Granular Deposits Of Immunoglobulin Research Articles

Direct Immunofluorescence in Dermatomyositis and Lupus Erythematosus: Cross-Sectional Diagnostic Accuracy and Correlation With Serologies and Other Features of Systemic Disease.

This is a retrospective cross-sectional diagnostic test accuracy study of direct immunofluorescence (DIF) performed on a group of potential lupus erythematosus (LE)/dermatomyositis (DM) skin biopsies from 2015 to 2020 at a large, academic medical center. For purposes of this study, which was focused primarily on detection of LE/DM-related interface dermatitis, DIF was considered positive for a LE/DM pattern if it showed granular deposition of immunoglobulin G, with or without C3, at the basement membrane zone on the final pathology report. Blinded clinicopathologic correlation was the reference standard. One thousand fifty-eight sequential pairs of skin biopsies obtained from adults and submitted for both DIF and routine histology were screened. Cases were excluded if histopathology did not demonstrate features that could be consistent with LE/DM (broadly predefined as interface dermatitis and/or neutrophilic dermatosis), resulting in 254 cases of possible LE/DM eruptions for further analysis. Sensitivity of DIF with an immunoglobulin G granular pattern at the basement membrane zone was 71.4% (confidence interval 55.4%-84.3%) in LE-related and 59.3% (confidence interval 38.8%-77.6%) in DM-related eruptions. No statistically significant difference was found in sensitivities of DIF between LE and DM (P = 0.3). DIF positivity did not correlate with available key demographic, clinical, and serologic features.

#4488 OLD BIOPSY IS ALWAYS GOLD, REVISING MEMBRANOPROLIFERATIVE GN DIAGNOSIS IN A RENAL TRANSPLANT PATIENT

Abstract Background and Aims MPGN resulting from hepatitis C virus (HCV) infection typically shows granular deposition of immunoglobulin M (IgM), C3, and both kappa and lambda light chains. Immunoglobulin G (IgG) may or may not be present, and C1q is typically negative, the same pathology can be found in other viral infections. The recurrence rate post-transplantation is high, with 33% of immune-complex MPGN. Graft loss is even higher 65%, especially among patients with idiopathic MPGN. Treatment of a patient with significant proteinuria can be tricky, as no proven treatment is described yet, but plasmapheresis and induction with cyclophosphamide were described for heavy proteinuria >3.5 g/day. Method 79 year old female patient, known case of live unrelated renal transplantation in December 2013, primary renal disease is unknown. She had a history of equivocal hepatitis C virus antibodies, but Hepatitis C virus RNA was not detected. She is also known to have Type II Diabetes Mellitus and hypertension. The patient had baseline creatinine of 100-120 micromol/L. 24 hr urine protein was 0.8 g/Day but started rising quickly to reach a peak of 9.2 g/g seven months post-transplantation to nephrotic range proteinuria but her serum albumin level was always above 35 g/L. Serum protein electrophoresis showed no M band, a kappa/ Lambda ratio 1.21 within a normal range (0.260-1.65). Anti- nuclear antibody (ANA), P-ANCA, C-ANCA, and Double-stranded DNA all were negative. Complements were within normal range C3 1.39 g/L (0.79 -1.52), C4 0.44 g/L(0.17-0.57)m rheumatoid factor and Anti- citrullinated peptide antibodies were negative. Hepatitis b Virus surface antigen and core antibodies were not reactive, HIV screening was negative. Urine analysis showed RBCs but no RBC casts. Renal biopsy showed mild mesangial expansion and mild l increase in mesangial cells and matrix. Some glomeruli show increased lobulation with increase in mesangial cells and matrix with segmental endocapillary proliferation There is double contour of the glomerular basement membrane with scattered spikes and holes within the basement membrane seen best with silver stain. There is mild increase in the thickness of glomerular basement membrane. There is focal mild lymphocytic infiltration. Tubulitis is not seen in the examined material. One Focal area of mild interstitial fibrosis. Sampled blood vessels are unremarkable. The stain for C4d is negative. Immunofluorescence showed granular capillary wall immunoreactivity to IgM (+2), C4 (+1), C1q (+1), and Lambda light chain (+2). The glomeruli show no immunoreactivity to IgG, IgA, C3, Kappa and fibrin. The glomeruli show (+) staining for albumin. Tubular protein reabsorption droplets showed immunoreactivity for albumin, IgG, IgM, C3, kappa and lambda light chains. Electron microscopy showed many subendothelial, and mesangial electron-dense deposits. The patient was on maintenance immunosuppression medications inform of mycophenolic acid 720 mg, cyclosporine; 250mg BID, and Prednisolone 5 mg daily.Revisiting the new classification of membranoproliferative glomerulonephritis is challenging in this patient, since there is the dominance of IgM deposition by immunofluorescence and C4 but not C3 makes it challenging, the negative monoclonal band in serum electrophoresis and negative autoimmune workup excludes immune complex mediate MPGN, leave idiopathic MPGN a possibility, keeping in mind that hepatitis C virus infection was never confirmed. On the other hand, IF showed IgM with C4 subendothelial and mesangial dense deposits that excludes away the C4 glomerulopathy. Results Whether this is a recurrence of glomerular disease early on post-transplantation or denovo membranoproliferative disease, she responded well to the addition of losartan 100 mg daily, with a reduction of her urinary protein to less than 1 g/g. the patient never received treatment for the hepatitis C virus. Conclusion In our patient, it is difficult to conclude if the cause of MPGN is recurrence or denovo GN, especially with severe proteinuria that responded well to ACEi treatment. The pathological findings can be tricky.

