Kenichi Isoda

Persistent Release of IL-1s from Skin Is Associated with Systemic Cardio-Vascular Disease, Emaciation and Systemic Amyloidosis: The Potential of Anti-IL-1 Therapy for Systemic Inflammatory Diseases

The skin is an immune organ that contains innate and acquired immune systems and thus is able to respond to exogenous stimuli producing large amount of proinflammatory cytokines including IL-1 and IL-1 family members. The role of the epidermal IL-1 is not limited to initiation of local inflammatory responses, but also to induction of systemic inflammation. However, association of persistent release of IL-1 family members from severe skin inflammatory diseases such as psoriasis, epidermolysis bullosa, atopic dermatitis, blistering diseases and desmoglein-1 deficiency syndrome with diseases in systemic organs have not been so far assessed. Here, we showed the occurrence of severe systemic cardiovascular diseases and metabolic abnormalities including aberrant vascular wall remodeling with aortic stenosis, cardiomegaly, impaired limb and tail circulation, fatty tissue loss and systemic amyloid deposition in multiple organs with liver and kidney dysfunction in mouse models with severe dermatitis caused by persistent release of IL-1s from the skin. These morbid conditions were ameliorated by simultaneous administration of anti-IL-1α and IL-1β antibodies. These findings may explain the morbid association of arteriosclerosis, heart involvement, amyloidosis and cachexia in severe systemic skin diseases and systemic autoinflammatory diseases, and support the value of anti-IL-1 therapy for systemic inflammatory diseases.

Cytokeratin and filaggrin expression in nevus comedonicus.

Abstract:  To elucidate the pathogenesis of abnormal keratinization in nevus comedonicus, we performed an immunohistochemical study using antikeratin and antifilaggrin (filament‐aggregating protein) antibodies. There were no significant differences between nevus comedonicus and normal skin in cytokeratin expression. Although filaggrin was only detected in the granular layer in open comedones, filaggrin was detected in both superficial cells and also intermediate cells in closed comedones, suggesting that filaggrin is involved in the formation of closed comedones. The disorder of terminal differentiation related to filaggrin may play a role in the pathogenesis of abnormal keratinization in nevus comedonicus.

Rare case of disseminated cysticercosis and taeniasis in a Japanese traveler after returning from India.

We report disseminated cysticercosis concurrent with taeniasis in a 31-year-old male Japanese, who had visited India three times and stayed for 1 month each time during the previous 1 year. The patient presented increasing numbers of subcutaneous nodules and expelled proglottids, although numerous cysts were also found in the brain in imaging findings, though no neurological symptoms were observed. Histopathological and serological findings strongly indicated cysticercosis. We found taeniid eggs in his stool by microscopic examination and revealed them as the Indian haplotype of Taenia solium by mitochondrial DNA analysis. We concluded that disseminated cysticercosis was caused by the secondary autoinfection with eggs released from the tapeworm carrier himself. After confirming the absence of adult worms in the intestine by copro-polymerase chain reaction, the patient was successfully treated with albendazole at a dose of 15 mg/kg/day for 28 days. Subcutaneous and intracranial lesions had completely disappeared by the end of the treatment period.

Neuro-Sweet disease: report of the first autopsy case

Background: Neuro-Sweet disease is a rare condition of central nervous involvement accompanied by cutaneous Sweet lesions. Neuropathological changes in neuro-Sweet disease are unknown. Objective: To describe post-mortem findings of the first case of neuro-Sweet disease. Results: A 44-year-old Japanese man developed recurrent episodes of cerebral and brainstem encephalitis with cutaneous Sweet lesions from the age of 34 years. His HLA typing was B54 and Cw1, and the symptoms and MRI abnormalities markedly subsided following corticosteroid therapy. Histologically, there were multiple lesions of perivascular cuffing of small venules by macrophages without vasculitis in the thalamus, temporal lobe, basal ganglia, pons, leptomeninges or ventricular ependym. Conclusions: The core neuropathological findings were: perivascular cuffing around particularly small veins; absence of granulomatous or necrotic angitis; mainly macrophage infiltration; and the thalamus being most affected. In the present case, the diagnosis of neuro-Sweet disease was made by skin biopsy 5 years after the onset of the central neuron system symptoms. We should pay more attention to skin lesions in steroid responsive recurrent encephalitis in patients who are HLA-B54 or Cw1 positive.

