Biomedical subjects
Publications and source records attributed to R Happle.
We report the quantification of a membrane-bound phospholipase C in human epidermis which is active against the physiologically relevant substrate, phosphatidylinositol 4,5-bisphosphate. The level of this enzyme is significantly increased in the psoriatic lesion, both on a weight and protein basis. Etiological implications of this observation are discussed.
In general, the diagnosis of alopecia areata is not difficult. In children, we have to consider trichotillomania as a differential diagnosis; in adult patients pseudopelade and syphilis have to be taken into account. Investigation of the nails may support the diagnosis and help to assess the degree of activity of the disease. The efficacy of topical immunotherapy using diphencyprone or squaric acid dibutylester has been proved by various study groups. Unilateral comparative studies supported our assumption that the therapeutic response is most probably due to a local immunomodulation. The applicability of this method is limited by the fact that the toxicological data available on the contact allergens used are still incomplete.
A "divided naevus" (or "kissing naevus") is defined as a congenital melanocytic naevus that occurs on adjacent parts of the upper and lower eyelid and may give the appearance of a single lesion when the eye is closed. We report on four cases of this rare naevus. Two of these were examined histologically and showed the features of compound naevi. The unique occurrence in nature of the divided naevus allows conclusions on the site and time of origin not only of the divided naevus, but possibly also of other congenital melanocytic naevi. The divided naevus must originate at the latest during the period of lid fusion, between the 9th and 20th week of gestation. The fact that the fusion involves only epithelial tissue suggests an epithelial origin of congenital melanocytic naevi, which may later develop secondarily into compound or intradermal naevi by way of "dropping-off".
Epidermal naevus of the acanthokeratolytic (epidermolytic) type is a mosaic birth defect. The underlying mutation may also be present in the gonads and can then be transmitted to the next generation. The affected child, however, will always show a diffuse involvement of the entire body in the form of bullous congenital ichthyosiform erythroderma. In other words, the phenotype can be transmitted, but not the mosaic. This explains why acanthokeratolytic epidermal naevus always affects the parent and never the child when it is observed in a family together with bullous congenital ichthyosiform erythroderma.
A 15-year-old girl with the typical signs and symptoms of the CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects) is described. Associated ipsilateral anomalies included systematized hypotrichosis, fused vertebrae, hemivertebrae, pelvic hypoplasia and renal agenesis. During a careful inquiry, her mother reported that during her own adolescence she had linear ichthyosiform skin changes localized in 3 different regions of her body. These plaques had disappeared spontaneously in early adulthood, leaving permanent lesions in the form of hairless streaks and a dystrophic fingernail. Hence this is the first report of a mother-to-daughter transmission of this genodermatosis, lending further support to the proposed concept of X-linked dominant inheritance with lethality for male embryos. We conclude that the mother of a girl suffering from the CHILD syndrome cannot be considered to be unaffected unless a meticulous examination of her skin and bones has ruled out even minimal signs of involvement.
Multiple melanocytic nevi showing an unusual accumulation on the soles of the feet were observed in an 8-year-old boy after he had received chemotherapy for acute lymphatic leukemia. This observation confirms the occurrence of chemically induced melanocytic nevi as well as their affinity for the acral sites.
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In three boys, aged 12.5, 14 and 16 years, respectively, acne of the fulminans type developed after eight to twelve months' administration of 250 mg testosterone weekly or 500 mg every second week. Numerous deep and painful pustules grew, dominantly on the chest and back, in one of the boys also in the face. In addition fever and fatiguability set in, as well as bone and joint pains in some. Erythrocyte sedimentation rate and leukocyte counts were raised. Testosterone was at once discontinued and isotretinoin, in one boy also antibiotics, administered, this treatment lasting for 8 to 13 months. All three boys were left with disfiguring scars. Before testosterone is given to arrest growth in tall boys both patient and parents should be told of these potentially severe side effects.