Cutaneous lupus: Immunofluorescence and lupus band test

Cutaneous lupus erythematosus is an autoimmune disease with a broad range of clinical findings. There are several methods to conduct a diagnostic approach, among these stands direct immunofluorescence, in which we can find the Lupus Band Test (LBT) consisting of a band of granular deposits of immunoglobulins and complement along the dermo-epidermal junction. It can have a high sensitivity and specificity for diagnosis in some cases, according to the biopsy site, the constituents of immunorreactants found at the dermoepidermal junction, and the morphology and intensity of the immunofluorescent band. Certain limitations of the test should be considered when interpreting the results. Although useful in diagnosis, the lupus band is not considered a pathognomonic sign of erythematous lupus. About one-third of patients with positive direct immunofluorescence on a skin biopsy do not have systemic lupus erythematosus (SLE). A positive LBT in non-lesional photoprotected skin represents a criterion with high specificity to identify patients with SLE.

British Association of Dermatologists guidelines for the management of people with cutaneous lupus erythematosus 2021.

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of cutaneous lupus erythematosus (CLE) in the presence or absence of systemic lupus erythematosus (SLE) in adults, young people and children. The document aims to: offer an appraisal of all relevant literature up to December 2020, focusing on any key developments address important, practical clinical questions relating to the primary guideline objective. provide guideline recommendations and if appropriate research recommendations.

Missing Insight Into T and B Cell Responses in Dermatitis Herpetiformis.

Dermatitis herpetiformis is a cutaneous form of celiac disease manifesting as an itching rash typically on the elbows, knees and buttocks. It is driven by the ingestion of gluten-containing cereals and characterized by granular deposits of immunoglobulin A in the papillary dermis. These antibodies target transglutaminase (TG) 3 and in the majority of patients they are also found in circulation. The circulating antibodies disappear and skin symptoms resolve as a result of gluten-free diet but the cutaneous anti-TG3 IgA deposits may persist for several years. In dermatitis herpetiformis, plasma cells secreting antibodies against TG3 are located in the intestinal mucosa similarly to those producing TG2 antibodies characteristic for celiac disease. In fact, both TG2- and TG3-specific plasma cells and gluten responsive T cells are found in dermatitis herpetiformis patients but the interplay between these cell populations is unknown. The small bowel mucosal damage in celiac disease is believed to be mediated by co-operation of cytotoxic intraepithelial T cells and the inflammatory milieu contributed by gluten-reactive CD4+ T cells, whereas the skin lesions in dermatitis herpetiformis appear to be devoid of gluten reactive T cells. Thus, how celiac disease-type intestinal T and B cell responses develop into an autoimmune condition affecting the skin is still incompletely understood. Finally, the skin and small bowel lesions may reappear upon reintroduction of gluten in patients treated with gluten-free diet but virtually nothing is known about the long-lived B cell and memory T cell populations activating in response to dietary gluten in dermatitis herpetiformis.

