Case report of Schöpf-Schulz-Passarge syndrome resulting from a missense mutation, p.Arg104Cys, in WNT10A.

Schöpf-Schulz-Passarge syndrome (SSPS) is a rare ectodermal dysplasia characterized by cysts of the eyelids, hypodontia, hypotrichosis, palmoplantar keratosis and onychodystrophy, and it is not common in Asia according to the published work. This autosomal recessive disorder was believed to result from mutations in the WNT10A gene. We report a 54-year-old Taiwanese man with SSPS resulted from a homozygous mutation (p.Arg104Cys) in WNT10A. This mutation has not been reported in odonto-onycho-dermal dysplasia but was demonstrated to link with dental abnormalities. This report implies the significance of WNT10A gene mutation in ectodermal dysplasia and highlights the clinical features of SSPS.

Rapid detection of dermatophytes and Candida albicans in onychomycosis specimens by an oligonucleotide array.

BACKGROUND: Onychomycosis is a fungal infection of nails, leading to the gradual destruction of the nail plate. Treatment of onychomycosis may need long-time oral antifungal therapy that can have potential side effects, thus accurate diagnosis of the disease before treatment is important. Culture for diagnosis of onychomycosis is time-consuming and has high false-negative rates. To expedite the diagnosis, an oligonucleotide array, based on hybridization between immobilized oligonucleotide probes and PCR products, for direct detection of dermatophytes and Candida albicans in clinical specimens was evaluated. METHODS: Species-specific oligonucleotide probes designed from the internal transcribed spacer (ITS) regions of the rRNA gene were immobilized on a nylon membrane. The assay procedures consisted of PCR amplification of the ITS using universal primers, followed by hybridization of the digoxigenin-labeled amplicons to probes on the array. Thirty two nail samples (29 patients) were analyzed by the array, and the results were compared with those obtained by culture. Array-positive but culture-negative samples were confirmed by cloning and re-sequencing of the amplified ITS and by reviewing patient's clinical data. The total recovery of culture and confirmed array-positive but culture-negative results was considered 100% and was used for performance evaluation of both methods. RESULTS: Concordant results were obtained in 21 samples (10 positives and 11 negatives) by both methods. Eleven samples were array-positive but culture-negative; among them, 9 samples were considered true positives after discrepant analysis. Comparing with culture, the array had significantly higher sensitivity [100% (95% CI 82.2% -100%) vs 52.6% (28.9% -75.5%), p <0.001] and negative predictive value [100% (71.3% -100%) vs 59.1% (36.4% -79.3%), p <0.05), while no significant differences were observed in specificity (84.6% vs 100%, p =0.48) and positive predictive value (90.5% vs 100%, p =1.0). The whole procedures of the array were about 24 h, whilst results from culture take 1 to 3 weeks. CONCLUSIONS: The array offers an accurate and rapid alternative to culture. Rapid diagnosis can expedite appropriate antifungal treatment of onychomycosis. However, the single site nature of this study conducted at a referral hospital invites caution.

The evolution of clinicopathologic features in eruptive lichen planus: a case report and review of literature.

"Eruptive" or "exanthematous" lichen planus (LP) is a rare variant of lichen planus. Here we report a middle-aged woman with a 6-month history of episodic eruptive LP presenting as generalized, erythematous, flat-topped, round, polygonal, or umbilicated papules and hyperpigmented macules. The disease was under good control with continuous low-dose prednisolone over one year. We had the opportunity to correlate the clinical and pathologic findings based on histopathologic examination of three separate skin lesions that appeared to represent different stages of evolution. Recognition of these 3 chronological manifestations (polygonal papule in active inflammation, centrally umbilicated papule in involution, and hyperpigmented macule in resolution) can aid the diagnosis.

A novel splice mutation in the ATP2C1 gene in a woman with concomitant psoriasis vulgaris and disseminated Hailey-Hailey disease.

Concurrent psoriasis vulgaris and Hailey-Hailey disease is very rare. The clinical and pathologic findings of widespread Hailey-Hailey disease in a 48-year-old woman with pre-existing generalized psoriasis vulgaris were described. In our patient, the vesicular eruption of Hailey-Hailey disease was obscured clinically by the psoriatic lesions. The diagnosis of both diseases was confirmed pathologically. The patient had a total of five skin biopsies performed over the neck, flank area, back, pubic area, and a finger. Acantholytic dyskeratosis, changes suggestive of Hailey-Hailey disease, were found in four specimens, psoriasis in two specimens, and both diseases in one specimen. The diagnosis of Hailey-Hailey disease was further confirmed by detecting a novel splice mutation (832G>A) in the ATP2C1 gene. Our case illustrated that diagnosis of disseminated Hailey-Hailey disease may easily be missed in a patient with a pre-existing generalized pruritic eruption, such as psoriasis. The appearance of eczematous vesicular eruption or eroded intertrigo-like lesions in a patient with pre-existing generalized eruption should raise a suspicion of Hailey-Hailey disease.

