Alpha-hydroxy acids (AHAs) are carboxylic acids characterized by a hydroxy group on the α carbon atom of the molecules. The constituents of AHAs include glycolic acid, lactic acid, malic acid and tartaric acid. The profound effect of AHAs on disorders of keratinization was first to report by Van Scott and Yu in 1974. Recently, medium concentrations of AHAs have been used in the chemical peeling of photo-aged skin, acne and some skin disorders in Japan. However, the overall knowledge of the pharmacological actions of AHAs on the human skin remains insufficient. I herein briefly reviewed our data and the most recently reported information. The principal action of lower concentrations (5-12%) of AHAs, when applied topically to human skin, is based on an accelerated detachment of corneocytes. The pharmacological effects of a medium concentration (15-30%) of AHAs are a thickening of epidermis, a decreased number of atypia in basal cells, an increase in the amount of acid mucopolysaccharides in the papillary dermis, and an increased expression of factor XIII a transglutaminase in the dermal dendrocytes associated with an increased level of mast cell degranulation. Ultrastructurally, AHAs-treated photo-aged skin samples show a decreased number of desmosomes and thus results in an accumulation of tonofilaments and opening of intercellular spaces of kerationocytes, while no appreciable changes are observed in the melanocytes. In vitro studies revealed that AHAs could induce an increased degree of fibroblast proliferation and collagen production, while they may also suppress tyrosinase activity in human melanoma cell line. Recently, AHAs are becoming one of the unique rejuvenating agents in Japan. Dermatologists have to establish more effective and safer protocols in order to widely use AHAs and also further verify the action mechanisms of AHAs, utilizing image, biochemical and molecular biological analyses.

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A 44-year-old female patient showed a large circinate non-tender erythematous soft plaque on her left forearm without fever or neutrophilia. Her tuberculin reaction was strongly positive and the erythema persisted more than 2 weeks. The lesion was first mistaken for lupus vulgaris, but the histological features were consistent with Sweet’s syndrome and no evidence of lupus vulgaris was found. The strong tuberculin reaction and the fact that an enlargement of the lesion was recognized at the biopsy site were considered to indicate hypersensitivity which is characteristic of Sweet’s syndrome. The patient was diagnosed to have neutrophilic erythema. In 1975, Shino and Nakamizo suggested the term “neutrophilic erythema” for a spectrum of skin lesions that contained not only Sweet’s syndrome but also its subtype, which consisted of either a single lesion or a few lesions, manifested itself on the face or the other regions, often showed recurrence and sometimes lacked any signs of fever or leukocytosis. The eruptions of this subtype showed the same clinical appearance, histological features and a good response to corticosteroids as those of Sweet’s syndrome. I propose that the term “neutrophilic erythema” should therefore be used to describe the subtype of Sweet’s syndrome with minimal constitutional symptoms.

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We report a case of systemic sclerosis complicated with antiphospholipid syndrome in a 50-year-old woman. She showed multiple signs and symptoms such as sclerodactylia, a mask-like face, poikiloderma, multiple skin ulcers, interstitial pneumonia, sick sinus syndrome, and esophageal dysfunction. Both antinuclear antibody and lupus anticoagulant were positive. Initially we diagnosed her with systemic sclerosis. We treated the patient with prednisolone at a dose of 20-40 mg/day, and added steroid pulse therapy three times. Unfortunately, the patient died of pulmonary thromboembolism. We finally diagnosed her to have antiphospholipid antibody syndrome.

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We report four cases of bullous pemphigoid (BP) who had problems with oral corticosteroid therapy but were successfully treated with tetracycline and niacinamide. The first case was a 70-year-old woman with generalized BP. Oral prednisolone 30 mg daily could control the skin lesions, but tapering the corticosteroid treatment proved to be difficult. Additional combination therapy with oral tetracycline 1000 mg and niacinamide 1500 mg daily was able to control the disease. The second case was a 99-year-old woman with moderate BP. Oral betamethasone 1.5 mg daily was effective, but delirium due to the corticosteroid administration appeared. Additional therapy with oral tetracycline 1000 mg and oral niacinamide 600 mg daily enabled a reduction in the corticateroid dosage thus resulting in a significant improvement in the delirium symptoms. The third case was a 91-year-old woman with moderate BP. Initially, therapy with oral prednisolone 30 mg daily was effective and the dosage gradually decreased. Fifteen months later, she had a recurrence of BP and the dosage of prednisolone was thus increased up to 30 mg daily. Thereafter she developed bleeding from the stomach, followed by disseminated intravascular coagulation (DIC). DIC was successfully treated with gavexate. One month later BP recurred but the blisters disappeared after theratment with oral tetracycline and niacinamide. The fourth case was a 75-year-old woman with mild BP. Since she had a previous history of cerebral infarction, we treated her disease with oral tetracycline and niacinamide. The blisters disappeared after two weeks of therapy. These observations suggest that combination therapy of tetracycline and niacinamide is effective against mild to moderate-type BP. Furthermore, the addition of tetracycline and niacinamide may thus make it possible to reduce the oral corticosteroid dosage in the treatment of severe BP.

