Follicular extension of atypical keratinocytes predicts the resistance of actinic keratosis to topical imiquimod treatment: A single-center retrospective analysis.

Topical imiquimod therapy has been widely used for actinic keratosis (AK). However, some cases are refractory to treatment. Therefore, an indicator that can predict its efficacy is desired. Herein, we retrospectively analyzed 52 AK lesions treated with imiquimod to investigate the characteristics of refractory lesions. Imiquimod was applied in a cycle of three times weekly for 4 weeks, followed by a 4-week break. This treatment cycle was repeated up to three times and treatment responses were evaluated. As a result, a complete response (CR) was observed in 78.8% (41/52) of lesions. Next, treatment response of lesions was correlated with clinicopathological characteristics including clinical morphology and thickness, pathological morphology and thickness, and presence of follicular extension (FE). Of these, lesions with FE were significantly less responsive to imiquimod treatment; while 92.6% of AK lesions without FE achieved a CR, only 64.0% of AK lesions with FE achieved a CR (p = 0.029). Logistic regression analysis revealed that FE was the sole significant predictor of its efficacy (p = 0.019). These results suggest that preliminary histological evaluation of FE may be useful to predict the efficacy of imiquimod for AK.

Rituximab therapy for refractory autoimmune bullous diseases: A multicenter, open-label, single-arm, phase 1/2 study on 10 Japanese patients.

This was a multicenter study of rituximab, a chimeric monoclonal immunoglobulin G antibody directed against CD20, for the treatment of refractory autoimmune bullous diseases (pemphigus and pemphigoid). Ten patients (three with pemphigus vulgaris, six with pemphigus foliaceus and one with bullous pemphigoid) were treated with a single cycle of rituximab (four weekly infusions at a dose of 375 mg/m2 of body surface area). The primary end-points were the number of serious adverse events and rate of complete remission at 40 weeks. Five patients (50%) achieved complete remission with minimal therapy (defined as no active lesions with lower doses of systemic corticosteroids compared to that with prednisolone 10 mg/day). Improvements in clinical scores (Pemphigus Disease Area Index) and decreases in autoantibody titers in the sera were observed in the four pemphigus patients who failed to achieve complete remission. This suggests that rituximab was effective in nine of 10 cases. Two serious adverse events (Pneumocystis carinii pneumonia and septic shock due to infectious arthritis) were observed and adequately treated with hospitalization. CD19-positive B lymphocytes in the peripheral blood decreased on day 29 following rituximab treatment, and remained at low levels throughout the observation period (280 days). Our results confirmed the efficacy of rituximab therapy for refractory autoimmune bullous diseases in Japan.

Thymoma-associated multi-organ autoimmunity: A case of graft-versus-host disease-like erythroderma complicated by Good syndrome successfully treated by thymectomy.

Thymoma-associated multi-organ autoimmunity disease (TAMA) is a rare paraneoplastic disorder, clinicopathologically similar to graft-versus-host disease (GVHD). Many reported cases follow a difficult course; half of them die from serious infectious diseases subsequent to immunosuppression induced by chemotherapy for unresectable thymoma, or intensive therapies including systemic steroids for complicating autoimmune diseases and GVHD-like symptoms. We report a patient whose skin symptoms were improved subsequently to total thymectomy. The patient also presented with hypogammaglobulinemia, which led to the diagnosis of complicated Good syndrome. Taking account of her immunodeficient condition, antibiotics and i.v. immunoglobulin were administrated promptly on onset of bacterial pneumonia, which was successfully treated. According to a review of the published work, treatments with systemic steroids for skin symptoms have limited effects and may contribute to serious infection. Our case indicates that successful treatment of thymoma itself may lead to the amelioration of the disease. The management priority should be given to the treatment of thymoma and the control of subsequent immune abnormality other than GVHD-like erythroderma.

Validation of chemiluminescent enzyme immunoassay in detection of autoantibodies in pemphigus and pemphigoid.

