Kyoko Kanno

Developmental alterations of physical properties and components of neonatal-infantile stratum corneum of upper thighs and diaper-covered buttocks during the 1st year of life.

BACKGROUND Although physical properties of neonatal-infantile stratum corneum (SC) change drastically after birth, precise developmental alterations of specific sites have not been fully elucidated. OBJECTIVE To determine the longitudinal alterations of neonatal-infantile SC functions and components of upper thighs and diaper-covered buttocks during the first year of life. The data were compared with those of adults. METHODS Nineteen full-term neonates and their mothers were subjected to the measurements. Skin hydration, water sorption/retention capacity, TEWL were measured. Superficial SC analyses for NMF, ester binding sebum, and free fatty acids were performed by ATR-FTIR spectrometer. Total amount of ceramides (CERs) and CER subclasses were analyzed by NPLC-ESI-MS. RESULTS SC hydration of neonatal thighs was lower than that of their mothers, which rapidly increased during the 1st month. Skin hydration of neonatal buttocks was similar to that of their mothers. This also rapidly increased during the 1st month. The neonatal TEWL was less than those of their mothers indicating more efficient barrier function at both sites, which significantly increased during the 1st year development. This was mostly correlated decreased in the ω-hydroxy fatty acid-esterified CERs. Superficial ester-binding sebum content of neonates was similar to that of their mothers, which significantly decreased during the measurement; the decrease was more marked on buttocks. Neither NMF nor FFA of the superficial SC showed significant alteration during the 1-year development. CONCLUSION Our results indicate that physical functions and components of neonatal-infantile SC show considerable alterations between diaper-covered buttocks and upper thighs during the 1st year development.

An Adult Case of Kawasaki Disease in a Pregnant Japanese Woman: A Case Report

Kawasaki disease is an acute febrile disease predominantly seen in young children. We report a case of Kawasaki disease in a 32-year-old pregnant woman. She developed a generalized erythematous skin rash accompanied by high fever. Bilateral conjunctival congestion, tender cervical lymphadenopathy, an edematous lower lip and peripheral edema followed by desquamation were observed. She was successfully treated with aspirin and intravenous gammaglobulin (1 g/kg/day). Her course was not complicated by coronary artery aneurysm and she delivered a healthy baby. To the best of our knowledge, this is the first case of Kawasaki disease in a pregnant woman. We suggest that Kawasaki disease should be included in the differential diagnosis of a generalized, erythematous skin rash accompanied by high fever in adults.

Correlation of disease activity and serum level of carcinoembryonic antigen in acquired idiopathic generalized anhidrosis: A case report

Hypohidrosis and anhidrosis are congenital or acquired conditions which are characterized by inadequate sweating. Acquired idiopathic generalized hypohidrosis/anhidrosis (AIGA) includes idiopathic pure sudomotor failure (IPSF), which has the following distinct features: sudden onset in youth, increased serum immunoglobulin E and responds favorably to systemic corticosteroid. No clinical markers reflecting the disease severity or activity have been established. Here, we report a case of AIGA in a Japanese patient successfully treated with repeated methylprednisolone pulse therapy. In this case, serum carcinoembryonic antigen (CEA) levels increased up to 19.8 ng/mL along with aberrant CEA immunoreactivity of eccrine sweat glands. Interestingly, the serum CEA level normalized as sweating improved with repeated methylprednisolone pulse therapy. Therefore, serum CEA level may serve as a useful clinical marker of hypohidrosis or anhidrosis.

Serum carcinoembryonic antigen (CEA) as a clinical marker in acquired idiopathic generalized anhidrosis: a close correlation between serum CEA level and disease activity

Hypohidrosis/anhidrosis are congenital or acquired sweating impairments. Among them, acquired idiopathic generalized anhidrosis/hypohidrosis (AIGA) is the most common, and characterized by favourable response to systemic corticosteroid, however, no clinical markers for disease severity or activity have been developed.