The need for a multidisciplinary approach to the diagnosis and treatment procedures of isolated lesions of the oral mucosa in herpetiform Dühring dermatitis

The defeat of the oral mucosa in herpetiform Dhring dermatitis is a rare pathology. According to the literature, it is detected in 9.6% 10% of cases. Granular deposits of immunoglobulin A in the papillae of the dermis in herpetiform Dhring dermatitis are associated with gluten enteropathy, lead to the development of inflammatory processes on the skin and oral mucosa and the appearance of polymorphic itchy rashes and chronic recurrent course of the disease. The article describes a clinical case of a patient diagnosed with herpetiform dermatitis, manifestations in the oral cavity (ICD-10 L13.0X code). The need for a multidisciplinary approach to the diagnosis, differential diagnosis, treatment and dynamic observation of isolated lesions of the oral mucosa in herpetiform Dhring dermatitis is indicated. A scheme of measures required by a dentist is developed.

S0862 Increased Prevalence of Dermatitis Herpetiformis Among Patients With IBD Without Concomitant Celiac Disease: Results From a Population-Based Study

INTRODUCTION: Dermatitis herpetiformis (DH) is an autoimmune eruption of pruritic inflammatory papules and vesicles that occur in a grouped arrangement on different parts of the body. It is characterized by granular deposits of immunoglobulin A (IgA) within the dermal papillae on immunofluorescence. Previous case studies (Alonso-Llamazares et al) and case reports have described an association between DH and ulcerative colitis, possibly arising due to an increased permeability of intestinal mucosal barrier in inflammatory bowel disease (IBD) that allows antigen to circulate in the blood and triggering IgA antibodies. Using a large database, we sought to describe the epidemiology and risk of DH in IBD patients. METHODS: We used a commercial database (Explorys Inc, Cleveland, OH), an aggregate of Electronic Health Record data from 26 US healthcare systems. We identified a cohort of patients with IBD, celiac disease and a diagnosis of DH between June 2015 and 2020. Patients were identified based on a Systemized Nomenclature of Medicine Clinical Terms. We calculated the prevalence of DH in patients with IBD, with celiac, general population, and in individuals with neither IBD nor celiac which served as controls. RESULTS: Out of the 39,212,680 patients active from 2015 to 2020, we identified a total of 5,240 patients with DH (0.013%), 280,460 patients with IBD (0.71%), and 115,020 patients with celiac disease (0.29%). Among those with DH, there were 1290 patients diagnosed with celiac disease (without IBD), 120 patients with IBD (without CD), 60 patients with both celiac and IBD, and 3770 patients with neither celiac nor IBD (control group). The prevalence of DH was 1.12% in celiac disease (without IBD) and 0.043% in IBD (without CD). The prevalence of DH among those without celiac nor IBD (in the control group) was 0.0096%. The risk of DH was higher in celiac [OR 116.6 (109.4–124.2)] and in IBD [OR 4.41 (3.68–5.29)] compared to individuals with neither IBD nor celiac. In the cohort with IBD, risk of DH was higher in females compared to males [OR 3.06 (1.77–5.30)], in elderly patients compared to adults aged 18–65 [4.0 (2.34–6.84)], and in Caucasians compared to non-Caucasians (OR 25.0 [12.7–49.3]). CONCLUSION: Using a large population database, we described the epidemiology and risk of DH in IBD patients. We found that the risk of DH is increased in patients with IBD, consistent with prior case series. Further studies are needed to confirm this association and elucidate the mechanism behind this association.Table 1.: Odd’s ratio comparing the prevalence of dermatitis herpetiformis in celiac disease and in IBD to patients with DH without celiac or IBDTable 2.: Gender-, Age- and Race-Based Prevalence of dermatitis herpetiformis in individuals with IBD in the United States between 2015 and 2020

A case of denosumab-associated membranous nephropathy in a patient with rheumatoid arthritis.

