Sora Takeuchi

IgM in lesional skin of adults with Henoch-Schönlein purpura is an indication of renal involvement

BACKGROUND Henoch-Schönlein purpura (HSP) is a multisystem disease believed to be a consequence of the entrapment of circulating IgA-containing immune complexes in blood vessel walls throughout the skin, kidneys, and gastrointestinal tract. The skin manifestations are characterized by nonthrombocytopenic palpable purpura over the lower extremities. OBJECTIVE We assessed adult patients with HSP who had nonthrombocytopenic palpable purpura on the extensor surfaces of their lower limbs, and had no associated connective tissue disease. Patient medical records, including clinical presentation, laboratory data, and direct immunofluorescence (DIF) reports, were reviewed retrospectively. METHODS We reviewed the records of 25 adult patients with HSP who presented at our department, between 2006 and 2008, with an initial cutaneous manifestation of palpable purpura on their lower extremities. Adult HSP was defined in all cases as documented leukocytoclastic vasculitis according to a skin biopsy specimen, with histopathologic evidence of IgA deposition by DIF. Statistical analyses were performed using a χ(2) test to compare prevalence among each clinical manifestation. RESULTS There was a significant correlation between IgM deposition by DIF and renal involvement (χ(2) = 5.23, P = .022). IgM deposition and complement 3 deposition by DIF showed a close relationship (χ(2) = 5.11, P = .024). There was a significant positive correlation between serum IgA and C-reactive protein levels (Spearmans rank correlation coefficient = 0.35, P = .044). LIMITATIONS These findings should be validated in larger studies. Renal biopsies were not done to confirm the presence of nephritis. CONCLUSIONS This study suggests that IgM deposition in palpable purpura based on DIF provides an indicator of nephritis in adult patients with HSP. We believe that IgM deposition could be related to the pathogenic factors that trigger the development of renal involvement.

Raised serum levels of interleukins 6 and 8 and antiphospholipid antibodies in an adult patient with Henoch-Schönlein purpura.

The long‐term prognosis of Henoch–Schönlein purpura (HSP) is determined by the severity of renal involvement, known as HSP nephritis, which varies considerably from patient to patient. There is now increasing evidence that dysregulated cytokine production plays a crucial role in human autoimmune and inflammatory processes.

Elevated antilysosomal-associated membrane protein-2 antibody levels in patients with adult Henoch-Schönlein purpura.

Background  Henoch–Schönlein purpura (HSP) is characterized by IgA‐containing immune complexes within leucocytoclastic vasculitis. Lysosomal‐associated membrane protein‐2 (LAMP‐2) was first identified as part of a systematic search for antineutrophil cytoplasmic antibody (ANCA) antigens expressed on neutrophils and endothelial cells.

Significance of two skin biopsy performances with consecutive deeper sections in the differential diagnosis between cutaneous polyarteritis nodosa and livedo vasculopathy.

© 2014 The Authors. doi: 10.2340/00015555-1603 Journal Compilation

Lysosomal-associated membrane protein-2 plays an important role in the pathogenesis of primary cutaneous vasculitis

OBJECTIVES Recent research suggests that lysosomal-associated membrane protein-2 (LAMP-2) could be one of the target antigens in the pathogenesis of vasculitides. We established a transgenic rat model, env-pX rats, with various vasculitides including cutaneous vasculitis. Human primary cutaneous vasculitis includes cutaneous polyarteritis nodosa (CPN) and Henoch-Schönlein purpura (HSP). We measured serum anti-LAMP-2 antibody levels in morbid env-pX rats and injected anti-LAMP-2 antibody into premorbid env-pX rats. We further measured serum anti-LAMP-2 antibody levels in patients with CPN and HSP. METHODS Cutaneous vasculitis was observed in ∼30% of 6-month-old morbid env-pX rats. In contrast, these findings were rare in premorbid env-pX rats under 3 months old. We also examined 85 patients with CPN and 36 adult patients with HSP. Serum anti-LAMP-2 antibody levels were determined using ELISA. Premorbid env-pX rats under 3 months old were given an i.v. injection of anti-LAMP-2 antibody at day 0 and day 7. At day 14, these rats underwent histopathological and direct immunofluorescence examination. Cell surface LAMP-2 expression of rat neutrophils was examined by flow cytometry. RESULTS Serum anti-LAMP-2 antibody levels were significantly higher in morbid env-pX rats than in wild-type normal rats. In addition, the levels in the cutaneous vasculitis group of morbid env-pX rats were significantly higher than the no cutaneous vasculitis group. Intravenous anti-LAMP-2 antibody injection into premorbid env-pX rats under 3 months old induced infiltration of neutrophils into cutaneous small vessels. Anti-LAMP-2 antibody-binding neutrophils were detected there. LAMP-2 expression on the cell surface of neutrophils in premorbid env-pX rats under PMA stimulation was higher compared with controls. Serum anti-LAMP-2 antibody levels in CPN and HSP were significantly higher than those of healthy controls. CONCLUSION These data support a positive relationship between anti-LAMP-2 antibody and cutaneous vasculitis.

