Twelve‐week,multicenter, placebo‐controlled,randomized, double‐blind,parallel‐group,comparative phase II/III study of benzoyl peroxide gel in patients with acne vulgaris: A secondary publication

A placebo‐controlled, randomized, double‐blind, parallel‐group, comparative, multicenter study was conducted to investigate the efficacy and safety of benzoyl peroxide (BPO) gel, administrated once daily for 12 weeks to Japanese patients with acne vulgaris. Efficacy was evaluated by counting all inflammatory and non‐inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. All 609 subjects were randomly assigned to receive the study products (2.5% and 5% BPO and placebo), and 607 subjects were included in the full analysis set, 544 in the per protocol set and 609 in the safety analyses. The median rates of reduction from baseline to the last evaluation of the inflammatory lesion counts, the primary end‐point, in the 2.5% and 5% BPO groups were 72.7% and 75.0%, respectively, and were significantly higher than that in the placebo group (41.7%). No deaths or other serious adverse events were observed. The incidences of adverse events in the 2.5% and 5% BPO groups were 56.4% and 58.8%, respectively; a higher incidence than in the placebo group, but there was no obvious difference between the 2.5% and 5% BPO groups. All adverse events were mild or moderate in severity. Most adverse events did not lead to study product discontinuation. The results suggested that both 2.5% and 5% BPO are useful for the treatment of acne vulgaris.     

Indolent,waxing and waning cutaneous presentation of HTLV‐1‐associated adult T‐cell leukemia/lymphoma in an HIV‐1‐positive patient

We present an unusual case of human T‐cell leukemia‐lymphoma virus type 1 (HTLV‐1)‐associated adult T‐cell leukemia/lymphoma in an human immunodeficiency virus (HIV) patient who presented with non‐diffuse, papular, waxing and waning cutaneous eruptions. The patient is a 61‐year‐old Haitian male with history of HIV on highly active antiretroviral therapy (HAART) who presented with multiple painful pink papules on his distal fingers and back for more than a year with a waxing and waning course. Skin biopsy demonstrated a CD4+, CD25+, CD8? lymphocytic proliferation with a clonal T‐cell receptor gene rearrangement. Peripheral blood demonstrated lymphocytosis with a CD4:CD8 ratio greater than 20:1 and an identical T‐cell receptor (TCR) clone as that in the biopsy. HTLV‐1 antibodies and PCR testing for HTLV virus were positive. Retrospective review of CBCs during the past 8 years demonstrated chronic lymphocytosis with a sharp increase in absolute CD4 counts corresponding to the onset of rash. The patient lacked systemic symptoms after 6 months follow‐up.     

Human T‐lymphotropic virus 1 (HTLV‐1)‐associated lichenoid dermatitis induced by CD8+ T cells in HTLV‐1 carrier,HTLV‐1‐associated myelopathy/tropical spastic paraparesis and adult T‐cell leukemia/lymphoma

Human T‐lymphotropic virus type 1 (HTLV‐1) induces adult T‐cell leukemia/lymphoma (ATLL), HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) and carrier. ATLL is a mature CD4⁺CD25⁺CCR4⁺ T‐cell neoplasm, and approximately half of patients have direct skin involvement manifesting patch, plaque, tumor, multiple papules, erythroderma and purpura. However, there exist secondary eruptions without tumor cell infiltration in patients with ATLL or HAM/TSP and carriers of HTLV‐1. To clarify the presence of reactive skin eruptions in HTLV‐1‐infected individuals, we reviewed our patients with HTLV‐1‐associated diseases. In 2002–2012, we saw 50 ATLL or HAM/TSP patients and HTLV‐1 carriers presenting with skin lesions. We retrospectively selected cases that histologically showed lichenoid tissue reactions with predominant infiltration of CD8⁺ T cells, but not CD4⁺ tumor cells. The cases included erythroderma (HTLV‐1 carrier), lichen planus (HTLV‐1 carrier), alopecia areata (HAM/TSP), chronic actinic dermatitis (HTLV‐1 carrier to acute ATLL conversion) and discoid lupus erythematosus (smoldering ATLL). They were graft‐versus‐host disease‐like, major secondary lesions and seen in HTLV‐1 carriers and patients with HAM/TSP and smoldering ATLL. We coin the term HTLV‐1‐associated lichenoid dermatitis (HALD) to encompass the conditions. HALD may occur in association with the elevated immunity toward HTLV‐1‐infected CD4⁺ T cells, thus sharing the pathogenetic role of cytotoxic T cells with HAM/TSP.     