Demodicosis: a clinicopathological study.

BACKGROUND: Demodex mites are common commensal organisms of the pilosebaceous unit in human beings and have been implicated in pityriasis folliculorum, rosacea-like demodicosis, and demodicosis gravis. OBJECTIVE: We sought to describe the spectrum of clinicopathological findings and therapeutic responses of demodicosis in Taiwanese patients. METHODS: We conducted a retrospective study to review clinicopathologic findings and therapeutic responses of 34 cases of diagnosed demodicosis. RESULTS: Fifteen cases with positive results of potassium hydroxide examination, standardized skin surface biopsy specimen, and/or skin biopsy specimen, and resolution of skin lesions after anti-Demodex treatment were included for final analysis. Nineteen cases were excluded because of insufficient positive data to make a definite diagnosis. There were 4 male and 11 female patients (age 1-64 years, mean age 38.7 years). The disease was recurrent or chronic with a duration ranging from 2 months to 5 years (mean 15.7 months). The skin lesions were acne rosacea-like (n = 8), perioral dermatitis-like (n = 5), granulomatous rosacea-like (n = 1), and pityriasis folliculorum (n = 1). Skin biopsy was performed in 7 patients. Overall, the histopathology was characterized by: (1) dense perivascular and perifollicular lymphohistiocytic infiltrates, often with abundant neutrophils and occasionally with multinucleated histiocytes; (2) excessive Demodex mites in follicular infundibula; and (3) infundibular pustules containing mites or mites in perifollicular inflammatory infiltrate. The skin lesions resolved after treatment including systemic metronidazole, topical metronidazole, crotamiton, or gamma benzene hexachloride. LIMITATIONS: Small sample size and a fraction of patients without long-term follow-up are limitations. CONCLUSION: Demodicosis should be considered in the differential diagnosis of recurrent or recalcitrant rosacea-like, granulomatous rosacea-like, and perioral dermatitis-like eruptions of the face. Potassium hydroxide examination, standardized skin surface biopsy, skin biopsy, or a combination of these are essential to establish the diagnosis.

Identification of dermatophytes by sequence analysis of the rRNA gene internal transcribed spacer regions.

Identification of dermatophytes using the traditional method is sometimes problematic because of atypical microscopic or macroscopic morphology. The aim of this study was to evaluate the feasibility of using sequencing of the ribosomal internal transcribed spacer (ITS)1 and ITS2 regions for identification of 17 dermatophyte species. The ITS regions of 188 strains (62 reference strains and 126 clinical isolates) were amplified by PCR and sequenced. Species identification was made by sequence comparison with an in-house database comprising ITS sequences of type or neotype strains or by blast searches for homologous sequences in public databases. Strains producing discrepant results between conventional methods and ITS sequence analysis were analysed further by sequencing the D1-D2 domain of the large-subunit rRNA gene for species clarification. The identification rates by ITS1 and ITS2 sequencing were higher than 97 %. Based on reference sequences of type or neotype strains, it was noted that most strains of Trichophyton mentagrophytes were misidentifications of Trichophyton interdigitale. In addition, barcode sequences were present in species of the Microsporum canis complex and Trichophyton rubrum complex. These barcode sequences are useful for species delineation when the results of ITS sequencing are ambiguous. In conclusion, ITS sequencing provides a very accurate and useful method for the identification of dermatophytes.

High-frequency intragenomic heterogeneity of the ribosomal DNA intergenic spacer region in Trichophyton violaceum.

The intergenic spacer (IGS) of the rRNA genes was analyzed from the dermatophyte Trichophyton violaceum isolated from cases of tinea capitis in Taiwan and Iran. T. violaceum strains were cultured from different colonies, from single conidial colonies derived by dilution plating, and from micromanipulation of single conidia from clinical samples. A ribosomal DNA probe hybridizing to multiple EcoRI fragments was used to compare restriction fragment length polymorphisms in different T. violaceum isolates. The arthroconidia of T. violaceum that form in vivo during infection were shown to contain a single nucleus by 4',6'-diamidino-2-phenylindole staining. IGS regions from an isolate cultured from a single conidium were amplified, cloned, and sequenced. The results identified that heterogeneity exists between IGS regions within a single T. violaceum genome due to different copy numbers of a 171-bp tandem repeat. This suggests that the IGS of T. violaceum is partially excluded from the concerted evolution of the rRNA gene locus. The heterogeneous character of the IGS regions in T. violaceum contrasts with the closely related dermatophyte Trichophyton rubrum, posing further questions on the phylogeny and the evolution of dermatophyte fungi.

Identification of dermatophytes by an oligonucleotide array.

