli had severe crescent formation without deposits of immunoreactants. A diagnosis of antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis was made. The patient was treated with one cycle of steroid pulse therapy (1000 mg methylprednisolone daily, given on 3 consecutive days), and subsequently with prednisolone (60 mg/day). Despite this treatment, renal failure progressed rapidly and hemodialysis was started 1 month after the acute presentation. On May 30, 2003, he suddenly developed massive hematochezia. A technetium-targeted red-blood-cell scan suggested bleeding in the small intestine. On June 11, he presented with massive melena. A bleeding ulcer was found in the third part of the duodenum, and was treated successfully with endoscopy, using a heater probe. On June 19, he presented with massive hematochezia again. Mesenteric angiography revealed active bleeding from the iliac branch of the superior mesenteric artery. He was treated with continuous intraarterial vasopressin infusion by a catheter seated in the branch artery. The majority of patients with pauci-immune crescentic glomerulonephritis, one of the most common causes of rapidly progressive glomerulonephritis, have glomerular disease as part of a systemic vasculitis. Massive gastrointestinal bleeding, although rare, should be considered one of the serious complications in these patients.

Development of glomerulonephritis during anti-TNF-α therapy for rheumatoid arthritis

Treatment of rheumatoid arthritis with anti-tumour necrosis factor alpha (TNFalpha) agents may lead to autoantibody formation and flares of vasculitis, but renal complications are rare. We report the clinical and pathologic findings in five patients with longstanding rheumatoid arthritis (duration of rheumatoid arthritis, 10-30 years; mean, 23 years) who developed new onset of glomerular disease after commencing therapy with anti-TNFalpha agents (duration of therapy, 3-30 months; median, 6 months). At presentation, three patients were receiving etanercept, one adalimumab and one infliximab. Two subjects presented with acute renal insufficiency, haematuria, nephrotic-range proteinuria, positive lupus serologies, and hypocomplementemia, and renal biopsies showed proliferative lupus nephritis. Two individuals presented with new onset renal insufficiency, haematuria and proteinuria, and renal biopsies showed pauci-immune necrotizing and crescentic glomerulonephritis. One of these subjects, who had anti-myeloperoxidase autoantibodies, also developed pulmonary vasculitis. The fifth patient presented with nephrotic syndrome and renal biopsy findings of membranous glomerulonephritis, associated with immune complex renal vasculitis. A pathogenic role for anti-TNFalpha therapy is suggested by the close temporal relationship with development of glomerular disease, and by the improvement in clinical and laboratory abnormalities after drug withdrawal and initiation of immunosuppressive therapy in most cases. Rheumatoid arthritis patients receiving anti-TNFalpha agents may develop glomerulonephritis via the induction of rheumatoid arthritis-related nephropathy or de novo autoimmune disorders.

A rare lung manifestation with rapidly progressive glomerulonephritis (RPGN)

In this unusual case, we report the history of a patient who was hospitalized with pulmonary manifestations presenting as broncholitis obliterance organizing pneumonia (BOOP) associated with ANCA-negative pauci-immune glomerulonephritis. Other known causes for the occurrence of BOOP were excluded. Immediate diagnosis and treatment with a combination of steroids and cytotoxic therapy resulted in a complete remission and prevented eventual dialysis.

Apheresis for MPO-ANCA-associated RPGN—indications and efficacy: Lessons learned from Japan nationwide survey of RPGN

A national survey concerning rapidly progressive glomerulonephritis (RPGN) was conducted in Japan between 1989 and 2000 and resulted in the registration of 715 patients with RPGN. Among the documented patients, the most frequent primary disease was primary pauci-immune crescentic glomerulonephritis (n = 283), and the second most frequent was microscopic polyangitis (n = 127). Overall, 370 patients had MPO-ANCA, and 23 patients had PR3-ANCA. We found that both renal and patient survivals were significantly worse in patients with MPO-ANCA-associated RPGN than patients with PR3-ANCA. Fifty-three patients received apheresis therapy with various combinations of immunosuppressive regimens. They had higher serum creatinine, higher CRP, and a higher frequency of complicated pulmonary involvements as compared to the controls without apheresis therapy. In dialysis-dependent patients, no additional benefit from apheresis therapy was observed. Only pulmonary renal syndrome patients with CRP > 6 mg/dl at presentation showed a slightly better prognosis (patient survival with apheresis; 66.7%, without apheresis; 56.7%). Furthermore, a rapid MPO-ANCA titer reduction was observed in patients treated with apheresis. Patients with MPO-ANCA-associated RPGN were older, and had more chronic and sclerotic lesions than patients with PR3-ANCA-associated RPGN. Based on these findings, we suggest that a lower dose of immunosuppressant should be considered in order to avoid opportunistic infection. In this situation, cytapheresis is the treatment of choice. Nevertheless, in patients with an aggressive form of RPGN with rapid deterioration of renal function like the PR3-ANCA-associated RPGN, or pulmonary renal syndrome complicated severe inflammation, or relapses with high MPO-ANCA titer, we conclude that apheresis therapy should be considered.

