Analysis of IL-10 and IL-35 in dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid.

The association between immunoregulatory cytokines, such as interleukin (IL)-10 or IL-35, and dipeptidyl peptidase-4 inhibitor (DPP4i)-related bullous pemphigoid (BP) has not been evaluated. Serum IL-10 and IL-35 levels were measured in 39 patients with BP (24 males and 15 females; 6 DPP4i-related and 33 DPP4i-unrelated BP patients) and 10 healthy controls. The number of CD26+ cells in the dermis around bulla on sections was counted immunohistochemically for 12 patients (six patients with DPP4i-related BP and six randomly sampled patients with DPP4i-unrelated BP). Patients with DPP4i-related BP had lower levels of serum eosinophils (DPP4i-related vs. DPP4i-unrelated BP: 476.1 ± 234.0 vs. 911.3 ± 948.8/µL; p = 0.537) and a higher rate of infiltrating CD26+ cells (32.9 ± 7.1% vs. 15.7 ± 4.4%; p = 0.01). There were no significant differences in serum IL-10 (6.77 ± 0.24 vs. 6.84 ± 0.20 pg/mL), serum IL-35 (2.63 ± 0.17 vs. 2.63 ± 0.21 pg/mL), serum anti-BP180NC16a antibodies (67.31 ± 37.4 vs. 76.18 ± 54.59 U/mL) and Bullous Pemphigoid Disease Area Index before treatment in this study. Serum IL-10 and IL-35 levels do not increase in patients with BP and may not be a candidate for a therapeutic target for BP. An increase in CD26+ cells might be associated with DPP4i-related BP.

Histological and quantitative polymerase chain reaction-based analysis of Buruli ulcer using mapping biopsy method.

BACKGROUND: In Japan, Buruli ulcer cases are often advanced, requiring surgical treatment. However, extensive debridement is often difficult because of cosmetic and functional sequelae. Moreover, the lesions are complicated and composed of edematous erythema, necrotic ulcer, and erythematous skin lesions caused by a paradoxical reaction, which also make it difficult to perform adequate debridement. METHODOLOGY/PRINCIPAL FINDINGS: We performed quantitative polymerase chain reaction (PCR) analysis for IS2404 using 29 samples taken from mapping biopsy. We evaluated the relationship among mycobacterial burden, histopathological findings, and clinical outcomes using 83 tissue samples taken from mapping biopsy and debrided Buruli ulcer. On quantitative PCR, the Cp values of IS2404 amplification were substantially different in each site. The major histological findings could be divided into massive subcutaneous necrosis with scant inflammatory cell infiltration and dense inflammatory cell infiltration. Of the 84 sites, 34 were subjected to repeated histological evaluations. In these sites, histological necrosis did not disappear over time despite standard antibiotic treatment. In contrast, the ulcers were cured and no recurrences were observed without resecting the 11 biopsied sites that lacked histological necrosis. Although quantitative PCR revealed that a lower Cp value of IS2404 was associated with histological massive necrosis, sites that showed lower Cp values clinically did not always need debridement. CONCLUSION/SIGNIFICANCE: Our descriptive study revealed that the histological findings and amounts of mycobacterial DNA differed according to the sites despite being found in one lesion. Our results showed that the need for surgical debridement in each site was correlated with histological necrosis without inflammatory cell infiltration, as the inflammation is supposed to represent an active host immune response rather than mycobacterial burden. We suggest that the debridement of lesions with histological necrosis in mapping biopsy may be useful for Japanese cases with unsuccessful standard antibiotic treatment to achieve sufficient clinical improvement.

Two cases of annular erythema without bullous lesions by autoimmune blistering diseases.

Although annular erythema is usually observed as one of the cutaneous manifestations of Sjögren's syndrome or subacute cutaneous lupus erythematosus, autoimmune blistering diseases also present with annular erythema. However, bullous lesions are not always found, and there is a rare type without bullous lesions. We present two cases of autoimmune blistering diseases showing annular erythema without bullous lesions. It is important to perform direct or indirect immunofluorescence examination when we encounter multiple annular erythema.

