Psychosomatic factors in first-onset alopecia areata.

Although the onset of alopecia areata has often been anecdotally linked with emotional stress, findings from the few controlled studies have not been univocal. The authors compared outpatients experiencing a recent onset of alopecia areata (N=21) with outpatients affected by skin conditions commonly believed as having a low psychosomatic component (N=102). Participants were administered Paykel's Interview for Recent Life Events, the Experiences in Close Relationships scale, the 20-item Toronto Alexithymia Scale, and the Multidimensional Scale of Perceived Social Support. Multiple logistic regression was used to control for age and gender. The total number of recent life events (last 12 months) was not different between the alopecia patients and the comparison subjects. Also, the alopecia patients and the comparison subjects did not differ in terms of the number of undesirable or major events. The comparison subjects even experienced a greater number of uncontrollable events. Alopecia areata tended to be associated with high avoidance in attachment relationships, high alexithymic characteristics, and poor social support. The results suggest that personality characteristics might modulate individual susceptibility to alopecia areata.

Risk factors for basal cell carcinoma in a Mediterranean population: role of recreational sun exposure early in life.

OBJECTIVE: To investigate the role of pigmentary traits, different patterns of sun exposure, artificial sources of UV radiation, and lifestyle-related factors on the risk of basal cell carcinoma (BCC) in a Mediterranean population from central-southern Italy. DESIGN: Hospital-based case-control study. SETTING: A referral dermatological hospital in Rome, Italy. PATIENTS: A convenience sample of 166 case patients with histologically confirmed BCC and 158 cancer-free control subjects with minor dermatological conditions observed between March 1995 and June 1997. RESULTS: In the multivariate analysis, the mean number of weeks per year spent at the beach before the age of 20 years was significantly associated with BCC. A dose-response trend was found for subjects who had spent 3 to 4 (odds ratio, 1.8; 95% confidence interval, 0.8-4.4), 5 to 8 (odds ratio, 3.7; 95% confidence interval, 1.5-9.0), or more than 8 (odds ratio, 4.5; 95% confidence interval, 1.9-10.5) weeks per year at the beach (P =.01 for trend). There was a significant association with the presence of actinic keratoses or solar lentigines, whereas no effect was found for skin type, history of sunburns, exposure to nonsolar UV radiation, and lifestyle-related habits such as cigarette smoking, alcohol consumption, and coffee drinking. Subjects reporting a family history of skin cancer had an extremely increased risk of BCC. CONCLUSION: The definite association with recreational sun exposure during childhood and adolescence and the strong relation with family history of skin cancer suggest that genetic predisposition and peculiar exposure patterns to UV radiation are key independent risk factors for the development of BCC in a southern European population.

New type of epidermal nevus syndrome.

An uncommon type of epidermal nevus characterized by systematized bands of non-epidermolytic hyperkeratosis with increased hairiness and follicular hyperkeratosis was observed in a 16-year-old boy who showed, in addition, hemihypoplasia of limbs, brachydactyly, clinodactyly and onychodystrophy. This case cannot be categorized within the group of presently established epidermal nevus syndromes. Most likely, this combination of anomalies represents a new type of epidermal nevus syndrome.

A glutamine insertion in the 1A alpha helical domain of the keratin 4 gene in a familial case of white sponge nevus.

White Sponge Nevus (WSN) is a rare, autosomal dominant disorder that predominantly affects noncornified stratified squamous epithelia. Clinically, it is characterized by the presence of soft, white, and "spongy" plaques in the oral mucosa. The characteristic histopathologic features are epithelial thickening, parakeratosis, and vacuolization of the suprabasal layer of oral epithelial keratinocytes. Mutations in keratin 4 (K4) and keratin 13 (K13) genes have already been demonstrated to be responsible for WSN; the identification of new keratin mutations in a stratified squamous epithelia closely related to epidermis is of relevance for the understanding of the biochemistry of intermediate filaments, and for genotype phenotype correlations. In this study we investigated a 27-y-old, female Italian patient, affected by white asymptomatic oral plaques. Sequence analysis revealed a 3 bp (ACA) heterozygous insertion localized in the helix initiation motif of the 1A alpha helical domain of K4. We report this new K4 gene mutation and describe an amino acid insertion, in the 1A domain, responsible for a keratin disease.

A clinicopathologic study of scarring alopecia due to lichen planus: comparison with scarring alopecia in discoid lupus erythematosus and pseudopelade.

The clinicohistologic findings in 68 patients with lichen planus scarring alopecia (LP) were compared with those of 25 patients with discoid lupus erythematosus of the scalp (DLE) and 25 with pseudopelade (PP). The combination of diffuse scaling, erythema, telangiectases, and mottled hyperpigmentation within areas of scarring alopecia was a distinctive feature of DLE, whereas the clinical picture of PP was indistinguishable from that seen in 29 patients with LP. In most patients with LP, the histologic changes involved only the follicles and the perifollicular dermis. Less frequently, the inflammatory process extended to the epidermis and the papillary dermis. In all cases, histopathologic features allowed LP to be distinguished from DLE regardless of the stage of the disease. The finding of a bandlike fibrotic thickening of the papillary dermis accompanied by fibrotic tracts at sites of destroyed follicles appeared to be a hallmark of "burnt out" lesions of LP. This histologic clue may be helpful in achieving a specific diagnosis of LP in cases that fulfill the clinical criteria for PP.

ATP2A2 mutations in Darier's disease: variant cutaneous phenotypes are associated with missense mutations, but neuropsychiatric features are independent of mutation class.