An unusual endocarditis-induced crescentic glomerulonephritis treated by plasmapheresis

A 58-year-old man presented with fever and a rapidly progressive glomerulonephritis. An infective endocarditis due to Streptococcus parasanguis was diagnosed. A renal biopsy revealed type III pauci-immune crescentic glomerulonephritis. As first-line therapy, antibiotics were administered alone. Faced to the unsuccessful anti-infective approach, corticosteroid therapy was added as a second-line therapy. Finally, plasmapheresis introduced as the third-line therapy, significantly improved renal function. This case is an original type III rapidly progressive glomerulonephritis, since ANCA were repeatedly found negative. In very few cases, plasmapheresis was successfully used for the treatment of infective endocarditis-induced crescentic glomerulonephritis. The pathophysiology and the potential efficiency of plasmapheresis are discussed.

Temporal arteritis with pauci-immune glomerulonephritis: a systemic disease

Temporal arteritis is easily diagnosed and responds gratifyingly to treatment. Renal complications are unusual, but nevertheless occur. Earlier, an association between pauci-immune glomerulonephritis and temporal arteritis was shown. We present a patient who clearly had temporal arteritis but also developed cerebral hemorrhage, pulmonary infiltrates related to granulomatous pulmonary vasculitis, and pauci-immune glomerulonephritis. We suggest that temporal arteritis is neither always localized nor temporal. Instead, the condition can be a lethal, systemic disease. Renal involvement in patients with temporal arteritis is not common and the presence of glomerulonephritis is rare [Jennette and Falk 1994]. Lenz et al. [1998] described a patient who developed vision loss, optic nerve atrophy, elevated erythrocyte sedimentation rate, a positive rheumatoid factor and terminal glomerulonephritis. The renal biopsy showed focal and segmental necrotizing glomerulonephritis, despite negative antineutrophil cytoplasmatic antibodies (ANCA), antinuclear antibodies and antiglomerular basement membrane antibodies. Giant cells were identified in the necrotic vessel walls within the kidney. Immunofluorescence was negative and a diagnosis of ANCA-negative pauci-immune glomerulonephritis was made. The patient did not respond to immunosuppression and developed end-stage renal disease. Although the clinical attributes were consistent with temporal arteritis, no temporal artery biopsy was done in that patient. We recently treated a patient with temporal arteritis and pauci-immune glomerulonephritis. Our patient's course was somewhat different in comparison to the patient described by Lenz et al. [1998].

Antineutrophil cytoplasmic antibodies in patients with Graves’ disease: association of antimyeloperoxidase autoantibodies with propylthiouracil therapy

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitic disorders have been reported in patients with Graves’ disease during propylthiouracil (PTU) therapy. To investigate whether ANCA are found in serum samples from patients with Graves’ disease, and whether PTU therapy is associated with ANCA positivity, levels of serum ANCA were examined in Graves’-disease patients receiving either PTU (n = 49) or 1-methyl-2-mercaptoimidazole (methimazole, MMI) (n = 50), and in untreated Graves’-disease patients (n = 32) by enzyme-linked immunosorbent assay (ELISA). Serum samples from patients with Hashimoto’s thyroiditis (n = 46) were also analyzed. Antimyeloperoxidase (MPO) autoantibodies (MPO-ANCA) were present in 10 (20.4%) of 49 Graves’-disease patients receiving PTU therapy, whereas MPO-ANCA were not detected in Graves’-disease patients receiving MMI, in untreated Graves’-disease patients, or in Hashimoto’s thyroiditis patients. The MPO-ANCA-positive sera showed a perinuclear staining pattern which was detected by indirect immunofluorescence microscopy using a human polymorphonuclear leukocyte–cytospin preparation. Furthermore, Western blot analysis revealed that MPO-ANCA in the Graves’-disease patients, as well as MPO-ANCA in patients with idiopathic pauci-immune necrotizing and crescentic glomerulonephritis, recognize the 105-kD protein of native MPO. These results indicate that MPO-ANCA in Graves’-disease patients are strongly associated with PTU therapy, and not simply related to the autoimmune thyroid disease. This study also suggests that the presence of MPO-ANCA alone may not be sufficient for the development of vasculitic disorders.

Acute pancreatitis and exacerbation of hepatitis B following reduced dose of prednisolone

Sir, Hepatitis virus type B (HBV) infects the pancreas1,,2 and may cause acute pancreatitis.1–,5 Immunosuppressive therapy results in enhanced replication of HBV and depressed host immunity. The discontinuation of therapy causes a rebound of the immune system, resulting in development of hepatitis. Here, we report a patient with underlying HBV infection, who had acute/non-fluminant hepatitis with acute pancreatitis after a decrease in dose of an immunosuppressive agent. A 48-year-old Japanese male HBV carrier (HB surface antigen-positive) was diagnosed with Graves’ disease, and was treated with propylthiouracil 300 mg/day. After 8 days treatment, he developed a high fever. Examination revealed glomerular nephritis associated with positive perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). The serum titre of p-ANCA was 179 IU/ml. Renal biopsy showed a crescentic glomerulonephritis. Propylthiouracil has been reported to be associated with ANCA-positive pauci-immune glomerulonephritis, and was therefore …