Histological features of localized scleroderma 'en coup de sabre': a study of 16 cases.

BACKGROUND: Early lesions of localized scleroderma are histologically characterized by perivascular lymphocytic infiltrate in the reticular dermis and swollen endothelial cells. However, there have been few information regarding histological features other than these findings in localized scleroderma. OBJECTIVE: Since en coup de sabre (ECDS) is a certain subset of localized scleroderma with a relatively uniform clinical manifestation, we focused on this disease subset and evaluated its histopathological features. METHODS: A total of 16 patients with ECDS were retrospectively evaluated on the basis of clinical and histological findings. RESULTS: Regardless of clinical manifestations, vacuolar degeneration was found in all of the ECDS patients. Importantly, keratinocyte necroses were restricted to early and active ECDS lesions. In early ECDS patients (disease duration of <3 years), moderate to severe perivascular and/or periappendageal lymphocytic infiltrate and vacuolar changes in follicular epithelium were more prominent, whereas epidermal atrophy was less frequently observed, than in late ECDS patients (disease duration of ≥6 years). CONCLUSION: Vacuolar degeneration at the dermoepidermal junction is a common histological feature in ECDS and perivascular and/or periappendageal lymphocytic infiltrate and vacuolar degeneration of follicular epithelium are characteristic especially in early ECDS, further supporting a canonical idea that the elimination of mutated epidermal cells by immune surveillance contributes to tissue damage and resultant fibrosis in localized scleroderma.

Serum levels of ADAM12-S: possible association with the initiation and progression of dermal fibrosis and interstitial lung disease in patients with systemic sclerosis.

BACKGROUND: A disintegrin and metalloprotease (ADAM) 12 is one of the metalloproteinase-type ADAMs and possesses extracellular metalloprotease and cell-binding functions. ADAM12 is expressed in two alternative forms, such as a membrane-anchored form (ADAM12-L) and a short secreted form (ADAM12-S). OBJECTIVE: To investigate the clinical significance of serum ADAM12-S levels in systemic sclerosis (SSc). METHODS: Serum ADAM12-S levels were determined by a specific enzyme-linked immunosorbent assay in 61 SSc patients and 18 healthy controls. RESULTS: Serum ADAM12-S levels were significantly increased in diffuse cutaneous SSc (dcSSc) patients than in healthy controls (0.417 ± 0.389 vs. 0.226 ± 0.065 ng/mL; P < 0.05), while being comparable between limited cutaneous SSc (0.282 ± 0.258 ng/mL) and healthy controls. Serum ADAM12-S levels significantly elevated in dcSSc patients with disease duration of ≤ 6 years (0.537 ± 0.449 ng/mL, P < 0.05), but not in dcSSc with disease duration of >6 years (0.225 ± 0.049 ng/mL), compared to healthy controls. Furthermore, in dcSSc patients with disease duration of ≤ 6 years, serum ADAM12-S levels correlated positively with modified Rodnan total skin thickness score, ground glass score, and serum C-reactive protein values, while showed inverse correlation with fibrosis score. CONCLUSION: Elevated serum ADAM12-S levels are associated with elevated serum inflammatory marker, severity of skin fibrosis, and activity of interstitial lung disease in dcSSc, suggesting the possible contribution of ADAM12-S to the pathological events in this disorder.

Constitutive activation of c-Abl/protein kinase C-δ/Fli1 pathway in dermal fibroblasts derived from patients with localized scleroderma.

BACKGROUND: A noncanonical pathway of transforming growth factor-ß signalling, the c-Abl/protein kinase C-δ (PKC-δ)/Friend leukemia virus integration 1 (Fli1) axis, is a powerful regulator of collagen synthesis in dermal fibroblasts. OBJECTIVES: To investigate the significance of the c-Abl/PKC-δ/Fli1 pathway for the establishment of the profibrotic phenotype in lesional dermal fibroblasts from patients with localized scleroderma (LSc). METHODS: The activation status of the c-Abl/PKC-δ/Fli1 pathway was evaluated by immunoblotting and chromatin immunoprecipitation using cultured dermal fibroblasts from patients with LSc and closely matched healthy controls and by immunostaining on skin sections. The effects of a platelet-derived growth factor receptor inhibitor AG1296 and gene silencing of c-Abl on the expression levels of type I collagen were evaluated by immunoblotting. RESULTS: The phosphorylation levels of Fli1 at threonine 312 were increased, while the total Fli1 levels and the binding of Fli1 to the COL1A2 promoter were decreased, in cultured LSc fibroblasts compared with cultured normal fibroblasts. Furthermore, in cultured LSc fibroblasts, the expression levels of c-Abl were elevated compared with cultured normal fibroblasts and PKC-δ was preferentially localized in the nucleus. These findings were also confirmed in vivo by immunohistochemistry using skin sections. Moreover, gene silencing of c-Abl, but not AG1296, significantly suppressed the expression of type I collagen in cultured LSc fibroblasts. CONCLUSIONS: Constitutive activation of the c-Abl/PKC-δ/Fli1 pathway at least partially contributes to the establishment of the profibrotic phenotype in LSc dermal fibroblasts, which provides a novel molecular basis to explain the efficacy of imatinib against skin sclerosis in a certain subset of LSc.

