Eri Araki

Clustering of Syndecan-4 and Integrin β1 by Laminin α3 Chain–derived Peptide Promotes Keratinocyte Migration

Syndecans function as receptors for extracellular matrix (ECM) with integrins in cell spreading. However, the molecular mechanism of their specific involvement in cell migration or in wound healing has not been elucidated yet. Here, we report that a synthetic peptide, PEP75, which contains the syndecan-binding sequence of the laminin alpha 3LG4 module, induces keratinocyte migration in in vitro and in vivo. Soluble PEP75 induced the clustering of syndecan-4 and conformation-modified integrin beta1 colocalized with syndecan-4 in soluble PEP75-induced clusters. Treatment of cells in solution with PEP75 resulted in the exposure of the P4G11 antibody epitope of integrin beta1 in immunostaining as well as in flow cytometry and augmented integrin beta1-dependent cell adhesion to ECM. Pulldown assays demonstrated that PEP75 bound to syndecan-4, but not to integrin beta1. A siRNA study revealed a role for syndecan-4 in PEP75-induced up-regulation of P4G11 antibody binding and migration of HaCaT cells. We conclude that binding of soluble PEP75 to syndecan-4 induces the coupling of integrin beta1, which is associated with integrin beta1-conformational changes and activation, and leads to keratinocyte migration. To activate integrin function through syndecans could be a novel therapeutic approach for chronic wound.

Relationship between the distribution of pseudoxanthoma elasticum skin and mucous membrane lesions and cardiovascular involvement

Pseudoxanthoma elasticum (PXE) primarily affects organs that are abundant in elastic fibers, such as the skin, eye and blood vessels, and may eventually cause loss of vision or cardiovascular disease (CVD). Because CVD is a potentially life‐threatening complication, its early detection is important for improving the quality of life of PXE patients. To determine the relationship between the distribution of skin and mucous membrane lesions and the prevalence of CVD in patients with PXE, we examined 14 PXE cases who presented between 2004 and 2007. All patients had angioid streaks (AS) and positive pathological findings. The skin lesions in PXE patients are distributed discontinuously and thus the degrees of skin involvement were assessed by determining the presence or absence of PXE skin and mucous membrane lesions in six sites (oral mucosa, neck, periumbilical region, cubital fossa, axillae and inguinal regions). Each site was given a binary score (i.e. present = 1, absent = 0) irrespective of severity and the scores were summed to yield a total distribution score (potential range of 0–6). Four cases had PXE‐associated CVD. Their mean distribution score was 5.7, which was significantly higher than the score of the cases without CVD (1.8) (P = 0.0049). There was also significant correlation between the high distribution score (P = 0.0053) as well as CVD (P = 0.029) with the maximum width of AS. A higher distribution score and the presence of oral mucosal lesions were associated with CVD. This scoring method may be useful for predicting the presence of CVD in PXE patients.

Adult-onset Multiple Eccrine Angiomatous Hamartoma in Enlarging Hairy Plaques

Sir, Eccrine angiomatous hamartoma (EAH) is a rare benign hamartoma of eccrine glands and blood vessels. It most commonly develops before adulthood as a single, slowgrowing lesion on the extremities. We describe here a case of adult-onset EAH with generalized multiple hairy reddish-brown indurated plaques with a rapidly progressive course. As the lesions showed histopathological findings such as an increase in mature eccrine glands and blood vessels, the diagnosis was determined to be EAH. This case was observed carefully because the lesion had characteristics not only of a hamartoma but also of a tumour.

Multiple dermatomal daughter lesions of postzoster granuloma

1 Onodera S, Ukai K, Suzuki Y et al. Changes in the prevalence of HCV infection during 10 years in an HCV epidemic area of Japan. Nippon Rinsho 2004; 62 (Suppl. 7):264–6. 2 Quesada JR, Gutterman JU. Psoriasis and alpha-interferon. Lancet 1986; i:1466–8. 3 Conlon KC, Urba WJ, Smith JW 2nd et al. Exacerbation of symptoms of autoimmune disease in patients receiving alpha-interferon therapy. Cancer 1990; 65:2237–42. 4 Georgetson MJ, Yarze JC, Lalos AT et al. Exacerbation of psoriasis due to interferon-alpha treatment of chronic active hepatitis. Am J Gastroenterol 1993; 88:1756–8. 5 Watashi K, Hijikata M, Hosaka M et al. Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. Hepatology 2003; 38:1282–8. 6 Watashi K, Ishii N, Hijikata M et al. Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. Mol Cell 2005; 19:111–22. 7 Inoue K, Sekiyama K, Yamada M et al. Combined interferon alpha2b and cyclosporin A in the treatment of chronic hepatitis C: controlled trial. J Gastroenterol 2003; 38:567–72. 8 Hayashi J, Nakashima K, Yoshimura E et al. Detection of HCV RNA in subjects with antibody to hepatitis C virus among the general population of Fukuoka, Japan. J Gastroenterol 1994; 29:147–51.

Red‐brown macules on the abdomen

A healthy 63-year-old man presented with progressive impairment of vision. Fundoscopy examination revealed angioid streaks and neovascularization of the retina in the right eye. No visible skin lesions in the neck, axillae, groin and oral mucosa were found. The patient had a 30-year history of a red-brown rash on the upper abdomen, which consisted of small round red-brown macules in a weak reticular arrangement (Fig. 1). There was no history of cardiovascular disease.

Extensive skin necrosis of the arm in a patient with complex regional pain syndrome.