Dysplastic nevi represent precursor lesions harboring an increased risk of evolving into melanoma. Their association with familial melanoma is usually considered a monogenic syndrome with autosomal dominant transmission. To test this concept we estimated the mutation rates. When derived directly from the sporadic occurrence of the trait, the mutation rate is exceedingly high (0.9%-2.5%), whereas, as estimated with the aid of Haldane's formula it would be 0.007% to 0.02%. Accordingly, newly arising mutation would outnumber eliminated mutations by 100:1. Even if only 80% of all old mutations are passed onto the next generation, this ratio of 100:1 would rapidly change. After only a few generations, 10% of the world population should be affected with the dysplastic nevus "syndrome". The apparent lack of a genetic equilibrium between newly arising and eliminated mutations is not compatible with autosomal dominant inheritance of the dysplastic nevus "syndrome."
Diazolidinyl urea (DU; trade name Germall II), a new broad spectrum preservative, was tested from July 1984 to September 1988 in 2400 consecutive patients with eczemas possibly caused or complicated by a contact allergy. In addition to the European standard series (Trolab), a supplementary test battery including DU 2% in water was used. A sensitization to DU was seen in 13 patients (0.54%). Of 13 patients 7 reacted only to DU, but not to formaldehyde (FA) or FA releasers; in these patients, the reaction can be attributed to sensitivity to DU itself. Six of the 13 patients reacted to DU as well as FA and all FA releasers tested; in these patients, the reaction to DU is probably due to released FA. For practical reasons, DU should be added to the list of FA releasers. In some of the patients, concomitant sensitization to frequent contact allergens such as nickel, cobalt, chromate, or a long history of skin disease could be found; it seems reasonable to assume that in these cases the sensitization to DU was enhanced by an eczematous skin with a reduced barrier function. Patients reacting to FA should be advised to perform a repeated open application test (ROAT) before using a cosmetic containing DU as a preservative, to prevent possible adverse effects from released FA.
The dose response relationship to acitretin in five patients with Darier's disease was investigated. The patients received in the first 3 months 35 mg daily, and the dose was adjusted according to the clinical response. Four of the five patients showed a marked improvement with up to total clearance, although in two patients isomorphic reactions due to a relative overdose were seen. These isomorphic reactions improved with a reduction of dose. We suggest that treatment with acitretin is initiated at 10-25 mg daily with gradual adjustment of the dose.
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The authors report a case of siblings in whom circumscribed plantar keratoderma developed during early childhood. The keratotic areas increased with age and also affected the dorsal aspects of the digital joints. In addition, a markedly progressive disturbance in sound perception occurred in both children from age 4 onwards. This observation confirms the concept proposed by Blanchet-Bardon et al. that focal palmoplantar keratoderma with sensorineural hearing loss constitutes a distinct entity. In addition, the younger sister was affected with the CHILD syndrome. She suffered from linear ichthyosiform nevus with ipsilateral ectrodactyly. The simultaneous occurrence of the two syndromes is probably purely coincidental.
A case of inflammatory linear verrucous epidermal nevus (ILVEN) is reported. Short contact treatment with dithranol resulted in complete relief from itching and a remarkable clearing of all linear lesions except from a small verrucous band on the shin. In patients with ILVEN it is advisable to try dithranol therapy before carrying out surgical procedures such as excision, cryotherapy, electrocautery. The prompt response to dithranol is best explained by the assumption that most of the lesions in this case of ILVEN represented true linear psoriasis.
In a patient affected with acrodermatitis continua Hallopeau, acitretin (Ro 10-1670) monotherapy resulted in a complete clearance of pustulation at a dosage of 45 mg per day. At this dosage the leukotriene B4-induced intraepidermal accumulation of polymorphonuclear leukocytes was markedly inhibited.
A case of phacomatosis pigmentovascularis is reported. In order to explain the origin of this phenotype, we propose the genetic concept of twin spots. The teleangiectatic birthmark and the pigmentary naevus are caused by two different recessive mutations. Their loci are situated on the same chromosome. The embryo is doubly heterozygous, bearing one of the two mutations on one chromosome, whereas the other mutation is present on the homologous chromosome. During embryogenesis somatic crossing-over occurs, resulting in two different cell populations, each being homozygous for one of the two mutations. The mechanism of mitotic recombination would be a decisive event establishing an aetiological link between the two different naevi, thus making them twin spots.