Augmented production of soluble CD93 in patients with systemic sclerosis and clinical association with severity of skin sclerosis.

BACKGROUND: The cell surface protein CD93, expressed on endothelial and myeloid cells, mediates phagocytosis, inflammation and cell adhesion. A soluble form of CD93 (sCD93) is released during inflammation. OBJECTIVES: To determine the serum sCD93 level and its association with clinical parameters in patients with systemic sclerosis (SSc). METHODS: Serum sCD93 levels were examined by enzyme-linked immunosorbent assay in 59 patients with SSc, 24 patients with systemic lupus erythematosus and 47 healthy individuals. The expression of CD93 in skin tissues was examined immunohistochemically. In a retrospective longitudinal study, sera from 11 patients with SSc were analysed. RESULTS: Serum sCD93 levels were increased in patients with SSc compared with healthy individuals (P<0·001). Patients with diffuse cutaneous SSc showed greater levels of sCD93 than those with limited cutaneous SSc (P<0·01) or systemic lupus erythematosus (P<0·01). Serum sCD93 levels correlated positively with the severity of skin sclerosis. Strong CD93 immunostaining was observed on endothelial cells in lesional skin tissues. In the longitudinal study, sCD93 levels decreased in parallel with improvement in skin sclerosis. CONCLUSIONS: Serum sCD93 levels are increased in patients with SSc and correlate with the severity and activity of skin sclerosis. CD93 may contribute to the development of skin fibrosis in SSc.

CCL13 is a promising diagnostic marker for systemic sclerosis.

BACKGROUND: Previous studies suggest that CCL13 may have some role in the pathogenesis of systemic sclerosis (SSc). OBJECTIVES: To determine serum levels of CCL13 and its clinical associations in patients with SSc. METHODS: Serum CCL13 levels were examined by enzyme-linked immunosorbent assay in 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), 20 patients with dermatomyositis (DM), 29 patients with atopic dermatitis (AD) and 50 healthy individuals. RESULTS: Mean + or - SD serum CCL13 levels were elevated in patients with SSc (81.3 + or - 55.8 pg mL(-1)) compared with healthy controls (15.0 + or - 9.9 pg mL(-1); P < 0.001) and patients with SLE (22.0 + or - 6.9 pg mL(-1); P < 0.001), DM (24.4 + or - 36.1 pg mL(-1); P < 0.001) and AD (18.0 + or - 6.4 pg mL(-1); P < 0.001). Among patients with SSc, there were no differences in serum CCL13 levels between limited cutaneous SSc and diffuse cutaneous SSc. In a longitudinal study, CCL13 levels were generally unchanged during the follow-up. CONCLUSIONS: Serum CCL13 was specifically increased in patients with SSc, but not in patients with SLE, DM or AD or in healthy controls. CCL13 could be a promising serological marker for SSc.

Elevation of IgG levels is a serological indicator for pulmonary fibrosis in systemic sclerosis with anti-topoisomerase I antibodies and those with anticentromere antibody.

It is unclear whether any clinical and laboratory features are associated with pulmonary fibrosis (PF) in systemic sclerosis (SSc). We assessed these features using a database of 29 patients with SSc and anti-topoisomerase I antibodies and 68 patients with SSc and anticentromere antibody (ACA). Clinical features were not associated with the incidence of PF in patients with SSc and anti-topoisomerase I antibodies, although severe skin sclerosis was correlated with the presence of PF in patients with ACA. Serum IgG levels were often raised in patients with SSc and PF. Serum IgG levels in patients with PF were significantly higher than those in patients without PF, and were negatively correlated with percentage vital capacity and percentage diffusing capacity of the lung for carbon monoxide. In addition, serum IgG levels were correlated with serum interleukin-6. Thus, serum IgG levels are associated with PF in patients with SSc and anti-topoisomerase I antibodies and in patients with SSc and ACA.