We herein report a case of anti-RANKL monoclonal antibody-associated membranous nephropathy (MN). A 67-year-old woman with a history of rheumatoid arthritis treated with prednisolone and methotrexate for more than 30years and osteoporosis treated with eldecalcitol and teriparatide for 4years had achieved a stable disease condition. Her kidney function was normal and her urinalysis was negative for hematuria and proteinuria. An anti-RANKL monoclonal antibody (denosumab) was administered for the treatment of osteoporosis. Four months later, proteinuria appeared (2.3g/g creatinine) and remained positive for about 6months, therefore, she was admitted to our hospital. An immunofluorescence study revealed fine granular deposits of immunoglobulin G (IgG) and C3 along the capillary walls. Staining for IgG subclasses showed positive staining for IgG1 (3+), IgG2 (1+), IgG3 (1+), and IgG4 (1+); phospholipase A2 receptor was negative. Electron microscopy showed partial subepithelial and intramembranous deposits and focal thickening of the glomerular basement membrane. No evidence of malignancy or infectious disease was seen. After cessation of denosumab, the proteinuria gradually improved. Based on the renal biopsy results and clinical course (development of marked proteinuria in the presence of denosumab with subsequent amelioration in the absence of the drug), we diagnosed the patient with secondary MN due to denosumab. This is the first reported case of denosumab-associated MN.

Clinicopathological analysis of allogeneic hematopoietic stem cell transplantation–related membranous glomerulonephritis

Allogeneic hematopoietic stem cell transplantation (HSCT)-related membranous glomerulonephritis (MGN) is poorly understood. A total of 830 patients who underwent HSCT at Toranomon Hospital from 2000 to 2012 were evaluated retrospectively, including 621 patients receiving umbilical cord blood transplantation (UCBT) and 208 patients receiving unrelated bone marrow transplantation. MGN was diagnosed in 5 patients after UCBT (versus none after bone marrow transplantation) and occurred concomitantly with chronic graft-versus-host disease after cessation of immunosuppression. Light microscopy did not show any definite spikes or bubbling of the glomerular basement membrane (GBM) in all 5 patients. In 1 patient (case 5), endocapillary proliferative lesions with fibrin-like deposits were noted in addition to MGN findings. Immunofluorescence demonstrated granular deposits of immunoglobulin G (IgG; IgG1 and IgG4) along the GBM with negativity for C3, C4, and C1q in 4 patients (cases 1-4), whereas case 5 showed positivity for IgG (IgG1, IgG2, IgG3, and IgG4) as well as for C3, C4, and C1q. Electron microscopy revealed electron-dense deposits in the subepithelial space of the GBM in cases 1-4. In case 5, electron-dense deposits were present in the mesangium and the subendothelial space of the GBM, as well as in the subepithelial space. After treatment with immunosuppressants (prednisolone and/or cyclosporin) or angiotensin-converting enzyme inhibitors, complete remission with disappearance of proteinuria was achieved 12.2 months in all 5 patients, but nephrotic-range proteinuria relapsed in 2 patients during follow-up. Serum anti-PLA2R autoantibody was negative in 3 patients. HSCT-related MGN only occurred after UCBT. We believe that there were 2 morphologic patterns: early MGN and membranoproliferative pattern glomerulonephritis.

Erythema elevatum diutinum in association with dermatitis herpetiformis

Erythema elevatum diutinum (EED) is a rare skin disease that initially presents as leucocytoclastic vasculitis and later resolves with fibrosis. Dermatitis herpetiformis is an autoimmune blistering disease characterized by granular deposits of immunoglobulin A (IgA) in dermal papillae. We report a rare association of these two disorders.

'Clues' for the histological diagnosis of tinea: how reliable are they?

'Clues' for the histological diagnosis of tinea: how reliable are they?