Long‐term outcome of patients with polymyositis/ dermatomyositis and anti‐PM‐Scl antibody

Background To date, no series has analysed long‐term outcome in patients with polymyositis/dermatomyositis (PM/DM) with anti‐PM‐Scl antibody. Objectives The aims of the present study were: (i) to assess clinical features and long‐term outcome, including organ complications, functional course and mortality rate, in patients with isolated PM/DM with anti‐PM‐Scl antibody; and (ii) to evaluate prevalence, characteristics and long‐term outcome of interstitial lung disease (ILD) in patients with isolated PM/DM with anti‐PM‐Scl antibody. Methods The medical records of 20 consecutive patients with isolated PM/DM with anti‐PM‐Scl antibody were reviewed. Results Two patients (10%) achieved remission of PM/DM, whereas 14 (70%) improved and four (20%) had a worsened clinical status. Short‐term recurrences (during tapering of therapy) occurred in nine patients and long‐term recurrences (after discontinuation of therapy) in three patients. Moreover, patients with PM/DM with anti‐PM‐Scl antibody exhibited severe complications, as follows: oesophageal involvement (n = 4) requiring enteral feeding in three cases, ventilatory insufficiency (n = 3) requiring mechanical ventilation in two cases; three other patients had cancer. Interestingly, patients with PM/DM with anti‐PM‐Scl antibody often presented symptoms that are usually found in antisynthetase syndrome, i.e. hyperkeratotic rhagadiform hand symptoms (n = 2; 10%), Raynaud’s phenomenon (n = 8; 40%), arthralgia/arthritis (n = 7; 35%) and ILD (n = 12; 60%). In our cohort, the associated ILD often required combined therapy of steroids and immunosuppressive agents. Conclusions Our series suggests that the presence of anti‐PM‐Scl antibody is not a good prognostic factor in patients with PM/DM, as there appears to be an association with lung and oesophageal involvement; in addition, anti‐PM‐Scl antibody may coexist with malignancy in patients with PM/DM. Furthermore, anti‐PM‐Scl antibody‐positive patients with PM/DM often exhibit ‘mechanic’s hands’, Raynaud’s phenomenon and joint involvement. Our latter findings raise the possibility that the immunogenetic background influences the autoantibody status of these patients; HLA‐DR3 has, in fact, been found in association with antisynthetase syndrome antibodies and with anti‐PM‐Scl antibodies.     

Association of Piebaldism,Multiple Café‐au‐lait Macules,and Intertriginous Freckling: Clinical Evidence of a Common Pathway between KIT and Sprouty‐Related,Ena/Vasodilator‐Stimulated Phosphoprotein Homology‐1 Domain Containing Protein 1 (SPRED1)

Abstract: Piebaldism is a rare genodermatosis caused by KIT mutations. We report the case of a 5‐year‐old boy who had the white forelock and leukoderma of piebaldism, but the presence of many café‐au‐lait macules and axillary and inguinal freckling complicated the diagnosis. Patients with similar cutaneous findings have been previously reported, and their disorder has been attributed to an overlap of piebaldism and neurofibromatosis type 1. Legius syndrome is a recently described syndrome caused by Sprouty‐related, Ena/vasodilator‐stimulated phosphoprotein homology‐1 domain containing protein 1 (SPRED1) mutations that also has multiple café‐au‐lait macules and intertriginous freckling. Based on our current understanding of KIT and SPRED1 protein interactions, we propose that café‐au‐lait macules and freckling may be seen in some patients with piebaldism and does not necessarily represent coexistence of neurofibromatosis type 1.