Blockade of CD40/CD40 ligand interactions attenuates skin fibrosis and autoimmunity in the tight-skin mouse.

OBJECTIVE: To assess the association of CD40/CD40 ligand (CD40L) interactions with the development of skin fibrosis and autoimmunity in tight-skin (TSK/+) mouse, which is a mouse model for human systemic sclerosis. METHODS: Newly born TSK/+ mice were treated with murine anti-CD40L monoclonal antibody (100 microg intraperitoneally weekly). Hypodermal thickness of 8-week-old female mice (defined as the thickness of a subcutaneous loose connective tissue layer beneath the panniculus carnosus) was measured under a light microscope. All skin sections were taken from the para-midline, upper back region. Serum anti-topoisomerase I autoantibody levels, serum immunoglobulin levels and plasma soluble CD40L levels were determined by enzyme-linked immunosorbent assay. For analysis of lymphocyte surface molecules, single cell suspensions of lymphocytes were stained by monoclonal antibodies. Proliferation of TSK/+ B cells and fibroblasts to anti-CD40 antibodies was assessed by the uptake of [3H]-labelled thymidine and bromodeoxyuridine, respectively. RESULTS: The blockade of CD40/CD40L interactions by anti-CD40L monoclonal antibody significantly reduced cutaneous fibrosis (65%) and anti-topoisomerase I autoantibody in TSK/+ mice. Anti-CD40L monoclonal antibody also normalised B lymphocyte abnormal activation in TSK/+ mice, demonstrated by hyper-gamma-globulinaemia. Furthermore, augmented CD40/CD40L interactions in TSK/+ mice were suggested by upregulated expression of CD40L on CD4(+) T cells, elevated plasma soluble CD40L levels. The hyperresponsiveness to CD40 stimulation was also observed in TSK/+ B cells and fibroblasts. CONCLUSIONS: Cutaneous fibrosis and autoimmunity in TSK/+ mice are closely correlated with CD40/CD40L interactions.

Muir-Torre syndrome caused by partial duplication of MSH2 gene by Alu-mediated nonhomologous recombination.

We describe a 54-year-old man with a pedicled tumour on the neck. The surgical specimen revealed a sebaceous carcinoma. He belonged to a cancer-prone family susceptible to gastrointestinal cancer. Systemic evaluation for latent malignancies revealed early-stage colonic adenocarcinoma. These findings were compatible with Muir-Torre syndrome (MTS). Microsatellite instability was detected in the sebaceous carcinoma, suggesting a DNA mismatch repair gene mutation. Moreover, duplication of exon 7 generated a nonsense codon at codon 427 of the MSH2 gene causing truncation of MSH2 protein. Immunohistochemical analysis showed diminished MSH2 protein levels in the sebaceous carcinoma and colonic adenocarcinoma. To date, there have been no reports showing duplication of exon 7 of the MSH2 gene in MTS or hereditary nonpolyposis colorectal cancer kindreds. Furthermore, the present case indicates that the dermatologist plays an important role in the diagnosis of MTS and evaluation for latent malignancies.

Taxane-induced scleroderma.

We report five women who presented with scleroderma due to taxanes, mimicking systemic sclerosis. All five patients had received taxane chemotherapy for the treatment of metastatic breast cancer. Marked oedema began first, followed by skin sclerosis occurring mainly at the distal ends of the extremities 6-12 months after the administration of taxane in all patients. Skin biopsies showed full-layer dermal fibrosis with thickened collagen bundles, and perivascular monocytic cell infiltration. These cases resemble systemic sclerosis in terms of their clinical course and histological findings. However, clinical findings including Raynaud's phenomenon and pulmonary fibrosis as well as immunological abnormalities associated with systemic sclerosis were not detected in any of the patients. Although the mechanisms have not been clarified, it should be noted that taxane is causally involved in the formation of scleroderma-like skin conditions.

Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis: an association with malignancy.

