During the past decade, molecular biological techniques have led to the discovery of the molecular basis of many genetic disorders of the skin. In addition, the sequencing of the genome was completed, and protein-coading regions were identified last year. This paper reviews the relationship between modern molecular biology and dermatology and focuses on single gene disorders, polygenic disorders, modifier genes, mosaicism, genotype-phenotype relationships, single nucleotide polymorphisms, DNA chip techniques, microarray techniques, and gene therapy. Molecular biological techniques will play increasingly important roles in clinical dermatology.
Among 74 patients with cutaneous malignant melanoma who visited our clinic between November 1995 and May 2001, 12 (16.2%) had subungual melanoma. Six of these patients had advanced melanoma (Clark’s Level IV or V), and the other 6 had thin melanoma (Clark’s Level I or II). In 4 patients with advanced melanoma, the determination of 5-S-CD levels in gauze exudates using the touch fluorescence method and fine needle aspiration fluorescence method were useful for the definite diagnosis. All 10 patients with acral lentiginous melanoma type had periungual pigmentation, designated Hutchinson’s signs and was observed mainly in the tip of digits. The fundamental pattern of this sign on dermoscopy is a parallel ridge pattern. In addition, diffuse multicomponent pigmentation and black globules/dots were observed in the patients with advanced melanoma. The changes of nail plate in the patients with thin melanoma included melanonychia striata and total melanonychia in 3 and partially destroyed nail and pigmentation under the nail plate in the other 3. Even in the patients without melanonychia striata, histopathological observation revealed the lentiginous proliferation of amelanotic atypical melanocytes in the basal layer of the nail matrix. Bar-code-like linear pigmentation in the hyponychium of the tip of the digits was observed in 5 children with total melanoychia. It was easy to differentiate Hutchinson’s sign of subungual melanoma from pseudo-Hutchinson’s sign of total melanonychia in childfood when using dermoscopy.
Acne is thought to be aggravated by psychological stress. Stress increases the corticotropin-releasing hormone (CRH) level and activates the hypothalamic-pituitary axis. We conducted CRH testing to investigate the hypothalamic-pituitary function in 13 postadolescent female acne patients and compared the results to those obtained from to eight healthy female volunteers. In the acne patients, CRH testing revealed no abnormalities of the serum cortisol (F) or dehydroepiandrosterone (DHEA) baseline, peak, or variation range levels, but the area under the curve (AUC) for DHEA was lower than normal. Baseline serum adrenocorticotropic hormone (ACTH) levels and the AUC for ACTH were significantly higher in the acne patients than in the healthy volunteers, although without a significant difference in the peaks or ranges of fluctuation. In three out of 13 acne patients, an elevated ACTH response to CRH was found. However, there was no correlation with the baseline dehydroepiandrosterone sulfate (DHEA-S) levels or the baseline, peak, variation ranges in the ACTH level, or the AUC for ACTH in the acne patients. These results suggest that some Japanese female acne patients without any signs of masculinism may have a mild abnormality of hypothalamic-pituitary function and that this may be responsible for the aggravation of psychological stress-induced acne.
The patient was a 48-year-old female. She had had Raynaud’s phenomenon since 1986. In 1988, she developed edematous sclerosis of the hands and trismus, and she diagnosed with systemic sclerosis (SSc). Then small ulcers repeatedly developed on both feet and were associated with reflux esophagitis. In 1998, biopsy revealed deposition of amyloid, a protein in the duodenum, leading to a diagnosis of secondary amyloidosis. In 1999, amyloid deposition was also detected in the rectum. She developed cardiac failure and renal failure in December, leading to hemodialysis. Her cardiac function recovered to normal, but her intestinal movement was markedly reduced. In February of 2000, she suddenly exhibited cardiopulmonary standstill and died. Autopsy revealed severe deposition of amyloid in the heart, many small fibroid foci, and necrotic foci. There was also severe deposition of amyloid in the kidneys and concentric intimal hypertrophy of small arteries in the kidneys. Moreover, fibrosis of the internal circular muscle layer was observed from the esophagus to the colon, with severe deposition of amyloid. Although SSc is rarely complicated by secondary amyloidosis, we think it necessary to take into consideration the complications of secondary amyloidosis in the treatment of patients with long-term SSc.
A 6-year-old boy visited our department with a one month history of a skin lesion on the face. He had been taking sodium bromide, 1.2 g/day, as an anticonvulsant for three months prior to the onset of the lesion. Physical examination showed erythrmatous, pustular, and nodular lesions with scaly crusts on the face. The serum bromide level was highly increased (150 mg/dl, normal 0 to 0.5 mg/dl). Cultures for bacteria, fungi, and atypical acid-fast bacilli were all negative. A skin biopsy specimen showed epidermal hyperplasia with downward proliferation of the epidermis. In the dermis, there was a dense diffuse infiltrarion of neutrophils accompanied by extensive extravasations of erythrocytes and abscesses within dilated infundibula. The diagnosis of bromoderma was made and sodium bromide was discontinued. The skin lesions healed leaving minimal scarring in two months.