Mutation analysis of IL36RN gene in Japanese patients with palmoplantar pustulosis.

Loss-of-function mutations of the IL36RN gene, encoding interleukin-36 receptor antagonist (IL-36Ra), have been reported as major pathogenic causes of generalized pustular psoriasis (GPP), especially in cases lacking previous histories of psoriasis vulgaris. Palmoplantar pustulosis (PPP), which is traditionally included among GPP-related diseases, has a controversial association with IL36RN. While a negative view about the said association has been recently published from Europe, variations of the IL36RN gene show great ethnic differences. In this study, we performed mutation analysis of the IL36RN gene in 88 Japanese patients with PPP and identified three types of single base substitutions in four patients, namely, p.Pro82Leu in two patients, p.Asn47Ser in one and p.Thr123Met in another. All variations were heterozygous and different from previous European reports. We compared the immunohistochemical findings of IL-36Ra on patients with and without variation of the IL36RN gene; however, no significant differences were observed. Our data and the previous European study suggest that PPP is not associated with mutations of the IL36RN gene.

Anti-signal recognition particle antibody-positive polymyositis in a patient with Sjögren's syndrome showing various types of annular erythema: Positive correlation between the activities of annular erythema and myositis.

Annular erythema with Sjögren's syndrome (AESS) is occasionally found, especially in Asian patients, which is classified into three types. We present a case of Sjögren's syndrome showing various types of AESS with anti-signal recognition particle antibody-positive polymyositis. We successfully treated the eruption and myositis with a low dose of prednisolone. Every onset of annular erythema coincided with elevation of serum creatine kinase levels, which suggests the correlation between the activities of annular erythema and polymyositis.

Increase of interleukin-10-producing B cells associated with long-term remission after i.v. immunoglobulin treatment for pemphigus.

We present a refractory case of pemphigus vulgaris that achieved long-term remission after i.v. immunoglobulin treatment (IVIG). We evaluated the fluctuation of circulating interleukin-10-producing B cells (B10 cells) during the course in our case and other three patients with pemphigus treated with IVIG without clinical remission. B10 cells were observed predominantly in CD1d(-) , CD5(-) , CD9(-) and CD27(+) populations among CD19(+) cells in healthy controls, as well as in patients with pemphigus. The frequency of B10 cells among CD19(+) cells increased in our case, but not in the other three patients without clinical remission, which leads to speculation on the association between the increase of B10 cells and the achievement of long-term remission after IVIG treatment.

Merkel cell carcinoma showing regression after biopsy: Evaluation of programmed cell death 1-positive cells.

We present a cases of Merkel cell carcinoma (MCC) with Merkel cell polyomavirus that showed complete regression after biopsy. The exact mechanism of regression in MCC has remained unclear. It has been reported that apoptosis caused by T-cell immunity was implicated in the regression, and programmed cell death 1 (PD-1), an inhibitory receptor, was expressed in approximately half of tumor-infiltrating T cells in MCC. However, the contribution of PD-1-positive cells for the regression of MCC has not been evaluated. We examined the rate of PD-1-positive cells among the peritumoral mononuclear cells, which showed that the percentage of PD-1-positive cells in the case was significantly lower compared with in MCC without regression. We propose that PD-1-positive cells suppress tumor immunity for MCC, and that reduction of PD-1-positive cells may be associated with tumor regression.

A case of dermatomyositis with esophageal fistula in whom blind mucosal biopsy detected occult oropharyngeal carcinoma.

We present a case of anti-transcription intermediary factor 1 (anti-TIF-1) antibody-positive dermatomyositis with concomitant esophageal fistula and extensive truncal erythema. The characteristic cutaneous features and presence of anti-TIF-1 antibodies were predictive for internal malignancy. However, repeated examinations for internal malignancy showed none, and blind mucosal biopsy was needed to diagnose oropharyngeal carcinoma. We should note the possibility of occult nasopharyngeal carcinoma and consider performing blind mucosal biopsy in dermatomyositis with esophageal fistula, especially with extensive truncal erythema.