OBJECTIVE: Myositis-specific autoantibodies (MSAs) are a useful tool in diagnosis, defining clinical subsets and predicting prognosis of dermatomyositis (DM) and polymyositis (PM). In this study, we identified a novel MSA reactive with 155 and 140 kDa nuclear proteins [anti-155/140 antibody (Ab)] and determined the clinical feature of DM patients positive for this autoantibody (autoAb). METHODS: Sera from 52 Japanese patients with DM, 9 with PM, 48 with systemic lupus erythematosus (SLE), 126 with systemic sclerosis and 18 with idiopathic interstitial pneumonia were examined by immunoprecipitation assays. Positive sera were further characterized by immunodepletion and immunofluorescence staining. RESULTS: Seven of the 52 (13%) Japanese patients with DM immunoprecipitated 155 and 140 kDa proteins from 35S-labelled K562 leukaemia cell extract. No patients with SLE, systemic sclerosis or idiopathic interstitial pneumonia as well as healthy controls were positive for this autoAb. Patients with anti-155/140 Ab developed heliotrope rash, Gottron's papules or sign and flagellate erythema significantly more frequently than those negative. Notably, internal malignancy was found at significantly higher frequency in those positive than those negative (71 vs 11%; P < 0.005). In contrast, none of these patients positive for this autoAb had interstitial lung disease. CONCLUSIONS: This novel MSA is associated with cancer-associated DM and may serve as a diagnostic serological marker for this specific subset.

A clue for telangiectasis in systemic sclerosis: elevated serum soluble endoglin levels in patients with the limited cutaneous form of the disease.

BACKGROUND: The transforming growth factor-beta (TGF-beta) system plays a critical role both in systemic sclerosis (SSc) and hereditary hemorrhagic telangiectasia (HHT). Endoglin, known as a gene responsible for HHT, is a TGF-beta receptor preferentially expressed on endothelial cells. The role of endoglin in SSc is potentially intriguing since limited cutaneous SSc (lcSSc) and HHT share several symptoms, including telangiectasia. OBJECTIVE: To determine serum levels of soluble endoglin (sEndoglin) and clinical associations in patients with SSc. METHODS: Serum sEndoglin levels were examined by ELISA in 70 patients with SSc, 20 patients with systemic lupus erythematosus and 20 healthy individuals. RESULTS: Serum sEndoglin levels were significantly elevated in patients with lcSSc compared with diffuse cutaneous SSc and systemic lupus erythematosus patients as well as normal controls. Patients with elevated sEndoglin levels had telangiectasia more frequently than those with normal sEndoglin levels. Furthermore, pulmonary artery pressure was positively correlated with sEndoglin levels in patients with lcSSc. CONCLUSION: Abnormal expression/function of endoglin may be linked to lcSSc-specific manifestations.

Regulation of local and metastatic host-mediated anti-tumour mechanisms by L-selectin and intercellular adhesion molecule-1.

Malignant melanoma is often accompanied by a host response of inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the role of adhesion molecules, including L-selectin and intercellular adhesion molecule-1 (ICAM-1), in this process, subcutaneous primary growth and metastasis to the lung of B16 melanoma cells not expressing L-selectin, ICAM-1 or their ligands were examined in mice lacking L-selectin, ICAM-1 or both. Primary subcutaneous growth of B16 melanoma was augmented by loss of L-selectin, ICAM-1 or both, while pulmonary metastasis was enhanced by the loss of L-selectin or combined loss of L-selectin and ICAM-1. In both situations, the combined loss of L-selectin and ICAM-1 exhibited the greatest effect. This enhancement was associated generally with a reduced accumulation of natural killer (NK) cells, CD4+ T cells and CD8+ T cells and also with a diminished release of interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha but not interleukin (IL)-6. Cytotoxicity against melanoma was not defective by the absence of ICAM-1, L-selectin or both, suggesting that the enhancement of tumour growth and metastasis caused by the loss of adhesion molecules results from an impaired migration of effector cells into the tissue rather than from a suppression of the cytotoxic response. The results indicate that L-selectin and ICAM-1 contribute co-operatively to the anti-tumour reaction by regulating lymphocyte infiltration to the tumour.

Serum levels of monocyte chemotactic protein-3/CCL7 are raised in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis.

