Rieko Kabashima

Increased circulating Th17 frequencies and serum IL-22 levels in patients with acute generalized exanthematous pustulosis.

Background/Objective  Acute generalized exanthematous pustulosis (AGEP) is a diffuse pustular disorder that usually begins in intertriginous folds with widespread erythema. The causes in the majority of the cases are drugs. T cells and interleukin (IL)‐8 play roles in the development of AGEP, but the mechanism remains to be elucidated. We investigated the involvement of Th17 cells and their cytokine IL‐22 in the pathogenesis.

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

Ectopic extramammary Paget's disease: case report and literature review.

Extramammary Pagets disease that occurs in non-apocrine-bearing regions is referred to as ectopic and has been rarely reported. A 62-year-old man presented with a slowly progressive, asymptomatic light-brown plaque on his back. Histopathological examination revealed the presence of large pale cells with prominent nuclei, which proliferated diffusely and focally in the epidermis. Immuno-histochemically the tumour cells were positive for CK7, GCDFP-15, CEA, and p63. Based on these findings, we diagnosed the tumour as ectopic extramammary Pagets disease. We reviewed the English and Japanese literature and found 29 previously reported cases of ectopic extramammary Pagets disease, including our case, with a predominance of occurrence in the Asian population. The germinative milk line is known to be a possible site where extramammary Pagets disease occurs. Like-wise, some germinative apocrine-differentiating cells might exist on the trunk preferentially in Asians. Attention should be paid to the development of ectopic as well as triple or quadruple EMPD in Asians.

CD30-positive T-cell pseudolymphoma induced by amlodipine.

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Connexin 26 (GJB2) mutations in keratitis-ichthyosis-deafness syndrome presenting with squamous cell carcinoma.

Dear Editor, We report a 58-year-old Japanese woman with keratitis–ichthyosis– deafness (KID) syndrome (Online Mendelian Inheritance in Man: 148210). The patient had been provisionally diagnosed as having ectodermal dysplasia since childhood. She had also suffered from keratitis since 30 years of age. Her twin sister had the same skin conditions. She had a 4-year history of a tumor on the scalp. Physical examination disclosed a sessile, erosive tumor on her scalp (Fig. 1a,b). She had alopecia, sparse eyebrows, and dry and scaly face (Fig. 1a). Another small tumor was present on the right upper eyelid (Fig. 1c). There was hyperkeratosis on the palms (Fig. 1d) and soles (Fig. 1e) and nail dystrophy (Fig. 1f). Audiometry revealed bilateral sensorineural deafness (data not shown). The surgically removed scalp and eyelid tumors showed the presence of invading epithelial lobules, consisting of atypical epithelial cells with squamoid eddies (Fig. 1g). The eyelid tumor had virtually the same histological findings (Fig. 1h). A biopsy specimen taken from the palm showed orthokeratotic hyperkeratosis of the cornified layer (Fig. 1i). After the operation, subcutaneous induration was noticed in her left breast. By mammography, echography and computed tomography, a 17 mm · 15 mm tumor was histopathologically as invasive scirrhous ductal carcinoma of the breast (T1cN1M0, stage IIA). She received a course of chemotherapy (epirubicin, cyclophosphamide and 5-fluorouracil) and is currently on follow up. There was no metastasis or relapse of squamous cell carcinoma (SCC) in our case. Although our patient had no follicular occlusion triad with hidradenitis suppurativa, acne conglobate and dissecting cellulitis of the scalp, a long-term follow up will be needed in this respect. Furthermore, we analyzed connexin-26 (CX26) (National Center for Biotechnology Information: NM_004004), the responsible mutated gene for KID syndrome. After informed consent, genomic DNA was extracted from the patient’s lesional skin. The CX26 exon 2 (819 bp) was amplified via polymerase chain reaction (PCR) and sequencing analysis was performed using a primer pair (CX26 F, 5¢-AgAgCAAACCgCCCAgAgT-3¢, and CX26 R, 5¢-gggAAATgCTAg CgACTgAg-3¢). We identified three heterozygous missense mutations (Fig. 1j): (i) c.79G>A mutation (valinefiisoleucine, V27I); (ii) c.148G > A mutation (aspartic acidfiasparagine, D50N); and (iii) c.341A > G mutation (glutamic acidfiglycine, E114G). Two healthy volunteers had none of these mutations, although one healthy subject possessed a homozygous V27I mutation. The patient was diagnosed with KID syndrome based on the well-characterized D50N mutation. V27I and E114G missense mutations have been identified in patients with non-syndromic hearing loss (NSHL). However, V27I is the most frequent type of polymorphic mutation, suggesting that V27I is not related to pathogenesis in this patient. In immunohistochemical study of the plantar skin, keratinocytes of the prickle to granular layers were strongly stained for CX26 in a normal subject (Fig. 1k), and the staining intensity of those cells in our patient was weaker (Fig. 1l). In the scalp SCC lesion of a non-KID syndrome patient, the neoplastic cells were weakly positive for CX26 (Fig. 1m), but the SCC cells in our patient were negative for CX26 (Fig. 1n), suggesting that D50N and E114G mutations induced a low expression or a conformational change of CX26. However, CX26 expression of breast cancer cells in our patient was positive (Fig. 1o), suggesting that its expression depends on the epithelial cells. To our knowledge, there have been 12 cases of KID syndrome reported with SCC (Table 1). It is possible that epidermal keratinocytes with CX26 dysfunction are prone to transform to neoplastic cells, or the skin losing CX26 function provides a circumstance where SCC easily grows. Especially, the D50N mutation may induce the SCC. Mutations other than D50N have been reported in several Table 1. Reported cases of KID syndrome with SCC