Darier's disease (DD) is an autosomal dominant skin disorder characterized clinically by multiple keratotic papules, and histologically by focal loss of adhesion between epidermal cells (acantholysis) and by abnormal keratinization. Variant forms of cutaneous phenotype, sometimes familial, have been described. Associated neuropsychiatric features, including mental handicap, schizophrenia, bipolar disorder and epilepsy, have also been reported. The cause of DD was shown recently to be mutation in the ATP2A2 gene at 12q24.1, which encodes the sarco-endoplasmic reticulum calcium ATPase type 2 (SERCA2). Here, we show that while both common isoforms of SERCA2 are expressed in the cytoplasm of cultured keratinocytes and fibroblasts, in adult skin sections only the longer isoform, SERCA2b, was expressed abundantly in epidermal structures. Extended mutation analysis in European DD patients using single-strand conformation polymorphism and/or direct sequencing identified 40 different patient-specific mutations in 47 families. The majority (23/40) were likely to result in nonsense-mediated RNA decay. The remaining 17 were missense mutations distributed throughout the protein and were associated significantly with atypical clinical features. The clearest association was with the familial haemorrhagic variant where all four families tested had a missense mutation. Three of the families (one Scottish family and two unrelated Italian families) exhibited the same N767S substitution in the M5 transmembrane domain, and a fourth family, from Sweden, had a C268F substitution in the M3 transmembrane domain. Neuropsychiatric features did not appear to be associated with a specific class of mutation and may be an intrinsic, but inconsistent, effect of defective ATP2A2 expression.

Searching for psoriasis susceptibility genes in Italy: genome scan and evidence for a new locus on chromosome 1.

Psoriasis is a chronic inflammatory dermatitis, affecting approximately 2% of the population. Major clinical features include red, scaly patches on scalp, elbows, and knees, with or without severe arthritis. Several putative susceptibility loci have been mapped by parametric and non-parametric linkage analysis to chromosome regions 2p, 4q, 6p, 8q, 16q, 17q, and 20p; however, the most significant results and confirmation of linkage are only available for the 17q and 6p chromosome regions at present. In this study, 22 multiplex Italian families were investigated for linkage to 6p and 17q susceptibility regions, using a set of four microsatellites. These analyses failed to detect significant linkage with any of the examined markers. A genome-wide scan was then performed on one of the largest pedigrees, searching for an additional susceptibility locus. This study disclosed a putative linkage to chromosome 1cen-q21 markers. When these microsatellites were analyzed in the remaining families of the sample, a significant linkage was observed using both parametric and non-parametric methods. The highest two-point lod score value was obtained with D1S305 marker (3.75 at 0 = 0.05). Non-parametric analysis at this locus also demonstrated a significant excess of allele sharing (p = 0.0001).

180-kDa bullous pemphigoid antigen defective generalized atrophic benign epidermolysis bullosa: report of four cases with an unusually mild phenotype.

Generalized atrophic benign epidermolysis bullosa (GABEB) is a rare variant of non-lethal junctional epidermolysis bullosa characterized by generalized skin blistering healing with atrophy and by atrophic alopecia with onset in childhood. Other features include mild mucosal blistering, dental abnormalities and nail dystrophy. We report four additional cases of GABEB from two families originating from the same isolated village. The patients shared an unusually mild clinical phenotype with cutaneous blisters strictly limited to trauma sites and rare occurrence of oral mucosal lesions. Scalp, eyelash and eyebrow alopecia was present in only two cases. Immunofluorescence studies showed a markedly reduced expression of the 180-kDa bullous pemphigoid antigen (BP180), and northern analysis of cultured keratinocytes indicated that the gene encoding for BP180 is affected in these GABEB patients.

Koebner phenomenon in an ANCA-positive patient with pyoderma gangrenosum.

A male with pyoderma gangrenosum is reported. The clinical and histological features were typical. The initial lesions resolved with characteristic cribriform scars. A few days after the complete recovery, he developed several necrotizing focal lesions localized to the scarred areas. A further histological examination revealed a granulation tissue rich in neutrophils and signs of necrotizing vasculitis. We found a high titer of circulating perinuclear antineutrophil antibodies (p-ANCA), which are a serological marker for various systemic diseases. An immunological circulating factor has been repeatedly suggested to be the "primum movens" of pyoderma gangrenosum. We discuss the unusual clinical presentation interpreted as a Koebner phenomenon and the possible role of immune factors in enhancing circulating-endothelial cell interactions in relation to the pathogenesis of pyoderma gangrenosum.

Polymerase chain reaction and reverse cross blot hybridization assay for detection of mycobacterial DNA in lupus vulgaris.

For 5 years, an 83-year-old man had been suffering from slightly itchy erythematous plaques with clearcut margins, located on his left thigh and on his right arm; in addition, on his right auricle there was an erythematous patch with yellowish shadings that had appeared about 3 years before and had progressively spread to the temporal-zygomatic region, the chin and the mandibular arch. These lesions were strongly suggestive of lupus vulgaris; however the conventional bacteriological examinations performed on the biopsy specimen from lesional skin were negative. A diagnosis of lupus vulgaris was achieved through the detection of the 16S rRNA gene of Mycobacterium tuberculosis in a skin biopsy of the patient by means of a polymerase chain reaction followed by a reverse cross blot hybridization, a method which allows the identification of different mycobacterial species in a single hybridization procedure.

X-linked dominant chondrodysplasia punctata (Happle syndrome) with uncommon symmetrical shortening of the tubular bones.

We describe the case of a 13-year-old girl suffering from chondrodysplasia punctata, associated with ichthyosis arranged along Blaschko's lines, follicular atrophoderma, cicatricial alopecia and coarse, lusterless hair. The patient also showed a congenital cataract of the right eye, dysplastic facial appearance and symmetrical shortening of the tubular bones. The pathogenetic concept of functional X-chromosome mosaicism is reviewed as well as the recent results obtained by molecular research that have failed, so far, to solve the problem of regional assignment of the underlying X-linked gene.