Lower serum fibroblast activation protein shows promise in the exclusion of clinically significant liver fibrosis due to non-alcoholic fatty liver disease in diabetes and obesity.

UNLABELLED: Non-alcoholic fatty liver disease (NAFLD) is common in diabetes and obesity but few have clinically significant liver fibrosis. Improved risk-assessment is needed as the commonly used clinical-risk algorithm, the NAFLD fibrosis score (NFS), is often inconclusive. AIMS: To determine whether circulating fibroblast activation protein (cFAP), which is elevated in cirrhosis, has value in excluding significant fibrosis, particularly combined with NFS. METHODS: cFAP was measured in 106 with type 2 diabetes who had transient elastography (Cohort 1) and 146 with morbid obesity who had liver biopsy (Cohort 2). RESULTS: In Cohort 1, cFAP (per SD) independently associated with median liver stiffness (LSM) ≥ 10.3 kPa with OR of 2.0 (95% CI 1.2-3.4), p=0.006. There was 0.12 OR (95% CI 0.03-0.61) of LSM ≥ 10.3 kPa for those in the lowest compared with the highest FAP tertile (p=0.010). FAP levels below 730 pmol AMC/min/mL had 95% NPV for LSM ≥ 10.3 kPa and reclassified 41% of 64 subjects from NFS 'indeterminate-risk' to 'low-risk'. In Cohort 2, cFAP (per SD), associated with 1.7 fold (95% CI 1.1-2.8) increased odds of significant fibrosis (F ≥ 2), p=0.021, and low cFAP reclassified 49% of 73 subjects from 'indeterminate-risk' to 'low-risk'. CONCLUSIONS: Lower cFAP, when combined with NFS, may have clinical utility in excluding significant fibrosis in diabetes and obesity.

Tinea capitis in a paediatric population.

Tinea capitis is an increasing problem in Europe. The pattern of infection is changing with an increase in pathogenic anthropophilic dermatophytes particularly Trichophyton tonsurans. We aimed to determine the frequency of tinea capitis in a paediatric population attending dermatology outpatients and examine the clinical spectrum of disease. A retrospective analysis was performed of all laboratory proven tinea capitis cases presenting to the dermatology outpatient department at The Children's University Hospital, Temple Street over an 18-month period (1st January 2004 to 30th of June 2005 inclusive). Sixty-two children had tinea capitis of whom 53 (85.5%) were of African descent. Thirty-five (56%) were male and 27 female (44%). The average age at presentation was 4.02 years (age range 1-163 months) with five cases occurring in children less than one year of age. The most common pathogen was the anthropophilic dermatophyte Trichophyton tonsurans, accounting for 47 (75.8%) of all cases of tinea capitis. Eight (12.9%) were secondary to Microsporum ferrigineum, 2 (3.2%) secondary to Trichophyton violaceum, both Trichophyton soudanese and Trichophyton verruosum accounted for 1.6% each. The zoophilic organism Microsporum canis was diagnosed in 3 cases (4.8%). Presenting signs included scaling of the scalp (35.47%), scaling of the scalp and alopecia (53.24%), and alopecia and kerion (11.29%/o). The duration of symptoms was recorded in 52 patients with the average duration 8.38 months (range 0.5-72 months). In 20 cases an associated skin involvement on other areas of the body was recorded. All patients at diagnosis were either on no, suboptimal or inappropriate treatment. The prevalence of tinea capitis is increasing in this hospital based cohort. The main pathogen is now Trichophyton tonsurans. Children of African descent are at increased risk of infection. The diagnosis is poorly recognized and needs to be highlighted as a public health issue. There is a need for community based prevalence studies.

Increased risk of squamous cell carcinoma in junctional epidermolysis bullosa.

Non-Herlitz junctional epidermolysis bullosa (JEB) is an autosomal recessive genodermatosis characterized by skin fragility and blistering. It is usually caused by mutations in the genes encoding the basement membrane proteins laminin 5 or type XVII collagen. Clinically, impaired wound healing and chronic erosions cause major morbidity in affected patients. Previously it was thought that these individuals, unlike patients with dystrophic EB, did not have an increased risk of developing skin cancer. However, we describe three patients with non-Herlitz JEB (aged 42, 56 and 75 years) who developed cutaneous squamous cell carcinomas (SCCs). The tumours were well-differentiated in two cases, but one patient had multiple primary SCCs that were either well- or moderately differentiated. Most cases of SCC in non-Herlitz JEB described have occurred in those with laminin 5 defects and on the lower limbs. These clinicopathological observations have important implications for the management of patients with this mechanobullous disorder as well as providing further insight into the biology of skin cancer associated with chronic inflammation and scarring.

Neutrophilic eccrine hidradenitis in two neutropaenic patients.

We describe two patients, who presented with erythematous facial plaques, in keeping with neutrophilic eccrine hidradenitis, during chemotherapy for acute myeloid leukaemia. Both patients were neutropaenic and febrile. Histology showed a dermal neutrophilic infiltrate around the eccrine glands with gland destruction. The importance of recognizing this disorder is to prevent the inappropriate use of antibiotics as it is self limiting.

Alpha 6 beta 4 integrin abnormalities in junctional epidermolysis bullosa with pyloric atresia.