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A 54-year-old man with Buerger’s disease visited our clinic with an intractable digital ulcer on his right toe which had lasted for 5 years. Povidone-iodine was positive for a patch test on his first visit and thus was replaced by chlorhexidine digluconate. Hyperbaric oxygenation, nicotine-dermal patch and prostaglandin I₂ were all thereafter administered with no improvement. Chlorhexidine digluconate turned out to be a contact allergen as well as povidoneiodine by another patch test. The withdrawal of these disinfectants finally resulted in the dramatic amelioration.

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A 72-year-old man developed keratotic plaques with erythema on the palms and soles, which were resistant to topical steroid therapy. A skin biopsy revealed no specific findings in the specimen on the right palm. Chest computer tomography revealed a mass with spiculation in S₁₀ of the lower right lobe. A transbronchial lung biopsy showed adenocarcinoma. An excision of the cancer lesion and metastasis of the lymph nodes resulted in a gradual decrease in all keratotic plaques; no plaques and erythemas were observed 6 months after the operation. A high level of CEA which had originally been observed decreased to a normal level when the keratotic plaques disappeared.

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A 31-year-old woman who had been suffering from generalized pustular psoriasis (GPP) for 15 years and had been treated with intermittent low dose cyclosporine-A (Cy-A) became pregnant. Pustular eruptions was successfully controlled with 2-4 mg/kg daily dose of Cy-A in the first and the second trimesters of her pregnancy, however, the patient become febrile with widespread pustular eruptions during the third trimester. These symptoms could not be relieved with either high dose Cy-A (5.5 mg/kg daily) or a combination of oral prednisolone (40 mg daily) and Cy-A (4 mg/kg daily). Because the patient’s general condition deteriorated, her baby was delivered at 31 weeks by an elective caesarean section. The infant was a healthy female who weighed 1672 g. After delivery, therapy was switched to etretinate 50 mg daily and thereafter the patient’s symptoms rapidly disappeared. Although the infant was initially monitored in a neonatal intensive care unit for a month, she developed normally thereafter. Cy-A can be used for the treatment of GPP during pregnancy, if carefully monitored by a team of dermatologists and obstetricians, with an acceptable risk of teratogenicity and intrauterine growth retardation for the fetus.

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A case of a 2-year-old boy who demonstrated the discharge of congenital prepubic sinus pus is reported. Magnetic resonance imaging revealed a mass which showed the same signal intensity pattern as a muscle in the subcutaneous level of the median lower abdominal wall. In the operative findings, the sinus ended blindly at the inferior border of the pubic bone. The histological findings of the specimens revealed that the sinus like structure was lined with a squamous epithelium near the surface, while it was lined with a transitional epithelium in the deeper areas.

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A 47-year-old female who complained of a sensorimotor disturbance in her lower extremities and urinary disturbance presented. She first noted a loss of sensation in both feet at 23 years of age, immediately after the birth of her child and thereafter suffered from foot ulcers. She also noted a loss of micturition desire, and urinary incontinence appeared at 42 years of age. She presented with deep cone-shaped ulcers on the pressure-bearing areas of her soles, and she also had a dimple at the midline of her lower back. A neurological examination revealed that a segmental sensorimotor disturbance at the level of the 5th lumbar ∼ 1st sacral segment. MRI demonstrated a tethered cord and lumbosacral lipoma. This case was diagnosed to be mal perfirans pedis due to tethered cord syndrome. The findings of a review of the literature on foot ulcers associated with tethered cord syndrome are also discussed.