Membranous nephropathy in an HIV-positive patient complicated with hepatitis B virus infection

In ordinary settings, human immunodeficiency virus (HIV)-associated nephropathy should be considered when HIV infection is associated with heavy proteinuria. On the other hand, hepatitis B virus (HBV) may also play a role in the development of glomerular injury among patients with HIV infection, since HIV and HBV infections commonly occur together due to shared modes of transmission. We present here a case of nephrotic syndrome in an HIV-positive patient complicated with HBV infection. A renal biopsy revealed sparse granular deposits of immunoglobulin G in the subepithelial region, consistent with membranous nephropathy (MN) stage I. Moreover, immunostaining exhibited weak anti-hepatitis B core activity within glomeruli. These results led us to consider that HBV-associated MN might play a role in the development of nephrotic syndrome. Although anti-viral treatment for patients with HBV-associated MN has been suggested to be clinically effective, the use of two anti-HIV agents (tenofovir and emtricitabine), both of which have anti-HBV activities, was not effective for the patient's nephrotic syndrome, despite obtaining a decrease in the serum HBV-DNA levels. A lack of prospective data suggests that many decisions on the treatment of glomerulopathies with HIV infections are potentially empirical. Obviously, further studies and accumulated clinical experience are required to better determine the pathogenesis and management of HBV-associated MN among patients with HIV infections.

Detection of myeloperoxidase in membranous nephropathy-like deposits in patients with anti-neutrophil cytoplasmic antibody–associated glomerulonephritis

Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis is usually classified as a pauci-immune type. However, it sometimes shows immune complex deposition of unknown origin. We examined the glomerular localization of myeloperoxidase by double immunofluorescence and immunoelectron microscopy in cases of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis with membranous nephropathy-like immunoglobulin G deposition to investigate the immune complex antigens in these cases. Six (35%) of the biopsy samples from 17 cases with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis showed granular deposition of immunoglobulin G along the glomerular capillary walls. Light microscopy revealed necrotizing crescentic glomerulonephritis with segmental thickening of the glomerular basement membrane. Electron microscopy showed electron-dense deposits in intramembranous and mesangial areas. However, the size and distribution of the deposits were irregular and segmental in the examined cases, unlike typical global and subepithelial lesions of membranous nephropathy. Double immunofluorescence using Alexa Fluor 594-labeled anti-myeloperoxidase antibody and fluorescein isothiocyanate-labeled anti-immunoglobulin G antibody, as well as immunoelectron microscopy using anti-myeloperoxidase antibody labeled with 25-nm gold particles revealed partial colocalization of myeloperoxidase and immunoglobulin G within the glomerular basement membrane and mesangium. In some cases of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, myeloperoxidase may form immune complexes and develop membranous nephropathy-like lesions.

Long-Term Outcome of Nephrotic Syndrome in an Allogeneic Hematopoietic Stem Cell Recipient Without Typical Features of Graft Versus Host Disease