BACKGROUND: A novel chemiluminescent enzyme immunoassay (CLEIA) was recently developed to quantify autoantibodies specific for desmogleins (Dsgs) and BP180, the target antigens of pemphigus and pemphigoid. This assay is automated and highly accurate and efficient. OBJECTIVE: To validate the use of the CLEIA for detection of autoantibodies during the clinical courses of patients with pemphigus and pemphigoid. METHODS: To define cut-off values for Dsg1, Dsg3, and BP180, we evaluated 47 serum samples from patients with pemphigus foliaceus (PF), 59 from those with pemphigus vulgaris (PV), 52 from those with bullous pemphigoid (BP), and 995 from healthy individuals. We also evaluated any fluctuations in CLEIA titers according to disease activity during the clinical course of 10 cases each of PF, PV, and BP. We used clinical symptom scores, the pemphigus disease area index (PDAI) and the bullous pemphigoid disease area index (BPDAI), to evaluate disease activity. RESULTS: The cut-off values for the CLEIA titers determined by the Youden index were 15.4U/mL for Dsg1, 14.9U/mL for Dsg3, and 16.8U/mL for BP180. CLEIA titers fluctuated in parallel with the PDAI/BPDAI scores in 28 of the 30 cases with PF, PV, or BP. Although the CLEIA and enzyme-linked immunosorbent assay (ELISA) values in the same samples differed substantially in some cases, the concordance rates of positive/negative results between the CLEIA and ELISA were 96% for Dsg1, 97% for Dsg3, and 96% for BP180. CONCLUSION: The CLEIA, a newly developed, highly effective autoantibody detection system, is as reliable as ELISA for evaluation of the clinical courses of pemphigus and pemphigoid.

Novel and recurrent ATP2A2 mutations in Japanese patients with Darier's disease.

Darier's disease (DD, keratosis follicularis: OMIM#124200) is an autosomal dominant skin disorder characterized by multiple dark brown keratotic plaques and warty papules covered by thick crusts. Most cases of DD are caused by mutations in ATP2A2, which is expressed in both the skin and the brain. ATP2A2 encodes the cardiac muscle SERCA2a protein and the ubiquitously expressed SERCA2b. SERCA2 plays an important role as a calcium pump. It is thought that a mutation in ATP2A2 causes dyskeratosis and abnormality of cell-cell adhesion. Here, we report five DD patients from five independent families who presented or were referred to the Nagoya University Hospital in the past five years. We detected five mutations in ATP2A2, including a previously unreported mutation. We observed no apparent genotype/phenotype correlation between types and sites of the ATP2A2 mutations and DD phenotypes in the present series of DD patients. Genetic diagnosis from ATP2A2 mutation search is useful for the definite diagnosis of DD, although it is difficult to predict the severity and prognosis of skin symptoms from the results of the ATP2A2 mutation analysis in DD patients.

Rheumatoid neutrophilic dermatosis with tense blister formation: a case report and review of the literature.

We report a 78-year-old woman with rheumatoid neutrophilic dermatosis (RND) presenting with tense blisters; an extremely rare manifestation of this condition. Systemic corticosteroid was of limited efficacy, while dapsone was effective. A literature review of four similar cases showed that tense blisters in this type of RND tended to appear on the lower extremities of aged, female rheumatoid arthritis patients. Of note, half of the cases were resistant to corticosteroids, as anti-neutrophil agents are reported to be effective. Accordingly, it is important to recognise this unusual manifestation for the timely initiation of appropriate therapy.

[An adult case of acute cerebellitis after influenza A infection with a cerebellar corical lesion on MRI].

We report an adult case of acute cerebellitis associated with influenza A. A 25-year-old woman with fever and headache was diagnosed as having influenza A infection, because nasal swab extract was found positive in the influenza assay. She was treated with oseltamivir. After the treatment, she gradually developed gait and speech disturbance. Neurological examination revealed dysarthria with scanning slurred speech, and limb and truncal ataxia. Cerebrospinal fluid showed pleocytosis and a four-fold or greater change in the antibody titer to influenza virus A (H3N2) detected by HI. T2-weighted brain MRI demonstrated a high signal lesion in the cerebellar cortex. 123I-IMP-SPECT showed hypoperfusion in the cerebellum. Thus, acute cerebellitis associated with influenza A infection was diagnosed. Her symptoms partially improved after steroid pulse therapy, whereas the cerebellar cortical lesion observed on MRI, truncal ataxia and cerebrospinal fluid pleocytosis remained. The cerebellar cortical lesion observed on MRI disappeared 80 days after hospitalization, and the truncal ataxia and cerebrospinal fluid pleocytosis had normalized about three months later.