Junctional epidermolysis bullosa with pyloric atresia (JEB-PA) (MIM 226730) is an autosomal recessive disorder resulting from mutations in the genes encoding alpha 6 beta 4 integrin (ITGA6 and ITGB4). Clinically, it is characterized by mucocutaneous fragility and gastrointestinal atresia, which most commonly affects the pylorus. Additional features of JEB-PA include involvement of the urogenital tract, aplasia cutis and failure to thrive. While most affected individuals have a poor prognosis resulting in death in infancy, others have milder clinical features and a better prognosis. We report two previously undescribed homozygous ITGB4 mutations in two unrelated families, which resulted in severe skin blistering, pyloric atresia and lethality in infancy. Delineation of the mutations was used to undertake DNA-based prenatal diagnosis in subsequent pregnancies at risk for recurrence in both families. We review all previously published ITGA6 and ITGB4 mutation reports to help define genotype--phenotype correlation in this rare genodermatosis.

A pseudolymphomatous skin reaction secondary to flucloxacillin.

We report the first case of a pseudolymphomatous skin reaction precipitated by flucloxacillin. Skin histology was suggestive of a cutaneous lymphoma, and DNA analysis by single stranded conformational polymorphism (SSCP) demonstrated T-cell receptor gamma gene monoclonality. Withdrawal of flucloxacillin led to immediate clinical improvement and gradual resolution of skin rash and lymph nodes.

Striate palmoplantar keratoderma resulting from desmoplakin haploinsufficiency.

Recently, the first example of a human mutation in the gene encoding the desmosomal plaque protein, desmoplakin, has been described in a patient with autosomal dominant striate palmoplantar kerato-derma. We now report a further case of a desmoplakin mutation in a proband with striate palmoplantar keratoderma that also results in a null allele and haploinsufficiency. The mutation was a heterozygous G > A transition at the donor + 1 site of intron 7 of the desmoplakin gene (939 + 1 G > A; Genbank M77830). The aberrant splicing leads to retention of the entire intron 7, which contains a premature termination codon within the N-terminal domain of the peptide. Because the mutant null allele could not be identified on cDNA sequencing, we determined by polymerase chain reaction the exon-intron organization of the desmoplakin gene to facilitate analysis of genomic DNA. The gene spans approximately 45 kb of chromosome 6 and comprises 24 exons ranging in size from 51 bp to 3922 bp. We have also characterized fully the 3'UTR of the desmoplakin cDNA. This study demonstrates the relevance of haploinsufficiency for desmoplakin in the pathogenesis of this genodermatosis. Assessment of family members bearing the mutant allele also emphasizes the significance of an individual's age and exposure to skin trauma in manifesting full phenotypic expression of the disorder.

Recalcitrant viral warts treated by diphencyprone immunotherapy.

Recalcitrant viral warts are a troublesome therapeutic problem. Immunotherapy with the universal allergic contact sensitizer diphencyprone (DCP) has been used successfully in such cases. We have reviewed our experience of the use of DCP in the treatment of resistant hand and foot warts during an 8-year period. Sixty patients were sensitized to DCP during this time; the median duration of warts was 3 years. Twelve patients defaulted from treatment. Of the remaining 48 individuals, 42 (88%) cleared of all warts. The median number of treatments to clear was five (range one to 22) and the median time to clear was 5 months (range 0.5-14). Adverse effects occurred in 27 of 48 patients (56%), most commonly painful local blistering (n = 11), blistering at the sensitization site (n = 9), pompholyx-like reactions (n = 7) and eczematous eruptions (n = 4). Three of those who defaulted did so due to side-effects, one became pregnant and eight dropped out for unknown reasons. Three of the 48 patients who cleared or had at least six treatments also discontinued DCP therapy due to side-effects, but most tolerated treatment well. Twenty-five patients were followed up for periods of 1 month to 8 years (median 2 years) and none had a recurrence. DCP immunotherapy is an effective option for the treatment of recalcitrant viral warts but patients must be motivated to attend for sequential applications and must be warned about potential uncomfortable side-effects.

Analysis of Chinese herbal creams prescribed for dermatological conditions.

OBJECTIVE: To determine whether Chinese herbal creams used for the treatment of dermatological conditions contain steroids. DESIGN: 11 herbal creams obtained from patients attending general and paediatric dermatology outpatient clinics were analysed with high resolution gas chromatography and mass spectrometry. SETTING: Departments of dermatology and clinical biochemistry. MAIN OUTCOME MEASURE: Presence of steroid. RESULTS: Eight creams contained dexamethasone at a mean concentration of 456 micrograms/g (range 64 to 1500 micrograms/g). All were applied to areas of sensitive skin such as face and flexures. CONCLUSION: Greater regulation needs to be imposed on Chinese herbalists to prevent illegal and inappropriate prescribing of potent steroids.

Analysis of Chinese herbal creams prescribed for dermatological conditions.

OBJECTIVE: To determine whether Chinese herbal creams used for the treatment of dermatological conditions contain steroids. DESIGN: 11 herbal creams obtained from patients attending general and pediatric dermatology outpatient clinics were analyzed with high resolution gas chromatography and mass spectrometry. SETTING: Departments of dermatology and clinical biochemistry. ; MAIN OUTCOME MEASURE: Presence of steroid. RESULTS: Eight creams contained dexamethasone at a mean concentration of 456 mug/g (range 64 to 1500 mug/g). All were applied to areas of sensitive skin such as face and flexures. CONCLUSION: Greater regulation needs to be imposed on Chinese herbalists to prevent illegal and inappropriate prescribing of potent steroids.