Circulating Th17 cell fluctuation in psoriatic patients treated with topical calcipotriol and betamethasone butyrate propionate.

References 1 Cui J, Shen LY, Wang GC. Role of hair follicles in the repigmentation of vitiligo. J Invest Dermatol 1991; 97: 410–416. 2 Kim CY, Yoon TJ, Kim TH. Epidermal grafting after chemical epilation in the treatment of vitiligo. Dermatol Surg 2001; 27: 855–856. 3 Laxmisha C, Kumari R, Thappa DM. Surgical repigmentation of leukotrichia in localized vitiligo. Dermatol Surg 2006; 32: 981–982. 4 Commo S, Gaillard O, Bernard BA. Human hair greying is linked to a specific depletion of hair follicle melanocytes affecting both the bulb and the outer root sheath. Br J Dermatol 2004; 150: 435–443. 5 Anbar TS, Abdel-Raouf H, Awad SS et al. The hair follicle melanocytes in vitiligo in relation to disease duration. J Eur Acad Dermatol Venereol 2009; 23: 934–939. 6 Tobin DJ, Swanson NN, Pittelkow MR et al. Melanocytes are not absent in lesional skin of long duration vitiligo. J Pathol 2000; 191: 407–416. 7 Moretti S, Spallanzani A, Amato L et al. New insights into the pathogenesis of vitiligo: imbalance of epidermal cytokines at sites of lesions. Pigment Cell Res 2002; 15: 87–92.

Epidermolysis Bullosa Acquisita Associated with Psoriasis

Journal Compilation

Kimura’s disease presenting with a giant suspensory tumor and associated with membranoproliferative glomerulonephritis

Kimuras disease is a rare chronic inflammatory disease, which typically occurs in middle-aged Asian men. This benign lymphoproliferative disorder with tissue eosinophilia is clinically characterized by painless subcutaneous swelling or induration, affecting the head and neck region. Here we present a 42-year-old Japanese woman with a giant tumor on the right inguinal region. The tumor was diagnosed as Kimuras disease, because of massive infiltration of lymphoid follicle-forming lymphocytes and eosinophils with elevated serum immunoglobulin E and blood eosinophilia. She also had nephrotic syndrome histopathologically diagnosed as membranoproliferative glomerulonephritis (MPGN). Renal involvement is known as one of the associated conditions with Kimuras disease. The skin and renal diseases were successfully treated with corticosteroids and surgical removal of the mass.

Scabies superimposed on skin lesions of adult T-cell leukemia/lymphoma: case report and literature review

Scabies is a contagious skin disease caused by Sarcoptes scabiei . Crusted scabies is seen most commonly in patients with immunodeficient diseases, such as acquired immune deficiency syndrome (AIDS). It has been suggested that the balance between the Th1 and Th2 immune responses may influence the outcome of a scabies infestation in a sensitized host, 4 although the precise underlying mechanism remains unknown. Here we report a patient with ATLL whose eruption was infected with scabies mites. Our review of the literature disclosed that ATLL skin lesions provide a circumstance on which scabies is easily superimposed.