OBJECTIVE: To determine serum levels of monocyte chemotactic protein-3 (MCP-3) and its clinical associations in patients with systemic sclerosis (SSc). METHODS: Serum MCP-3 levels from 69 patients with SSc were examined by ELISA. RESULTS: Serum MCP-3 levels were raised in patients with SSc (n = 69) compared with healthy controls (n = 28). Patients with diffuse cutaneous SSc (n = 36) had higher levels of serum MCP-3 than those with limited cutaneous SSc (n = 33). Patients with raised MCP-3 levels had pulmonary fibrosis and decreased vital capacity (VC) more often than those with normal MCP-3 levels. MCP-3 levels correlated positively with the extent of skin fibrosis, and inversely with %VC and carbon monoxide transfer factor (Tlco) in patients with SSc. CONCLUSION: MCP-3 levels were increased in patients with SSc, and correlated with the extent of skin sclerosis and the severity of pulmonary fibrosis. These results suggest that MCP-3 may have a role in the development of fibrosis in SSc.

Increased cutaneous T-cell-attracting chemokine levels in sera from patients with systemic sclerosis.

OBJECTIVE: We sought to assess serum cutaneous T-cell-attracting chemokine (CTACK) levels and CTACK expression levels in skin from patients with systemic sclerosis (SSc), and determine whether serum CTACK levels correlate with clinical features in SSc patients. METHODS: Serum samples were obtained from 73 SSc patients, 32 patients with systemic lupus erythematosus and 26 patients with dermatomyositis. Serum CTACK levels were determined by enzyme-linked immunoabsorbent assay. CTACK mRNA expression in sclerotic skin was assessed by real-time reverse transcription-polymerase chain reaction. RESULTS: Serum CTACK levels were significantly increased in patients with diffuse cutaneous SSc (dSSc; n=32) and those with limited cutaneous SSc (lSSc; n=41) compared with normal controls (n=31; P<0.05 and P<0.0005, respectively). The presence of calcinosis and muscle involvement was more frequently detected in SSc patients with elevated CTACK levels (P<0.05 and P<0.05, respectively). Elevated C-reactive protein levels were also observed more frequently in SSc patients with increased CTACK levels (P<0.05). CTACK mRNA expression levels in the sclerotic skin of SSc patients were augmented. In a longitudinal study, serum CTACK levels were generally decreased during the follow-up. CONCLUSIONS: The increased serum CTACK levels and enhanced skin CTACK expression in SSc patients suggest that CTACK is related to the inflammation associated with SSc.

Autoantibodies against phosphatidylserine-prothrombin complex in patients with systemic sclerosis.

OBJECTIVE: To determine the frequency and clinical association of antiphosphatidylserine-prothrombin complex (PS/PT) antibody (Ab) in systemic sclerosis (SSc). METHODS: Anti-PS/PT IgG Ab was examined by enzyme linked immunosorbent assay (ELISA) in 112 patients with SSc. Thirty three healthy volunteers and 30 patients with systemic lupus erythematosus (SLE) were also investigated as controls. RESULTS: Anti-PS/PT Ab was detected in 18/112 (16%) patients with SSc and 10/30 (33%) patients with SLE, whereas it was not detected in any normal controls. Anti-PS/PT Ab was more frequently detected in patients with SSc with peripheral ischaemia and lung disease (pulmonary fibrosis and pulmonary hypertension) than in patients with SSc without the Ab. However, anti-PS/PT Ab was not associated with the severity of skin sclerosis. Importantly, two patients were negative for both lupus anticoagulant and Ab against cardiolipin beta(2)-glycoprotein I complex among six anti-PS/PT Ab positive patients with SSc and a thromboembolic episode. CONCLUSIONS: Anti-PS/PT Ab is associated with thromboembolism, peripheral ischaemia, and lung involvement in some patients with SSc. Examination of this Ab may be useful to recognise the risk of thromboembolism in patients with SSc.

Serum soluble CTLA-4 levels are increased in diffuse cutaneous systemic sclerosis.

