Search

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.

We examined the prevalence of various cutaneous symptoms including livedo racemosa and inflammatory plaques, lupus anticoagulant (LA), anticardiolipin (aCL) antibodies (Abs), and anti-phosphatidylserine-prothrombin complex (anti-PS/PT) Abs in patients with cutaneous polyarteritis nodosa (PAN) to determine if any of them correlate with the clinical and/or serologic features. If such correlations exist, the clinical and serologic features of the cutaneous manifestations could aid in the early diagnosis and/or treatment of cutaneous PAN. We retrospectively investigated the clinical and serologic features, direct immunofluorescence findings, and treatment methods used in 50 patients with cutaneous PAN seen at our Department of Dermatology between 2003 and 2009. Subcutaneous nodules were observed in all 50 patients, 44 (88.0%) had livedo racemosa, 30 (60.0%) had skin ulcers, and 14 (28.0%) had inflammatory plaques. Levels of serum IgM anti-PS/PT Abs were significantly higher in patients with livedo racemosa than in patients without livedo racemosa. Serum IgG anti-PS/PT Ab levels differed significantly between patients with inflammatory plaques (12.86 ± 13.16 U/mL) and those without inflammatory plaques (6.53 ± 5.92 U/mL). Similar trends were seen with respect to IgG aCL Ab levels. In contrast, levels of IgM anti-PS/PT Abs were significantly lower in patients with inflammatory plaques compared to patients without them. Inflammatory plaques were significantly more prevalent in patients with skin ulcers. Warfarin and prednisolone were selected as the primary therapy at a significantly higher rate in patients with inflammatory plaques and skin ulcers than in patients without them. We suggest that a variety of antiphospholipid Abs could influence the cutaneous patterns of cutaneous PAN. In particular, IgG anti-PS/PT Abs and/or IgG aCL Abs could indicate the presence of inflammatory plaques as a specific cutaneous manifestation of cutaneous PAN.

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 (Spearman's 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., (Copyright © 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Granuloma annulare is characterized by noncaseating dermal granulomas with connective tissue changes. A relationship with hematologic and solid malignancies has been suggested in some cases. We describe a 70-year-old man who had erythematous annular plaques on his elbows, upper extremities, and wrists for a period of 3 months. Histologic examination revealed epithelioid cell granulomas associated with dense atypical lymphocytes in the dermis. Immunohistochemical staining of skin specimens showed a prominent infiltration of CD3+, CD4+, CD5+, and CD25+ cells. Human T-cell leukemia virus type I proviral DNA was detected in the blood and cerebrospinal fluid by Southern blot analysis and polymerase chain reaction assay. The patient was given the diagnosis of adult T-cell leukemia/lymphoma based on the initial cutaneous manifestations. His condition progressed rapidly and led to his death. The granuloma annulare-like skin lesions in our patient could be considered as a peculiar immunologic hypersensitivity reaction of the host against the tumor cells or persistent human T-cell leukemia virus type I viral antigens. Dermatologists should be aware that this skin condition may be an initial manifestation of adult T-cell leukemia/lymphoma.

Background: Blood platelets store sphingosine 1-phosphate (S1P) abundantly and release this bioactive lipid extracellularly. S1P acts as an intercellular mediator through interaction with the endothelial differentiation gene (EDG)/S1P family of G protein-coupled receptors. Of the EDG family S1P receptors, EDG-5 (S1P2) is inhibited in migration induced by S1P. Diabetes impairs numerous aspects of tissue repair. Failure of wound angiogenesis is known to delay diabetic wound healing., Objectives: We examined whether S1P subcutaneous injection could improve the healing of full-thickness skin wounds in healthy and diabetic mice. We further determine if the combined S1P and EDG-5 (S1P2) antagonist injection in diabetic mice could affect wound healing. Finally, we examined the histopathological findings of the wound following S1P injection in diabetic mice., Methods: Eight- to 10-week-old BALA/c mice, diabetic db/db mice and Wister rats were used for the studies. A full-thickness wound was made on the dorsal skin of the healthy and diabetic mice. Either 10 microM or 100 microM of S1P or vehicle control (BSA/PBS) was injected into the wound bed every day. We calculated the wound area after each injection. EDG-5 (S1P2) antagonist (JTE-013) or vehicle (DMSO) was then injected in addition to the S1P around the dorsal wound of diabetic mice and the wound diameter was measured. Wound tissue samples were excised following injection for histopathological examination., Results: Wound area in normal BALA/c mice did not significantly decrease upon S1P injection compared to S1P-untreated controls. S1P injection alone showed significant promotion of wound healing in diabetic mice compared to no S1P treatment. The combination of S1P and EDG-5 (S1P2) receptor antagonist administration induced maximal wound healing in diabetic mice. Histopathological examination revealed that S1P induces neo-vascularization potential in rats and diabetic mice wound., Conclusions: S1P injection in diabetic mice significantly accelerated cutaneous wound healing in the neo-vascularization process. The results demonstrate that S1P affects and sustains all key cellular processes responsible for wound repair and point to a unique potential for this molecule in the therapy of diabetic wounds, particularly as an angiogenic agent in treatment of diabetic wounds.

We have previously shown that frontoparietal scleroderma en coup de sabre, a type of linear scleroderma that affects the face and scalp, follows the lines of Blaschko, but the question whether linear scleroderma that occurs in the limbs follows Blaschko's lines has not been answered. We describe the case of a 4-year-old girl with multiple morphea showing remarkable unilateral systematized distribution and whose linear lesions in the limbs appeared to follow Blaschko's lines. We suggest that linear scleroderma of the limbs, as well as frontoparietal scleroderma, may occur along the lines of Blaschko. Since both the unilateral distribution and the lesions along Blaschko's lines are the patterns created by genetic mosaicism, we suggest that a significant part of linear scleroderma and perhaps a smaller part of multiple morphea could be related to cutaneous mosaicism.