We report a 36‐year‐old woman with complex regional pain syndrome (CRPS) type 1 presenting with extensive skin necrosis of the left arm. The patient cooled her arm with ice packs to ease severe pain due to CRPS, in spite of repeated cautions against frostbite injury. The regions of skin necrosis corresponded with the sites where she had applied ice packs. We considered that the severe skin necrosis in our case was due to a self‐induced frostbite injury.

Case of AIDS disclosed by refractory pruritic xerosis and molluscum contagiosum

Dear Editor, Dermatological problems are known to occur in more than 90% of patients with HIV infection. From opportunistic infections to neoplasms like Kaposi’s sarcoma, a variety of cutaneous abnormalities can be seen throughout the course of HIV infection. Common and nonspecific skin abnormalities, such as seborrheic dermatitis, eczema, pruritic papular eruption, prurigo nodularis, xerosis and pruritus are frequently seen. Unusual clinical presentation of such common cutaneous disorders can sometimes serve as visible indicators of HIV/AIDS. We herein report a patient who developed refractory pruritic xerosis and diffuse molluscum contagiosum (MC) in his adulthood and several years later was diagnosed with AIDS. A 39-year-old Japanese male, who was admitted because of persistent low-grade fever and diarrhea, was referred to us for evaluation of diffuse skin eruptions. The papules first appeared on the face 1.5 years previously and later spread to the whole body. He also had a 3-year history of refractory pruritus on the trunk and extremities. Until then, he had no skin troubles including dry skin or atopic dermatitis. The patient’s past history was remarkable for two episodes of cervical lymphadenopathy and an operation for perianal fistula. On examination, severe xerosis was present on the whole body and scaly itchy erythema was found on the upper limbs (Fig. 1a). Diffuse brownish pigmentation and linear scars due to scratching were noted over the upper limbs and the back (Fig. 1b).

Primary essential cutis verticis gyrata with hyaluronic acid deposition

1 Pérez A, Rütten A, Gold R et al. Circumscribed palmar or plantar hypokeratosis: a distinctive epidermal malformation of the palms and soles. J Am Acad Dermatol 2002; 47:21–7. 2 Resnik KS, DiLeonardo M. Circumscribed palmar hypokeratosis: new observations. Am J Dermatopathol 2006; 28:112–16. 3 Böer A, Falk TM. Circumscribed palmar hypokeratosis induced by papilloma virus type 4. J Am Acad Dermatol 2006; 54:908–9. 4 Obermoser G, Zelger B. ‘Multifocal’ circumscribed palmar hypokeratosis. Malformation or not? J Am Acad Dermatol 2003; 49:1197–8. 5 Urbina F, Misad C, Gonzáles S. Circumscribed palmar hypokeratosis: clinical evolution and ultrastructural study after prolonged treatment with topical calcipotriol. J Eur Acad Dermatol Venereol 2005; 19:491–4.

Linearly distributed atrophic patches: a rare cutaneous manifestation of complex regional pain syndrome

Complex regional pain syndrome (CRPS), a term comprising entities formerly known as reflex sympathetic dystrophy (RSD), causalgia and Sudeck’s atrophy, is a severely painful and progressive disorder that usually develops after trauma. The major symptoms include pain [spontaneous pain, hyperalgesia, allodynia (pain evoked by nonpainful stimulus)], movement disorders, abnormal blood flow, sweating, and skin changes. Although cutaneous findings are an important clinical feature of CRPS, detailed reports on its skin alterations are few. We present a unique case of oval atrophic lesions with a linear distribution, a previously unreported type of skin manifestation in CRPS. A 19-year-old girl was referred to our clinic because of depressed skin lesions on her left arm. She also complained of numbness and cold intolerance in the same limb. Ten years previously, she had accidentally slipped and fallen on her left forearm. Within a year, severe burning pain developed at the injury site. She recollected that the first skin change started on the proximal forearm as an erythematous patch, which later became atrophic and depressed. Over the following 5 years, another patch developed on the lateral side of her upper arm, which subsequently progressed to form a severely depressed oval atrophic lesion. Similar oval patches appeared on the distal forearm and the hand, which later coalesced to form a single linear depressed lesion. The pain gradually became milder but a slight burning sensation and numbness persisted, which were exacerbated by cold stimuli. On examination, an atrophic and depressed linear patch was present over the ulnar side of the left forearm and on the hypothenar eminence, which did not match any dermatome or sensory nerve territory (Fig. 1). In addition, two oval atrophic patches were noticed on the lateral aspect of the left forearm and upper arm. Superficial veins were markedly distended in the forearm lesions (Fig. 1). The affected skin also showed mild telangiectasia. The hair was thinner than in the surrounding uninvolved skin. Neurological examinations revealed paraesthesia, dysaesthesia and mild muscle weakness in the patient’s left forearm. No motor-neurone palsy was found. Routine laboratory tests were normal, with negative results for antinuclear antibodies and for Borrelia burgdorferi IgM and IgG antibodies. A biopsy specimen taken from the forearm lesion revealed massive lamellar degenerative changes in the superficial fat layer (Fig. 2). The epidermis and dermis showed no specific findings. These histopathological changes were indistinguishable from lipoatrophy. We diagnosed this case as CRPS I, according to the criteria of the International Association for the Study of Pain (Table 1). Patients with CRPS present with various skin abnormalities, such as oedema, erythema, papules, atrophy, ulceration, pigmentation and bullae. During the acute Figure 2 A biopsy specimen taken from the forearm lesion shows massive lamellar degenerative changes in the superficial fat layer (haematoxylin and eosin, original magnification ·40). Figure 1 (a) A linear atrophic patch over the left forearm and on the hypothenar eminence; (b) an oval atrophic patch on the lateral aspect of the left upper arm with telangiectasia, loss of hair and shiny appearance (arrowheads).