OBJECTIVE: To determine serum levels of soluble cytotoxic T-lymphocyte associated molecule-4 (sCTLA-4) and clinical association in patients with systemic sclerosis (SSc). METHODS: Serum sCTLA-4 levels from 32 patients with diffuse cutaneous SSc (dSSc) and 27 patients with limited cutaneous SSc (lSSc) were examined by enzyme-linked immunosorbent assay (ELISA). For a longitudinal study, 211 sera from 30 SSc patients were analysed (follow-up 2.1-7.0 yr). RESULTS: Serum sCTLA-4 levels were elevated in dSSc patients compared with normal controls (n = 41), lSSc patients and patients with active systemic lupus erythematosus (SLE) (n = 23). By contrast, sCTLA-4 levels in patients with lSSc or SLE were normal. SSc patients with elevated sCTLA-4 levels had a shorter disease duration and more frequent presence of digital pitting scars, contracture of phalanges, diffuse pigmentation, pulmonary fibrosis and decreased percentage vital capacity (%VC) than those with normal sCTLA-4 levels. sCTLA-4 levels correlated positively with the extent of skin fibrosis, serum IgG levels and anti-topoisomerase I antibody levels. In a longitudinal study, sCTLA-4 levels decreased on a parallel with improvement of skin sclerosis in five dSSc patients. Skin sclerosis did not improve in two of six dSSc patients with high sCTLA-4 levels throughout the follow-up, while the remaining four patients showed improvement of skin sclerosis. CONCLUSION: These results suggest that sCTLA-4 correlates with disease severity and activity of SSc and that sCTLA-4 plays a role in immunological abnormalities of SSc, since sCTLA-4 may augment humoral immune responses as well as T-cell responses by interfering with B7-CTLA-4 interactions that induce negative signals in T and B cells.

Serum concentrations of soluble P-selectin glycoprotein ligand-1 are increased in patients with systemic sclerosis: association with lower frequency of pulmonary fibrosis.

OBJECTIVE: To determine serum concentrations of soluble P-selectin glycoprotein ligand-1 (sPSGL-1) and its clinical associations in patients with systemic sclerosis. METHODS: Serum sPSGL-1 concentrations from 65 patients with systemic sclerosis were examined by enzyme linked immunosorbent assay. In a retrospective longitudinal study, 177 sera from 35 patients with systemic sclerosis were analysed (follow up 0.3 to 6.3 years) RESULTS: Serum sPSGL-1 was raised in patients with limited cutaneous systemic sclerosis (lSSc) (n = 34) and diffuse cutaneous systemic sclerosis (dSSc) (n = 31) compared with healthy controls (n = 22) and patients with systemic lupus erythematosus (n = 20) or dermatomyositis (n = 20). Patients with systemic sclerosis who had raised sPSGL-1 concentrations less often had pulmonary fibrosis and decreased vital capacity (%VC) than those with normal sPSGL-1 levels. sPSGL-1 concentrations were positively correlated with %VC in patients with systemic sclerosis. In the longitudinal study, patients with systemic sclerosis but without pulmonary fibrosis had consistently increased sPSGL-1 concentrations in the early phase, while those with pulmonary fibrosis had decreased sPSGL-1 throughout the follow up period. CONCLUSIONS: A raised serum sPSGL-1 is associated with a lower frequency and severity of pulmonary fibrosis in systemic sclerosis. sPSGL-1 could be a protective factor against the development of pulmonary fibrosis in this disease and as such would be a possible therapeutic target.

Longitudinal analysis of serum KL-6 levels in patients with systemic sclerosis: association with the activity of pulmonary fibrosis.

OBJECTIVE: To determine whether changes in serum KL-6 levels reflect the activity of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc). METHODS: KL-6 levels were determined by ELISA in 39 SSc patients. In a retrospective longitudinal study, 250 serum samples were analyzed during a follow-up period of 0.3-6.1 years. RESULTS: KL-6 levels at the first visit were higher in patients with SSc, especially with PF, compared with healthy controls. In the longitudinal study, KL-6 levels in 4 patients with anti-topo I Abs increased rapidly, parallel to the progression of PF. Four patients with inactive PF exhibited elevated, but stable levels of KL-6 during the follow-up. The 31 patients with almost normal KL-6 levels during the follow-up exhibited no deterioration or new onset of PF. CONCLUSION: Rapidly increased serum KL-6 levels during disease course were associated with new onset or deterioration of PF.

A case of febrile ulceronecrotic Mucha-Habermann disease requiring debridement of necrotic skin and epidermal autograft.

We report a case of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) in a 21-year-old man. This disease is a severe form of pityriasis lichenoides et varioliformis acuta (PLEVA) and is characterized by the sudden onset of diffuse ulcerations associated with high fever and systemic symptoms. It is sometimes lethal especially in elderly patients. In the present case, intense generalized maculopapular erythematous plaques with central necrosis developed progressively in association with a high fever. Initial treatment with systemic betamethasone had been unsuccessful and the skin lesions, which covered about 50% of the body surface, became severely ulcerated. Although the development of new lesions had ceased spontaneously, widespread ulceration of the skin remained. Debridement of the necrotic skin and skin grafting using cultured epidermal autografts and meshed allografts of cadaver skin led to prompt reepithelization.