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Acquired acrodermatitis enteropathica in a 7-month-old male infant. The patient was the first-born child, with a full term birth, a 3220 g birth weight, and who was breast fed. Erosion and erythema developed in the gluteal regions tarting from around 3 months after birth. Thereafter, erythema developed on the head and face as well. Sparse hair growth was found in some parts of the occipital region and diarrheal symptoms were also noted. At the first medical examination, the serum zinc level was low at 13 μg/dl. The serum zinc level of his mother was normal at 113 μg/dl. The zinc level of the mother’s breast milk was low at 37 μg/dl. Therefore, the child was diagnosed to have acrodermatitis enteropathica due to a low zinc level in the breast milk. Zinc sulfate powder 50 mg was thus administrered daily. As a result, the cutaneous symptoms improved within 2 weeks, and the erythema disappeared completely within 10 weeks.

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A 73-year-old man, who was exposed to atomic bomb radiation when he was eighteen years old, presented our hospital with diffuse erythema over his trunk and extremities. He has been suffering from itching for a few years. His family physician noticed anemia eight months previously. Laboratory examinations revealed increased serum levels of muscle enzymes, indicating LDH 1753 IU/l, GOT 54 IU/l, CK 2348 IU/l (CK-MM 92.3%), aldolase 14.9 IU/l. Btterfly erythema, Gottron’s papules and muscular weakness were not observed. As skin biopsy specimen showed mucin throughout the entire dermis. No liquefaction degeneration at the dermal-epidermal junction existed. A further examination revealed thyroid dysfunction, TSH 53.99 μIU/ml, free T₄ less than 0.4 ng/dl and free T₃ less than 1.0 pg/ml. ECG showed low voltage and a flattened T-wave, and a small quantity of cardiac effusion was observed by cardiac echography. The administration of thyroid hormones improved these symptoms and others, including hearing impairment, coarse hair and a slowness of movement and a speech, which he had not previously been aware of. The most important disorders in hypothyroidism are cutaneous, cardiac, psychiatric and muscular symptoms. Myopathy sometimes develops as the main or the only symptom in patients with hypothyroidism. In our case, highly increased serum levels of muscle enzymes were the most noticeable symptom leading us to suspect dermatomyositis.

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We report the case of a 57-year-old woman who presented with cylindroma and multiple trichoepithelioma. She had an elastic hard nodule on her parietal region measuring 10 mm in diameter. Furthermore, she had multiple papules on the center of her face. A histopathological analysis of both tumors showed the typical findings of cylindroma and trichoepithelioma. The origin of cylindroma remains controversial because of the great variety in the histochemical, enzyme-histochemical and immunohistochemical findings. We think that this rare tumor develops from pluripotential cells and also shows differentiation to the eccrine or apocrine glands.

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A 37-year-old female case with clear cell syringoma is reported. Clear cell syringoma, an unusual type of syringoma, shows a clinical appearance which is closely similar to that of common type syringoma, but is histopathologically characterized by tumor nests of clear cells. Clear cell syringoma is known to be frequently associated with diabetes mellitus. In the Japanese literature, we found 41 cases of clear cell syringoma. Among the 35 cases found to have diabetes mellitus, 28 cases showed either overt diabetes mellitus or an abnormal glucose intolerance.

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We report two caces of granular cell tumor (cases 1 and 2). Case 1 was a 41-year-old man, who presented with a verrucous nodule on his arm. Case 2 was a 74-year-old woman, who presented with nodules and erythema on her trunk. The histopathological features of both cases showed the typical features of granular cell tumors. However, case 1 showed an additional histopathological finding of pseudoepitheliomatous hyperplasia, whereas case 2 lacked this finding. We thus investigated the clinicopathological differences between granular cell tumors associated with the pseudoepitheliomatous hyperplasia and granular cell tumors without this finding by reviewing the Japanese literature including our cases.

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A case of apocrine adenocarcinoma arising in the axilla is reported. A 36-year-old male presented with a reddish firm mass in his right axilla. A biopsy suggested adenocarcinoma. A whole body CT, Ga scintigram and other examinations revealed right axillary lymph node metastasis. An extended skin excision with axillary lymph node dissection and post-operative chemotherapy, using 5-FU and CDDP, were thus performed.