Novel acoustic evaluation system for scratching behavior in itching dermatitis: Rapid and accurate analysis for nocturnal scratching of atopic dermatitis patients

Quantitative analysis of itching in patients with itching dermatitis including atopic dermatitis (AD) is indispensable for the evaluation of disease activity and response to therapy. However, the objective evaluation system for itching is limited. We have developed a new objective and quantitative scratching behavior detection system using a wristwatch‐type sound detector. The scratch sound detected on the wrist is recorded on a personal computer through a filtering, squaring and smoothing process by specific hardware. Subsequently, the data is automatically processed and judged for the scratching movement using specific software based on the periodicity and energy of the signal. Twenty‐four measurements for healthy volunteers and those with AD by this system were evaluated by comparison with a simultaneously recorded video analysis system. The ratio of scratching time in sleeping time evaluated by these two systems was almost identical. The healthy subjects scratched their skin approximately 2 min during 6 h of sleeping time, while the mean scratching time of AD subjects was 24 min in their sleeping time. In contrast to the time‐consuming video analysis system, this system takes only several minutes for evaluation of an overnight record. This scratch sound detection system is expected to serve as a new objective evaluation tool for itching dermatitis, namely, AD, and development of anti‐itch therapies for dermatitis.

Keratin and filaggrin expression in keratoacanthoma

To clarify the histogenesis of keratoacanthoma, we studied keratin (K) expression in keratoacanthoma (KA) using 10 different anti‐keratin antibodies against K1, K7, K8, K10, K14, K15, K16, K17, K18 and K19 and anti‐filaggrin (filament aggregating protein) antibody. In the centre of KA, K1 and K10 expressions were declined, and K14 and K16 were detected in the tumour cells, suggesting differentiation towards the outer root sheath beneath the orifice of the sebaceous duct. These results suggest that KA differentiates towards the outer root sheath beneath the opening of the sebaceous duct.

Drug Eruption Caused by Azathioprine: Value of Using the Drug‐Induced Lymphocytes Stimulation Test for Diagnosis

Azathioprine (AZA) is an immunosuppressant commonly used for organ transplantation and autoimmune diseases. Allergic side effects of AZA are rare, and reported allergic skin eruptions from AZA are very limited in Japan. We report AZA‐induced drug eruption that developed in two cases of systemic scleroderma with polymyositis. One case presented with Stevens‐Johnson syndrome, and the other had systemic papular erythema. The stimulation indices of the drug‐induced lymphocyte stimulation test (DLST) for AZA in these two patients were as high as 2,180% and 430%, respectively, but those of healthy volunteers were under 120% without nonspecific suppression of lymphocyte proliferation. Other drugs used simultaneously were ruled out by patch and challenge tests. The challenge test for Stevens‐Johnson syndrome type drug allergy is very risky. DLST is a good diagnostic tool for AZA allergy, especially for severe drug allergy cases.

Efficacy of the combined use of a facial cleanser and moisturizers for the care of mild acne patients with sensitive skin

Acne is a common skin disease that involves the seborrheic area of the face and results from the obstruction of hair follicles followed by inflammation. Careful face washing helps to improve and prevent acne; however, intensive washing has a risk of inducing skin barrier impairment and dry skin, especially in sensitive skin. We hypothesized that skin care combining mild skin cleansing and intensive moisturizing (“combination skin care”) may be effective in the care of acne in subjects with dry skin and/or sensitive skin. We developed a combination skin care with a weakly acidic foaming facial skin cleanser based on a mild detergent, an aqueous lotion with eucalyptus extract and a moisturizing gel containing pseudo‐ceramide and eucalyptus extract. To optimize an ideal facial skin care system for mild acne on sensitive skin, we performed a 4‐week clinical trial with 29 post‐adolescent Japanese women with mild acne with dry and sensitive skin. The acne significantly decreased after this trial accompanied by the improvement of dry skin, a significantly increased endogenous ceramide level in the stratum corneum and an elongated alkyl chain length of the non‐hydroxy acyl sphingosine type ceramide. No adverse events due to the test samples were observed. Based on diagnosis by a dermatologist, 97% of the subjects found the combination skin care to be “useful” or “slightly useful”. Based on these findings, the combined use of a facial skin cleanser and moisturizers is safe and effective for the care of acne in post‐adolescent Japanese women with sensitive skin.

Pilonidal sinus of the supra-auricle area

JEADV 2007, 21, 247–289

Relapse of Dermatomyositis after 10 Years in Remission Following Curative Surgical Treatment of Lung Cancer

A 55‐year‐old woman with dermatomyositis and small cell lung cancer was successfully treated with surgery followed by combination chemotherapy in 1987. She had been in remission without further immunosuppressive therapy for 10 years. However, myositis with cutaneous manifestations specific for dermatomyositis relapsed when the patient was 69 years old. Intensive examinations revealed no neoplasm, and she responded to a moderate dose of systemic corticosteroids. This case suggests a long‐lasting autoimmune abnormality in dermatomyositis and that a neoplasm is an important factor in eliciting an occult dermatomyositis.