Shoko Fukamachi

Type of skin eruption is an independent prognostic indicator for adult T-cell leukemia/lymphoma

Cutaneous involvement is seen in ~ 50% of adult T-cell leukemia/lymphoma (ATLL) patients. We investigated the association between skin eruption type and prognosis in 119 ATLL patients. ATLL eruptions were categorized into patch (6.7%), plaque (26.9%), multipapular (19.3%), nodulotumoral (38.7%), erythrodermic (4.2%), and purpuric (4.2%) types. When the T stage of the tumor-node-metastasis-blood (TNMB) classification of mycosis fungoides/Sézary syndrome was applied to ATLL staging, 16.0% were T1, 17.7% T2, 38.7% T3, and 4.2% T4, and the remaining 23.5% were of the multipapular and purpuric types. For the patch type, the mean survival time (median survival time could not be estimated) was 188.4 months. The median survival times (in months) for the remaining types were as follows: plaque, 114.9; multipapular, 17.3; nodulotumoral, 17.3; erythrodermic, 3.0; and purpuric, 4.4. Kaplan-Meier curves of overall survival showed that the erythrodermic type had the poorest prognosis, followed by the nodulotumoral and multipapular types. The patch and plaque types were associated with better survival rates. Multivariate analysis demonstrated that the hazard ratios of the erythrodermic and nodulotumoral types were significantly higher than that of the patch type, and that the eruption type is an independent prognostic factor for ATLL. The overall survival was worse as the T stage became more advanced: the multipapular type and T2 were comparable, and the purpuric type had a significantly poorer prognosis than T1.

Aberrant aquaporin 5 expression in the sweat gland in aquagenic wrinkling of the palms

Aquagenic wrinkling of the palms (AWP) is an uncommon disease characterized by the rapid and transient formation of edematous whitish plaques on the palms on exposure to water. Although this disease is occasionally accompanied by hyperhidrosis, the pathophysiology of AWP remains unknown. Herein we describe a patient with AWP. The location of wrinkling was limited to the areas positive for iodine-starch test after water exposure, which suggests that AWP is etiologically related to hyperhidrosis. Histologic examination revealed hyperplastic and papillated eccrine glandular epithelium with the enlarged diameter of eccrine coils. Immunohistochemically, while aquaporin 5 (AQP5), one of the water channel AQP families, was present exclusively in the dark cells of sweat glands of healthy donors, an aberrant AQP5 staining, extending to the clear cells, was found in the patient with AWP. The hyperplastic glandular epithelium and aberrant AQP5 staining in the patients sweat glands suggest that AWP stems from dysregulation of sweating.

Cholinergic Urticaria: Studies on the Muscarinic Cholinergic Receptor M3 in Anhidrotic and Hypohidrotic Skin