Treatment for cutaneous arteritis patients with mononeuritis multiplex and elevated C-reactive protein

Cutaneous arteritis (cutaneous polyarteritis nodosa, CA) is a necrotizing vasculitis of arteries within the skin. CA is a new classification under single‐organ vasculitis, as adopted by the 2012 Chapel Hill consensus conference (CHCC 2012). Some patients originally diagnosed as having CA could develop additional disease manifestations that warrant reclassifying as systemic polyarteritis nodosa (PAN) according to the CHCC 2012. We retrospectively investigated 101 patients with CA seen at our department between 2003 and 2012. There was a significantly higher frequency of inflammatory plaques and leg edema in CA patients with elevated C‐reactive protein (CRP) compared to CA patients with normal CRP. Similarly, there were significant differences in the incidence of arthralgia and mononeuritis multiplex between the two patient groups. We found significantly positive correlations between CRP and creatinine titers in serum in all 101 CA patients. Prednisolone was administrated in a significantly greater percentage of patients with elevated CRP compared to patients with normal CRP. Repeated i.v. cyclophosphamide pulse therapy (IV‐CY) with prednisolone therapy at an early stage resulted in complete resolution without adverse effects or severe complications. We regard inflammatory plaques and leg edema with elevated serum CRP as an indication of a more severe condition, and treated them effectively with prednisolone. Assuming mononeuritis multiplex and/or arthritis exist with elevated CRP, we propose that earlier treatment by IV‐CY with prednisolone should be indicated for CA patients who demonstrate these more severe manifestations to prevent progression to PAN.

Serum levels of interleukin-6 in patients with cutaneous polyarteritis nodosa.

ulcerations. Cutaneous nodules (100.0%) were the most common skin manifestations and were observed in all of our patients with CPN. Forty (88.9%) of the patients with CPN had livedo racemosa, and 33 (73.3%) had purpuric lesions on their lower extremities. Twenty-seven (60.0%) of the patients with CPN were positive for serum CRP, and LAC activity was observed in 27 of them (60.0%). Nineteen (42.2%) of the patients with CPN had elevated serum IL-6 levels and 29 (66.4%) had elevated serum IL-8 levels, while only 4 (8.9%) had elevated serum TNF-α levels. Seven (15.6%) were positive for serum IgG anti-PS/PT antibody, 33 (73.3%) for IgM anti-PS/ PT antibody, and 6 (13.3%) for IgG aCL antibody. DIF studies were performed on skin biopsy samples from 29 of the patients with CPN, and revealed complement 3 expression within affected vessels of the lesions in 21 (72.4%) of them. In addition, 18 (62.1%) of those 29 patients with CPN showed IgM deposition within affected vessels. Thirty-four (75.6%) of the patients with CPN were treated with warfarin, and prednisolone therapy was administered to 27 (60.0%) of them. We divided the 45 patients with CPN into two groups; the elevated IL-6 group and the normal IL-6 group (Table I). The number of men in the elevated IL-6 group was significantly higher than in the normal IL-6 group. Patients with elevated IL-6 had a significantly higher frequency of arthralgia compared with patients without elevated IL-6. Skin ulcerations were also significantly more prevalent among patients with elevated IL-6 compared with patients without elevated IL-6. Elevated IL-6 patients had significantly higher CRP serum levels than normal IL-6 patients. LAC in the elevated IL-6 group was significantly more prevalent than in the normal IL-6 group. Serum IgG anti-PS/PT antibody levels differed significantly between the elevated IL-6 group and the normal IL-6 group. Similarly, serum IgG aCL antibody levels were significantly higher in the elevated IL-6 group compared with the normal IL-6 group. In contrast, IgM anti-PS/PT antibody levels in patients with CPN with elevated IL-6 were significantly lower than in normal IL-6 level patients with CPN. The selected prevalence of prednisolone in the elevated IL-6 group was significantly higher than in the normal IL-6 level group.

Presence of anti-phosphatidylserine-prothrombin complex antibodies and anti-moesin antibodies in patients with polyarteritis nodosa

We measured both serum anti‐phosphatidylserine–prothrombin complex (anti‐PSPT) antibodies and anti‐moesin antibodies, as well as various cytokines (interleukin [IL]‐2, IL‐4, IL‐5, IL‐10, IL‐13, IL‐17, granulocyte macrophage colony‐stimulating factor, γ‐interferon, tumor necrosis factor‐α) levels in polyarteritis nodosa (PAN) patients with cutaneous manifestations. All patients showed the presence of a histological necrotizing vasculitis in the skin specimen. They were treated with i.v. cyclophosphamide pulse therapy (IV‐CY) and prednisolone therapy or steroid pulse therapy. The immunological assessments were performed on sera collected prior to and after treatment with IV‐CY or steroid pulse therapy. We found a significant positive correlation between serum anti‐moesin antibodies and both clinical Birmingham Vasculitis Activity Scores and Vasculitis Damage Index. Anti‐PSPT antibody and IL‐2 levels after treatment in PAN patients were significantly lower than before treatment. In contrast, anti‐moesin antibody levels were higher following IV‐CY or steroid pulse therapy compared with the pretreatment levels. In the treatment‐resistant PAN patients (n = 8), anti‐PSPT antibody levels after treatment were significantly lower than before treatment. In contrast, anti‐moesin antibody levels after treatment in the patients were significantly higher compared with the pretreatment levels. Immunohistochemical staining revealed moesin overexpression in mainly fibrinoid necrosis of the affected arteries in the PAN patients. We suggest that measurement of serum anti‐PSPT antibody levels could serve as a marker for PAN and aid in earlier diagnosis of PAN. We also propose that elevated serum anti‐moesin antibodies could play some role of the exacerbation in patients with PAN.

Novel monoclonal antibodies that recognize both rat and mouse phosphatidylserine/prothrombin complexes.

To the Editor, Anti-phospholipid syndrome (APS) is a prothrombotic disorder characterized by anti-phospholipid antibodies in the serum [1]. Anti-phospholipid antibodies recognize phospholipid-bindi...

Benign Symmetric Lipomatosis Associated with Atopic Dermatitis and Chronic Alcohol Abuse in a Japanese Man

© 2009 The Authors. doi: 10.2340/00015555-0674 Journal Compilation