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A 69-year-old woman presented with a subcutaneous painful cyst in the sacrococcygeal region. The resected cyst contained several rice bodies. The wall was yellowish and smooth, and had many protruding structures into the cavity. Histopathologic examination revealed fibrin deposits on the wall covered with several layers of synovial cells, and also thick connective tissues. These histological findings were compatible with bursitis. About one month later, the lesion recurred and was almost identical to its original state, along with the cavity due to the previous operation. At the time of the second operation, the cyst wall was found to be connected with the sacrococcygeal junction where a narrow space existed and a joint-like structure was observed. After a resection of the cyst together with coccygeal bone and joint-like structure, no recurrence has been observed for the past 10 months. The recurrent lesion is thus considered to probably be associated with the joint-like structure in the sacrococcygeal junction.

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We report a case of semispecific myiasis caused by a blowfly bite, Phaenicia sericata, which resulted in the development of infected ulcers due to elephantiasis nostras and which infected both legs of a 65-year-old man. More than two months before undergoing the medical examination, the man noticed insect larvae crawling on his legs but he did not remove them. Both the man and his wife lacked knowledge of illnesses and proper hygiene and had little contact with people outside their family. Furthermore, the patient was found to be diabetic.

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The serum level of soluble interleukin-2 receptor (sIL-2R) is a good marker for T cell activity in vivo and is also considered to reflect the severity of various T cell-related diseases. In atopic dermatitis, T cells play an important role in the development of cutaneous inflammation. In order to elucidate whether sIL-2R is a good marker for atopic dermatitis, we analyzed the correlation between the clinical severity and several laboratory markers including the white blood cell count, the percentage of eosinophils, the eosinophil count, LDH, slL-2R and IgE. Severity most closely correlated with the LDH levels in AD patients over 6 years of age (rs=0.639). The sIL-2R levels also correlated well with severity (rs=0.516). The changes in the sIL-2R levels between remission and aggravation of the disease also correlated with the severity and was also closely equal to the change in LDH (rs=0.827, 0.825). sIL-2R was not specific for AD, since the levels of patients with psoriasis and chronic eczema, especially those in erythroderma, were markedly high. There was a negative correlation between sIL-2R and age in patients below the age of 60. IgE did not correlate with the severity of AD. Therefore, sIL-2R is not specific for atopic patients, however, the sIL-2R level can be useful as a marker for establishing the clinical severity of the disease.

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The temporomandibular joints (TMJ) of 62 patients with systemic sclerosis (SSc) were examined by plain X-ray in the tightly closed or wide-open positions. A disturbance in mouth opening (DMO), defined as having the ability to open the mouth no more than 40 mm, was determined by measuring the range of joint movement. Of the 62 patients, 24 (38.7%) manifested DMO. There was a significant correlation between DMO and diffuse type SSc, complications with Hashimoto disease, and being anti-Topoisomerase 1 antibody positive. Pitting scars tended to co-exist with DMO and in these cases, there was a significantly higher total skin thickness score as well as evidence of long-term disease, and high plasma endothelin and serum thrombomodulin levels. Plain X-ray films effectively visualized mandibular condylar deformity and enabled the range of TMJ movement to be measured in patients with SSc. Therefore, this imaging modality appears to be useful in evaluating the severity of SSc.

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The first choice of treatment for perianal Paget’s disease is a resection. However it is important to clarify whether or not the anorectal function is preserved after surgical treatment. We report three cases of perianal Paget’s disease. Case 1: A 66-year-old male patient had an erythematous plaque with direct invasion into the anal canal. Case 2: A 78-year-old male patient had an erythematous plaque with direct invasion over the dentate line. Case 3: A 55-year-old male patient had an erythematous plaque and a tumor on the rectum mucosa. Histologically, all cases were diagnosed to be Paget’s disease, and the tumor on the rectum mucosa of case 3 was also found to be adenocarcinoma. We performed abdominoperineal resections and a colostomy for cases 2 and 3, which accompanied lesions in rectum beyond the dentate line. For case 1, however, we excised the lesion together with the anal mucosa up to 2 cm from the dentate line, thus preserving the anosphincter muscle. The mucosal defect was covered by pulling down the rectal mucosa. After the operations, no patiants demonstrated any recurrence. We thus consider that cases with perianal Paget’s disease, that dose not invade beyond the dentate line, can be treated, while still preserving the anorectal function.

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[in Japanese]

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[in Japanese]

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