TO THE EDITOR Cholinergic urticaria (CU) is a sweating-associated, syringeal orifice-coincident wheal mediated by acetylcholine. CU is occasionally associated with depressed sweating, as reported under the name of anhidrosis (complete lack of sweating) or hypohidrosis (incomplete lack of sweating) (Itakura et al., 2000). There have been reported 29 patients with CU with anhidrosis and/or hypohidrosis (CUAH) (Kay and Maibach, 1969; Itakura et al., 2000; Yoshida et al., 2009). One hypothesis for the relationship between the wheal formation and the depressed sweating is that the patients are hypersensitive to unknown substance(s) in their sweat and develop wheals in response to sweat leaking from the syringeal ducts to the dermis possibly by obstruction of the ducts (Adachi et al., 1994; Kobayashi et al., 2002). In fact, some patients with common CU exhibit wheals to intradermal injection of the patients’ own diluted sweat as well as acetylcholine and histologically show sweat duct obstruction (Fukunaga et al., 2005). However, none of the reported patients with CUAH were positive to the intradermally injected autologous sweat, suggesting that ‘‘sweat hypersensitivity’’ is not responsible for CUAH. In addition, if sweat hypersensitivity is the mechanism, the anhidrotic area should be the predilection site for wheal, but such an observation has not been reported. The study design was approved by the review board of University of Occupational and Environmental Health. Measurements in this study were performed after informed consent had been obtained. The study was conducted according to the Declaration of Helsinki guidelines. To address its mechanism, we investigated four nonsmoker male CUAH patients, aged 23 (case 1), 24 (case 2), 50 (case 3), and 36 years (case 4). The exercise challenge and iodine–starch assessment for sweat induction (Kobayashi et al., 2002) revealed that the skin surfaces of all patients were divided into the anhidrotic and hypohidrotic areas (Figure 1a). The skin with normal sweating was not seen in any patient. As represented by case 1, the applied iodine–starch was discolored by sweat in the hypohidrotic but not anhidrotic area (Figure 1b, left), and following exercise challenge, the patients developed pinpoint wheals in only the hypohidrotic areas (Figure 1b, right). Intradermal injection of acetylcholine yielded wheal with sweating at only the hypohidrotic areas (Figure 1c). The injection of autologous sweat or serum did not produce wheal in either hypohidrotic or anhidrotic area. Histologically, a periglandular lymphocytic infiltrate was observed around eccrine glands in the anhidrotic but not hypohidrotic area of all patients (Figure 1d). There was no occlusion of sweat ducts. By immunohistochemistry, the infiltrating lymphocytes consisted of a mixture of CD4þ and CD8þ T cells (CD4/CD8 ratio, 1.21; Figure 1e). Skin sections were immunohistochemically stained with anti-cholinergic receptor muscarin 3 (CHRM3) antibody (H-210, 1:50; Santa Cruz Biotechnology, Santa Cruz, CA), which is the most important CHR for sweating

Therapeutic Effectiveness of Various Treatments for Eosinophilic Pustular Folliculitis

Eosinophilic pustular folliculitis is a rare dermatosis. Recently, in addition to oral indomethacin, other treatments have been applied for eosinophilic pustular folliculitis. The aim of this study was to assess the effectiveness of various therapies encompassing conventional to newly applied drugs for eosinophilic pustular folliculitis. Twenty patients with eosinophilic pustular folliculitis seen in our department were investigated. The effectiveness of each treatment was assessed by a severity score index. Eleven patients were treated with oral indomethacin, and the severity scores of all patients were decreased after the treatment. Oral cyclosporine was markedly effective in all 11 patients treated, and topical tacrolimus ointment alleviated eosinophilic pustular folliculitis in 3 of 7 with one patient showing a remarkable reduction in the severity score. In addition to indomethacin or other oral non-steroidal anti-inflammatory drugs, oral cyclosporine and topical tacrolimus may be beneficial choices when patients have been resistant to previous treatments.

D1-like dopamine receptors antagonist inhibits cutaneous immune reactions mediated by Th2 and mast cells

BACKGROUND Dopamine transduces signals via five subtypes of G protein-coupled receptors. Among these subtypes, the D1 and D5 receptors belong to the D1-like group. Although dopamine is known to mediate immune responses, its involvement in cutaneous immunity remains unclear. OBJECTIVE The aim of this study is to determine the role of dopamine and its D1-like receptors in cutaneous immune responses. METHODS By using the D1-like receptor antagonist SCH 23390, we examined the role of D1-like receptors in murine models of Th1-type contact hypersensitivity and Th2-type atopic dermatitis in vivo, and in mast cells and Th2 cell differentiation in vitro. RESULTS Administration of SCH 23390 did not affect Th1-type contact hypersensitivity but suppressed the immediate-type reaction (ITR) and the late phase reaction (LPR) in the atopic dermatitis model. In addition, SCH 23390-treated mice showed higher IFN-γ and lower IL-4 mRNA levels in the ear skin of challenged mice than did non-treated mice as analyzed by real-time RT PCR. Consistently, the passive cutaneous anaphylaxis reaction was significantly reduced in SCH 23390-treated mice. Moreover, dopamine enhanced mast cell degranulation and Th2 cell differentiation, and both activities were abrogated by SCH 23390. CONCLUSION These findings suggest that the D1-like receptors mediate immediate and late phase skin reactions by promoting Th2 induction and mast cell degranulation.