Drug-induced hypersensitivity syndrome due to minocycline complicated by severe myocarditis

A 60‐year‐old woman presented with a 13‐day history of a generalized erythematous rash accompanied by fever, periorbital edema and axillary lymphadenopathy. Prior to the appearance of the rash, the patient had been treated with intermittent courses of oral minocycline for cystitis. The patient was diagnosed with drug‐induced hypersensitivity syndrome (DIHS) due to minocycline. During the admission, infectious endocarditis was suspected and the patient was treated with i.v. gammaglobulin (0.4 g/kg per day). The following day, the patient suffered from systemic deterioration and symptomatic low blood pressure that prompted repeat echocardiography which revealed an ejection fraction of 10%. DIHS‐associated myocarditis was suspected and management with circulation assistance devices and steroid pulse therapy were started, resulting in satisfactory resolution. A rise in titer of human herpesvirus‐6, cytomegalovirus and Herpes simplex virus‐1 antibodies was detected. Although minocycline‐induced myocarditis is rare, this severe drug reaction should be considered with DIHS.

Discoid lupus erythematosus exacerbated by radiation therapy

Epidermal cornified cells are attached to each other with modified desmosomes, namely corneodesmosomes. Changes in corneodesmosome degradation process influence the total thickness of stratum corneum and the surface appearance of the skin. The major extracellular constituents of corneodesmosomes are desmoglein 1, desmocollin 1 and corneodesmosin. The intracellular part of corneodesmosomes is cross-linked into cornified cell envelopes. Corneodesmosomes are degraded from the central surface area of each cell. Peripheral corneodesmosomes retain structural integrity up to the skin surface. A hypothesis where tight junctions in the stratum corneum play a role in this spatial difference in corneodesmosome degradation has recently been proposed. Genetic defects in corneodesmosin and inhibitors for proteases involved in corneodesmosome degradation result in accelerated desquamation and severe barrier impairment, presenting as the inflammatory type of peeling skin syndrome and Netherton syndrome, respectively. Abnormal corneodesmosome degradation is also found in more common skin diseases including ichthyosis vulgaris, atopic dermatitis, psoriasis vulgaris, lichen planus and soap-induced xerosis.

Cutaneous lesions of Kikuchi's disease: evolution of histopathological findings.

We report a 38‐year‐old male patient who presented with cutaneous lesions mimicking widespread discoid lupus erythematosus with high‐grade fever, arthralgia and lymphadenopathy. Additional lymph node and skin biopsies, however, revealed karyorrhectic debris without neutrophils and numerous CD68‐positive cells, a characteristic finding of Kikuchis disease (KD). Comparing skin biopsies on different occasions, we could see different forms of histopathology. The histopathology of skin lesions of KD may vary during the clinical course, which may reflect the stage of the disease.

Elevation of serum carcinoembryonic antigen in a case of cholinergic urticaria with failed detection of hypohidrosis by the conventional starch-iodine test.

Dear Editor, Acquired idiopathic generalized anhidrosis (AIGA) is defined as non-segmental generalized hypohidrosis/anhidrosis without any dermatological or neurological causes except limited dysfunction of the autonomic nervous system only in sweating. Idiopathic pure sudomotor failure (IPSF), the most common subtype, presents distinct features, such as sudden onset in youth, absence of any specific skin lesion and favorable response to systemic corticosteroids including repeated methylprednisolone pulse therapy; dysfunction of acetylcholine transmission can be related to the pathomechanism. Recently, serum carcinoembryonic antigen (CEA) level has been proposed as a marker reflecting the disease activity of AIGA as well as a conventional starch–iodine test. Here, we report a case of cholinergic urticaria (CU), in which serum CEA elevation and lymphocytic infiltration around eccrine sweat glands were observed but the conventional test failed to detect hypohidrosis. A 27-year-old Japanese man serving in the self-defense forces presented with sickness accompanied by a history of decreased sweating and occasional heatstroke for 7 months. In conditions usually inducing sweating, such as bathing and physical exercise, he was aware of the appearance of disseminated miliary-sized wheals on the body with itchy and prickling sensation. Blood test only showed elevated serum CEA level (19.1 ng/mL; normal, < 5.0) but no abnormality in cell counts, biochemistry, thyroid function test, immunoglobulin E and antiSSA/B antibody. No intracranial lesion was found by magnetic resonance imaging. A modified Minor test failed to detect obvious hypohidrosis, or to induce wheals or excessive hyperthermia (Fig. 1). However, histopathology showed moderate lymphocytic infiltration around the secretory portion of eccrine sweat glands, where increased CEA expression was revealed by immunohistochemistry. These findings led to the diagnosis of CU without apparent hypohidrosis detected by the conventional Minor test. Oral olopatadine hydrochloride (10 mg/day)