Species of dermatophytes are classified into three anamorphic (asexual) genera, Epidermophyton, Microsporum, and Trichophyton. Conventional methods used to identify dermatophytes are often lengthy and may be inconclusive because of atypical microscopic or colony morphology. Based on the internal transcribed spacer 1 (ITS-1) and ITS-2 sequences of the rRNA genes, an oligonucleotide array was developed to identify 17 dermatophyte species. The method consisted of PCR amplification of the ITS regions using universal primers, followed by hybridization of the digoxigenin-labeled PCR products to an array of oligonucleotides (17- to 30-mers) immobilized on a nylon membrane. Of 198 dermatophyte strains and 90 nontarget strains tested, the sensitivity and specificity of the array were 99.5% and 97.8%, respectively. The only strain not identified (Microsporum audouinii LMA 597) was found to have a nucleotide insertion at the ITS-2 region where the probe was designed. Two nontarget strains, Microsporum equinum LMA 40396666 and Trichophyton gourvilii var. intermedium CBS 170.65, were misidentified as Microsporum canis and Trichophyton soudanense, respectively. Sequence analysis of the ITS regions revealed that the two misidentified strains displayed high sequence homology with the probes designed for M. canis and T. soudanense, respectively. The present method can be used as a reliable alternative to conventional identification methods and can be completed with isolated colonies within 24 h.

Fusariosis occurring in an ulcerated cutaneous CD8+ T cell lymphoma tumor.

Fusarium species have recently emerged as the second most common pathogenic mold in immunocompromised patients, and they are moderately resistant to most antifungal agents. The skin lesions of disseminated fusariosis typically manifest as multiple red or violaceous macules or nodules, often ulcerated and covered by a black eschar. We report a case of cutaneous fusariosis in a patient with long-standing hypopigmented mycosis fungoides. The infection was successfully treated with a 3-month course of oral voriconazole. The present case is unusual in that the infection occurred within a pre-existing, ulcerated lesion of cutaneous CD8+ lymphoma, resulting clinically in confusion with pyoderma gangrenosum and necrosis of lymphoma. A high index of suspicion will prompt a timely biopsy as well as isolation of the fungus, and early institution of systemic antifungal therapy.

Histopathology of persistent papules and plaques in adult-onset Still's disease.

BACKGROUND: Persistent plaques and linear pigmentation have been reported as specific skin lesions in some patients with adult-onset Still's disease (AOSD). OBJECTIVE: We sought to characterize the histologic findings of AOSD-associated persistent rash in 11 cases and correlate the histologic findings with the clinical features. METHODS: From 1988 to 2004, 17 cases fulfilling Yamaguchi's criteria for AOSD in our hospital were reviewed and 11 (65%) manifested persistent papules and plaques. The pathology of 13 biopsy specimens of persistent eruption from 9 patients was reviewed. RESULTS: The 11 patients consisted of 3 men and 8 women with age of onset ranging from 19 to 67 years (average 34.7 years). Evanescent Still's rash was recorded in 9 patients. The persistent rash manifested as pruritic, red, violaceous, or brownish scaly or crusted lichenoid papules and plaques usually widely distributed over the trunk, neck, face, and extensor sides of the extremities. Lesions arranged in a bizarre linear pattern resulting from scratching were noted in some patients. Three patients died of severe disease, systemic complications, or both. The histology of persistent papules and plaques was characterized by: (1) multiple individual necrotic keratinocytes, singly or in aggregates, mainly located in the upper epidermis, including the normal or parakeratotic horny layer; and (2) infiltration of lymphocytes and neutrophils in the papillary and middermis. Other less common findings included basal vacuolar alteration, nuclear dust, and subcorneal or intracorneal pustules. CONCLUSIONS: A clinically and pathologically distinct form of persistent lichenoid eruption was commonly observed in our patients with AOSD. The combination of multiple individual necrotic keratinocytes in the upper epidermis and a dermal infiltrate of neutrophils allow for histologic differentiation of this persistent eruption from most other lichenoid and interface dermatitides and may facilitate an earlier diagnosis of AOSD.

Clinical resemblance of widespread bullous fixed drug eruption to Stevens-Johnson syndrome or toxic epidermal necrolysis: report of two cases.

Widespread bullous fixed drug eruption (FDE) is the most severe form of FDE and may be mistaken clinically for Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN). We report two cases of generalized bullous drug eruption with extensive epidermal necrosis and detachment mimicking SJS/TEN overlap and TEN, respectively. The first patient, a 78-year-old man, developed SJS/TEN-like eruption with widespread dusky red patches and denuded areas shortly after taking multiple nonsteroidal antiinflammatory drugs (NSAIDs). Histopathology showed vacuolar interface dermatitis with numerous necrotic keratinocytes and a superficial and deep perivascular infiltrate containing lymphocytes, eosinophils, neutrophils and melanophages. These findings are consistent with FDE. The second patient, a 61-year-old woman, had three episodes of near-total body epidermal detachment shortly after taking NSAIDs. TEN was diagnosed clinically in all three episodes without pathologic confirmation. FDE was suspected due to lack of involvement of two mucosal sites and uneventful recovery. These cases highlight the importance of considering severe bullous FDE in the differential diagnosis of SJS and TEN, and the necessity of skin biopsy in such cases.