Nephrotic syndrome (NS) is one of the chronic kidney diseases in long-term survivors of allogeneic hematopoietic stem cell transplantation (HSCT) and it has been an increasingly reported complication. Recently, Colombo et al. suggested that careful monitoring of renal function in myeloablative HSCT recipients with chronic graft-versus-host disease (cGVHD) may document the incidence of NS (1). Six cases of NS together with extensive cGVHD were reported in that retrospective study. The cumulative incidence of NS was reported to be 8% at day +1681. Additionally, Srinivasan and co-workers reported NS with a cumulative incidence of 6.1% in nonmyeloablative HSCT recipients from a related human leukocyte antigen (HLA)-compatible donor (2). In contrast to previous reports, three of seven NS cases were not associated with cGVHD. It was usually observed that NS is not improved with the reinitiation of aggressive immunosuppression and it results in progressive renal failure necessitating dialysis. We would like to present our experience regarding the incidence and outcome of NS in patients who underwent allogeneic HSCT. We analyzed 70 adult patients with a minimum follow-up of 100 days who underwent myeloablative allogeneic HSCT. Thirty patients were identified as having cGVHD and one patient NS without evidence of cGVHD. This patient was a-34-year-old woman. She received unmanipulated blood HSCT for acute myeloid leukemia from her HLA full-matched brother. The conditioning was with busulfan and cyclophosphamide. Cyclosporine and short course methotrexate were given as GVHD prophylaxis. The major early posttransplant complication was severe hemorrhagic cystitis. She did not experience GVHD. After 4 months of GVHD prophylaxis cessation, pedal edema was detected during routine follow-up. The serum albumin level was 1.9 g/dL with urinary protein excretion rate 6 g/day. Creatinine clearance was within normal limits, but serum lipid levels were increased. She was in hematological remission and DNA analysis revealed complete chimerism. Renal biopsy showed normal architecture of the glomerulus with normal thickness of the basement membrane. Immunofluorescence microscopy revealed a characteristic pattern of membraneous nephropathy (MN); thin subepithelial granular deposits of immunoglobulin G and C3 along the glomerular basement membrane. Hydroxy-methylglutaryl coenzyme A reductase inhibitor and angiotensin-converting enzyme inhibitor treatment were initiated to reduce serum lipid levels and urinary protein excretion, respectively. Prednisone was administered as immunosuppressant. The patient de-veloped bilateral avascular necrosis of the femoral head and refused further therapies. Steroid treatment was withdrawn. Eight years after the diagnosis of NS, the disease did not progress. The proteinuria persisted but decreased to 0.5–1.5 g/day and the serum albumin level rose to 2.8 g/dL. She has still denied any symptom signifying an underlying disorder or GVHD. As conclusion, the risk of NS as a postHSCT MN should be considered and renal functions should be carefully monitored. The evolution of NS does not usually parallel in the clinical course of cGVHD (2–4). MN—the most common finding on renal biopsy—may be underrecognized until it is clinically symptomatic (5). In all series reported to date, the clinicopathologic features of NS demonstrated that there is an immune-mediated process (1–6). We consider that there may be an association between cGVHD and postHSCT MN, but the treatment should be individualized, especially in cases without manifestations of cGVHD. Sevgi Kalayoglu-Besisik Department of Internal Medicine Division of Hematology Istanbul University Istanbul School of Medicine Istanbul, Turkey Alper Yurci Department of Internal Medicine Division of Gastroenterology Erciyes University School of Medicine Kayseri, Turkey Halil Yazici Department of Internal Medicine Division of Nephrology Istanbul University Istanbul School of Medicine Istanbul, Turkey Ipek Yonal Department of Internal Medicine Istanbul University Istanbul School of Medicine Istanbul, Turkey Deniz Sargin Department of Internal Medicine Division of Hematology Istanbul University Istanbul School of Medicine Istanbul, Turkey

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.

Familial Chilblain Lupus, a Monogenic Form of Cutaneous Lupus Erythematosus, Maps to Chromosome 3p

Systemic lupus erythematosus is a prototypic autoimmune disease. Apart from rare monogenic deficiencies of complement factors, where lupuslike disease may occur in association with other autoimmune diseases or high susceptibility to bacterial infections, its etiology is multifactorial in nature. Cutaneous findings are a hallmark of the disease and manifest either alone or in association with internal-organ disease. We describe a novel genodermatosis characterized by painful bluish-red inflammatory papular or nodular lesions in acral locations such as fingers, toes, nose, cheeks, and ears. The lesions sometimes appear plaquelike and tend to ulcerate. Manifestation usually begins in early childhood and is precipitated by cold and wet exposure. Apart from arthralgias, there is no evidence for internal-organ disease or an increased susceptibility to infection. Histological findings include a deep inflammatory infiltrate with perivascular distribution and granular deposits of immunoglobulins and complement along the basement membrane. Some affected individuals show antinuclear antibodies or immune complex formation, whereas cryoglobulins or cold agglutinins are absent. Thus, the findings are consistent with chilblain lupus, a rare form of cutaneous lupus erythematosus. Investigation of a large German kindred with 18 affected members suggests a highly penetrant trait with autosomal dominant inheritance. By single-nucleotide-polymorphism-based genomewide linkage analysis, the locus was mapped to chromosome 3p. Haplotype analysis defined the locus to a 13.8-cM interval with a LOD score of 5.04. This is the first description of a monogenic form of cutaneous lupus erythematosus. Identification of the gene responsible for familial chilblain lupus may shed light on the pathogenesis of common forms of connective-tissue disease such as systemic lupus erythematosus.

