Novel PORCN mutations in focal dermal hypoplasia.

Focal dermal hypoplasia (FDH), Goltz or Goltz-Gorlin syndrome, is an X-linked dominant multisystem disorder characterized primarily by involvement of the skin, skeletal system and eyes. We screened for mutations in the PORCN gene in eight patients of Belgian and Finnish origin with firm clinical suspicion of FDH. First, we performed quantitative PCR (qPCR) analysis to define the copy number at this locus. Next, we sequenced the coding regions and flanking intronic sequences of the PORCN gene. Three de novo mutations were identified in our patients with FDH: a 150-kb deletion removing six genes including PORCN, as defined by qPCR and X-array-CGH, and two heterozygous missense mutations; c.992T>G (p.L331R) in exon 11 and c.1094G>A (p.R365Q) in exon 13 of the gene. Both point mutations changed highly conserved amino acids and were not found in 300 control X chromosomes. The three patients in whom mutations were identified all present with characteristic dermal findings together with limb manifestations, which were not seen in our mutation-negative patients. The clinical characteristics of our patients with PORCN mutations were compared with the previously reported mutation-positive cases. In this report, we summarize the literature on PORCN mutations and associated phenotypes.

A feasibility study of realtime teledermatology in Finland.

We conducted a feasibility study of teleconsultation in dermatology using low-cost equipment. Patients and their general practitioners took part in consultations from the Primary Health Care Centre in Ikaalinen with a dermatologist 55 km away at the Tampere University Hospital (TAUH). Consultations were performed using standard commercial videoconferencing equipment, a modified document camera and a dermatoscope. A single ISDN line (128 kbit/s) was used for the connection. During the eight months of the study, 25 patients participated in a teledermatology consultation. Their mean age was 45 years (range 4-92). The average time the patient spent in travelling to the videoconsultation (i.e. one way) was 24 min (range 5-65 min). The mean time spent in the teleconsultation was 15 min (range 5-30 min). After the teleconsultation, patients' treatments changed in 19 cases (76%), diagnoses were changed in 13 cases (52%) and 18 patients (72%) did not need to go to the TAUH. The equipment was generally reliable and easy to use. However, the dermatoscope was not very useful and only one of the consultations relied mainly on it. The cost of the teleconsultations for the 18 patients who avoided travel to the TAUH was FM18,627. The total costs for the 18 conventional consultations in the TAUH would have been FM18,034. The main economic benefits of the videoconferencing were attributable to the reduced travelling and hospital costs. The economic benefits of medical education were more difficult to quantify.

Reactivity of tixocortol pivalate-positive patients in intradermal and oral provocation tests.

Pivalone/tixocortol pivalate commonly yields positive reactions in the patch test series. The clinical relevance of these positive reactions was investigated in more detail. In the standard patch test series 5.6% (73 of 1306) of the patients were positive to corticosteroids, 5.2% to 0.1% tixocortol pivalate in ethanol (Pivalone nasal spray diluted 1:10) and 2.3% to 1% hydrocortisone butyrate in ethanol. Some of the patients were tested in parallel with Pivalone and 1% tixocortol pivalate in petrolatum. The former test reagent yielded some false-positive reactions, whereas with the latter, some allergic responses were missed. Intradermal tests with the succinate esters of hydrocortisone, methylprednisolone and prednisolone were performed with 52 patients positive to Pivalone. Of these 76.9% (40 of 52) were positive in the intradermal tests; 38 to hydrocortisone, 35 to methylprednisolone and 30 to prednisolone. Twelve patients who had been positive in the intradermal tests were challenged orally with corticosteroids and they all showed positive reactions to hydrocortisone, methylprednisolone or prednisolone. The patients developed localized reactions at the sites of previous eczema or positive skin tests or diffuse erythema or exanthema. The oral doses of hydrocortisone eliciting positive delayed skin reactions ranged from 20 to 200 mg. Reactivity to tixocortol pivalate is closely related to sensitivity to hydrocortisone, methylprednisolone and prednisolone, but high oral doses of these corticosteroids may be required to produce allergic symptoms.

Diagnostic value of the lymphocyte proliferation test in nickel contact allergy and provocation in occupational coin dermatitis.

The lymphocyte proliferation test (LPT) was compared with the patch test in the diagnosis of nickel contact sensitivity. Of the 21 subjects with nickel contact allergy, the patch test detected 20 (95%). The subject remaining negative in the patch test was positive in the intradermal test. 18/21 subjects with nickel contact sensitivity were positive in the LPT, whereas in the control group 2/23 subjects were false positive. These results were obtained at nickel sulfate concentrations of less than 10 micrograms/ml, higher concentrations led to nonspecific lymphocyte stimulation. 3 nickel-sensitive cashiers with suspected coin contact-induced deterioration of their hand eczema were challenged by having them count nickel-containing coins daily for 15 min. 2 of them developed vesicular eczema on their palms and fingers in 2 to 3 days. The present results show that the LPT is a reliable additional test in the diagnosis of nickel contact sensitivity. Furthermore, provocation is a valuable procedure when assessing the relevance of nickel contact in occupational hand eczema in certain occupations.

A study of bone formation in osteoma cutis employing biochemical, histochemical and in situ hybridization techniques.

A female presenting multiple osteoma cutis lesions without underlying endocrinological disturbance was studied. Histologically, lesions revealed true bone formation with multiple osteoblastic cells. This was confirmed by demonstrating high alkaline phosphatase activity and osteonectin expression in osteoma cutis lesions. Interestingly, tenascin and type III procollagen were in close association to bony lesions, indicating that these matrix proteins may be somehow involved in bone formation. In situ hybridization revealed fibroblastic cells around bony lesions, which actively deposited type I collagen and osteonectin. One of the activators of bone formation, TGF beta, was also present in some osteoblastic cells. The results thus indicate that in osteoma cutis, fibroblasts have the ability to differentiate into osteoblastic cells, which have some properties of osteoblasts, such as high alkaline phosphatase activity and a high expression of osteonectin.

Osteomyelitis-like bone lesions in acne fulminans.

Two young males with acne fulminans (AF) are described. In addition to severe skin lesions, they had musculoskeletal symptoms including bacteriologically negative osteolytic lesions in the clavicles. Both patients received antibiotics for suspected septic infections. The response was unsatisfactory in both patients, and combination treatment with prednisolone was started. A favourable response was observed, and a relapse occurring in the first patient was controlled by steroids alone. The possible pathomechanism of bone lesions in AF is discussed.

Desmoplastic trichoepithelioma: clinico-pathological features and immunohistochemical study of the basement membrane proteins, laminin and type IV collagen.

Six desmoplastic trichoepitheliomas (DT) from four patients were studied immunohistochemically, using antibodies to the human PI fragment of laminin and the 7S domain of type IV collagen. The staining of the basement membrane around the tumour clusters was distinct and continuous in most areas, but there were discontinuities and a granular appearance of the basement membrane in the areas of keratinized cysts and calcification around some unorganized epithelial cell nests. The discontinuities of the basement membranes may be a sign of epithelial degeneration or altered differentiation rather than malignancy.