Modulation of semaphorin 3A expression by calcium concentration and histamine in human keratinocytes and fibroblasts

BACKGROUND Both neurotrophins and chemorepellents are involved in the elongation and sprouting of itch-associated C-fibers in the skin. Nerve growth factor (NGF) and semaphorin 3A (Sema3A) are representatives of these two types of axon-guidance factors, respectively. OBJECTIVE We investigated the effects of calcium concentration and histamine on the expression of NGF and Sema3A in normal human epidermal keratinocytes (NHEK) and normal human fibroblasts (NHFb). METHODS NHEK and NHFb were cultured under different calcium concentrations (0.15-0.9 mM) with or without histamine, and the expression of mRNA for NGF and SEMA3A was assessed by real-time PCR analysis. An immunohistochemical study was performed for Sema3A using normal skin and skin cancer specimens. RESULTS In NHEK, SEMA3A expression was elevated by high calcium concentration and reduced by low calcium condition, while NGF expression was not dependent on calcium. Their expressions were unchanged by calcium in NHFb. Immunohistochemically, keratinocytes in the prickle layer of normal epidermis and squamous cell carcinoma cells were positive for Sema3A, sparing basal cells and suprabasal cells. The addition of histamine to NHEK at 10 μg/ml enhanced SEMA3A expression but depressed NGF expression. In NHFb, however, histamine decreased both NGF and SEMA3A levels. CONCLUSIONS Sema3A inhibits C-fiber elongation/sprouting in the upper layers of the epidermis, where calcium concentration is high, thereby determining the nerve endings. Histamine reduces Sema3A production by fibroblasts, allowing C-fibers to elongate in the dermis. In contrast, the histamine-augmented keratinocyte production of Sema3A might suppress C-fiber elongation and exaggerated pruritus.

Valsartan-induced Drug Eruption Followed by CD30+ Pseudolymphomatous Eruption

© 2010 The Authors. doi: 10.2340/00015555-0695 Journal Compilation

Topical Cholecystokinin Depresses Itch-Associated Scratching Behavior in Mice

Cholecystokinin (CCK) serves as a gastrointestinal hormone and also functions as a neuropeptide in the central nervous system (CNS). CCK may be a downregulator in the CNS, as represented by its anti-opioid properties. The existence of CCK in the peripheral nervous system has also been reported. We investigated the suppressive effects of various CCKs on peripheral pruritus in mice. The clipped backs of ICR mice were painted with CCK synthetic peptides and injected intradermally with substance P (SP). The frequency of SP-induced scratching was reduced significantly by topical application of sulfated CCK8 (CCK8S) and CCK7 (CCK7S), but not by nonsulfated CCK8, CCK7, or CCK6. Dermal injection of CCK8S also suppressed the scratching frequency, suggesting that dermal cells as well as epidermal keratinocytes (KCs) are the targets of CCKs. As determined using real-time PCR, mRNA for CCK2R, one of the two types of CCK receptors, was expressed highly in mouse fetal skin-derived mast cells (FSMCs) and moderately in ICR mouse KCs. CCK8S decreased in vitro compound 48/80-promoted degranulation of FSMCs with a transient elevation of the intracellular calcium concentration. These findings suggest that CCK may exert an antipruritic effect via mast cells and that topical CCK may be clinically useful for pruritic skin disorders.

Acute onset disseminated superficial porokeratosis associated with exacerbation of diabetes mellitus due to development of anti-insulin antibodies

The development of disseminated superficial porokeratosis is occasionally observed in association with renal transplant, autoimmune diseases, and various hematological disorders, suggesting a certain immunosuppression may trigger a wide-spread abnormal keratinization. Here we report a case of sudden onset disseminated superficial porokeratosis associated with an exacerbation of diabetes mellitus due to an anti-insulin antibody formation. To our knowledge, this is the first report of disseminated superficial porokeratosis in a patient with severe diabetes mellitus.

Doripenem-induced intertriginous drug eruption as a mild form of AGEP

© 2009 The Authors JEADV 2009, 23, 954–982 Journal compilation