Outcome and Treatment of Bucillamine-Induced Nephropathy

Background: Bucillamine (BCL), a treatment for rheumatoid arthritis, occasionally causes proteinuria. Renal specimens are reported to show segmental granular deposition of immunoglobulin G, associated with membranous nephropathy. Long-term course and optimal treatment have remained unknown, and were investigated here. Methods: We examined clinical records of 400 patients treated with BCL for rheumatoid arthritis, at our hospital from 1998 to 2003, finding 17 with proteinuria and biopsy-proven BCL-induced nephropathy. Results: In all 17 patients, proteinuria resolved without loss of renal function between 3 and 85 months after discontinuing BCL (14.1 ± 3.4). The only factor influencing time to remission was pathologic stage of membranous nephropathy (stage I vs. stage II or III: 11.5 ± 4.8 vs. 21.6 ± 3.3 months; p = 0.02). Maximal proteinuria, total amount of BCL, BCL exposure time, and use of prednisolone or other immunosuppressant agents did not significantly influence time until remission. Conclusion: The most important therapeutic step in treating BCL-induced nephropathy is to discontinueBCL. Prednisolone or other immunosuppressant agents might not be effective.

Diffuse Dermal Angiomatosis

Two cases of diffuse dermal angiomatosis are reported in middle-aged women. This rare disease of unknown origin is characterized by increased dermal angiomatosis and ulceration. The clinical and histologic presentations of the presently reported lesions were typical for this disorder. Endothelial cells exhibited a normal immunophenotype. The perivascular basement membranes showed a distribution of collagen alpha chains typical for blood vessels, but not for lymphatics. Immunohistochemistry revealed other undescribed features. At the site of the clinical lesions, linear and granular deposits of immunoglobulins A and M, and complement were found around the vessels and at the dermal-epidermal junction. The same deposits were also found restricted to the dermal-epidermal junction in the peripheral clinically intact skin. No serological signs of auto-immune disorder were detected in one patient. A monoclonal gammopathy was disclosed in the other patient. A pattern of immunoreactant deposits similar to that disclosed in the two patients was not found in the control specimens, and has not been described so far in other types of vascular hyperplasia and neoplasia. A pathogenic role of these deposits is unsettled and should be further explored.

Discoid lupus erythematosus presenting as acneiform pitting scars

A 32‐year‐old man presented with conspicuous acneiform pitting scars on the right nasolabial fold of 3 years’ duration (Fig. 1). He stated that the scars were preceded by erythematous plaques. Physical examination also revealed perilesional erythematous infiltration and telangiectasia. Tracing back the history, there was no malar erythema, oral ulcer, or arthralgia. A skin biopsy showed irregular acanthosis, follicular plugging, vacuolar degeneration of the basal cell layer with marked melanin incontinence, and heavy periadnexal mononuclear cell infiltration (Fig. 2a,b). Direct immunofluorescence studies displayed continuous granular deposition of immunoglobulin G (IgG) and C3 along the dermo‐epidermal junction. The hemogram, antinuclear antibody (ANA) test, complement, and urinalysis were within normal limits. Based on the histopathologic findings and a positive lupus band test, a diagnosis of discoid lupus erythematosus (DLE) was made.An atrophic plaque composed of conspicuous acneiform pitting scars with surrounding erythema and telangiectasia on the right nasolabial foldimage(a) Marked follicular plugging and perivascular and periadnexal mononuclear cell infiltrates (hematoxylin and eosin, ×40). (b) Vacuolar degeneration of the basal layer with melanin incontinence (hematoxylin and eosin, ×400)image

Membranous Nephropathy Associated with Donor Lymphocyte Infusion following Allogeneic Bone Marrow Transplantation

Nephrotic syndrome after hematopoietic stem cell transplantation (HSCT) followed by donor lymphocyte infusion (DLI) has never been described. We report the case of a myelodysplastic syndrome (MDS) patient who developed nephrotic syndrome with membranous nephropathy 18 months after allogeneic HSCT and 4 months after DLI. A 50-year-old woman with MDS underwent allogeneic bone marrow transplantation from her HLA-matched brother. MDS relapsed 55 days after transplantation, donor lymphocytes were infused as adoptive immunotherapy, and complete remission was achieved. Four months after the third DLI, the patient developed nephrotic syndrome with proteinuria up to 9 g/day. Renal biopsy revealed granular deposits of immunoglobulin G along the glomerular basement membrane, and subepithelial electron-dense deposits. A diagnosis of membranous nephropathy was made. For maintenance of the immunotherapeutic effect of DLI, minimum doses of immunosuppressive therapy for decreasing proteinuria were administered, and improvement of nephrotic syndrome and persistent complete remission of MDS were achieved.