Serum carcinoembryonic antigen specifically increases among various serum markers of adenocarcinoma in hypohidrosis or conditions related to hypohidrosis

Anhidrosis/hypohidrosis are conditions presenting various level of sweating dysfunction. Among them, acquired idiopathic generalized anhidrosis (AIGA) presents inadequate decrease or loss of sweating without apparent neurological and dermatological symptoms except cholinergic urticaria. Recently, serum level of carcinoembryonic antigen (CEA), one of the most well‐known tumor markers, has been proposed as a clinical marker reflecting activity of AIGA. This study was performed to verify the specificity and independence of serum CEA level from the other serum tumor markers especially related to adenocarcinoma. The expression of various tumor markers in the serum collected from three healthy control subjects, four AIGA cases, and a cholinergic urticaria (CU) case with elevation of serum CEA level and history of hyperthermia was analyzed using a membrane‐based antibody array. In all AIGA and CU cases, the intensity of CEA was significantly increased (7.60–15.9 times compared with that of control), relatively well‐reflecting the serum CEA level, and the mean intensity of CEA was 11.8 times higher than the control subjects (P = 0.0011). On the other hand, the ratio of carbohydrate antigen (CA)125 and CA19‐9 was 1.93 and 0.23 times compared with the mean intensity of the control subjects, respectively, and there was no statistical significance. Immunohistochemistry on 10 AIGA cases showed increased expression of CEA but not CA19‐9 and CA125 in the eccrine sweat glands. In conclusion, the elevation of serum CEA level was independent from the other tumor markers in hypohidrotic condition represented by AIGA.

Novel PSTPIP1 gene mutation in pyoderma gangrenosum, acne and suppurative hidradenitis syndrome

Dear Editor, Pyoderma gangrenosum, acne and suppurative hidradenitis (PASH) syndrome is an autoinflammatory disease first reported by Braun-Falco et al. in 2012. It is distinguished from other autoinflammatory diseases including pyoderma gangrenosum, acne and pyogenic sterile arthritis (PAPA) syndrome. PAPA syndrome is caused by PSTPIP1 mutations which activate inflammasome and result in elevation of interleukin-1b. In PASH syndrome, several mutations have been reported in the genes including NCSTN, NOD2, MEFV and PSTPIP1. We present a 37-year-old Japanese woman who had suffered from severe acne on her back and lower legs and suppurative hidradenitis on her axillae and groin since 18 years of age. She had also had recurrent episodes of pyoderma gangrenosum on her lower legs since 25 years of age. She showed no signs of arthritis. Her mother had suppurative hidradenitis and acne, and her younger sister had severe acne. No symptom was detected in her youngest sister. Recently, ulcerative erythema had become enlarged and multiple inflamed eruptions appeared (Fig. 1a). Skin biopsy specimens from the edge of the ulcer showed dense neutrophilic infiltrations in the dermis and destruction of a hair follicle (Fig. 1b,c). From these clinical features and histopathological findings, a diagnosis of PASH syndrome was made. Detailed examination failed to detect any systemic complications. Blood analysis showed an increased leukocyte count of 10 190/lL with 74% neutrophils, an elevated inflammatory marker; other markers were C-reactive protein (6.51 mg/dL), serum immunoglobulin (Ig)G (1906.7 mg/dL; normal, 607–1621) and IgA (381.2 mg/dL; normal, 71–365). There was no monoclonality in serum electrophoresis. Antinuclear antibodies and rheumatoid factor were negative. The patient underwent treatment with oral prednisolone (0.5 mg/kg per day) and the lesions were improved. However, pulmonary thrombosis occurred and was treated with warfarin potassium. To avoid