S. Jablonska

Cell-Mediated Immunity in Epidermodysplasia verruciformis

Investigations were performed in 6 cases of epidermodysplasia verruciformis and 2 healthy family members. Nonspecific cell-mediated immunity (CMI) was studied by measuring response to phytohemagglutinin (PHA) and concanavalin A (Con A), percentrages of E- and EAC-rosette-forming lymphocytes, bacterial skin tests, and allergic reactions to dinitrochloro-benzene (DNCB). Impairment of CMI was manifested by reduction in the percentage of E rosettes, and lowered response to PHA, and- to a lesser degree- to Con A. The immune response to DNCB sensitization was invariably negative. Impairment of CMI was greater in cases of long duration and with extensive lesions. The cases of similar duration and extent of lesions, which never showed tendency to tumor formation, were not different in CMI in comparison with cases with numerous tumors. Only in cases with very advanced tumors CMI was impaired parallel to the gravity of the patients general condition.

Twenty-one years of follow-up studies of familial epidermodysplasia verruciformis.

21 years of follow-up study of a family with epidermodysplasia verruciformis (e.v.) have shown that members of one family can be infected with different human papillomaviruses (HPVs), either HPV 3 or HPV 4, and sometimes with both. The clinical picture resembled disseminated flat warts in cases induced by HPV 3, whereas in those caused by HPV 4 there were flat red or red-brownish plaques and depigmented pityriasis versicolor-like lesions. Malignancies developed only in family members infected with HPV 4, whereas the cases due to HPV 3 ran a more benign and slowly progressive or stationary course. There were also abortive and regressive cases, and the 3 children in whom the wart-like lesions did not recur after removal had an unimpaired cell-mediated immunity (CMI). In all cases of e.v., irrespective of the inducing virus, CMI was low, which seems to be an important factor in the pathogenesis of the disease. Humoral antibodies directed specifically against HPV 3 were present in the majority of the cases, mainly those infected with HPV 3.

EVER2 Deficiency is Associated with Mild T-cell Abnormalities

Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by persistent flat warts or pityriasis versicolor-like lesions caused by betapapillomaviruses (EV-HPVs). Autosomal recessive EVER1 and EVER2 deficiencies account for EV in most patients. The mechanisms by which mutations in these partners of the Zinc transporter ZnT1 impair host defense against EV-HPVs are still poorly understood. Keratinocytes of EVER-deficient patients display an alteration of zinc homeostasis and an enhanced proliferative activity. Since EVER proteins are highly expressed in T lymphocytes, we aimed to assess the impact of EVER2 deficiency on T-cell development and function. We studied circulating lymphocyte populations in three adult EV patients sharing the same EVER2 mutation (T150fsX3). We found a normal count of CD4+ and CD8+ T cells and a normal proliferative capacity in response to anti-CD3 stimulation. However, we observed a significant increase of memory CD4+ and effector memory CD8+ T cells, a bias of the TCR Vαβ and Vγδ repertoires and an increase of skin-homing CD4+ T-cell subsets. Our findings suggest that EVER2-deficient patients display mild T-cell abnormalities. It remains unclear whether these abnormalities result from EVER deficiency, chronic EV-HPV infection, or both.

Specific Cell-Mediated Immunity in Patients with Epidermodysplasia verruciformis and Plane Warts

The characterization of different types of human papilloma viruses made it possible to study the specific immune responses to purified viral antigens in patients with warts. The specific cell-mediated immunity was investigated by means of a leukocyte migration inhibition factor test in 9 patients with epidermodysplasia verruciformis and 4 patients with regressing plane warts. The results show a significant increase in specific cell-mediated reactivity concomitant with the regression of the warts.

Langerhans Cells in Epidermodysplasia verruciformis

T cell defect and energy to contact sensitizers are characteristic of the depressed cell-mediated immunity in epidermodysplasia verruciformis (EV). In this disease the generalized infection with human papilloma viruses is associated with a high risk of skin cancers. Langerhans cell density was studied quantitatively in lesions and noninvolved epidermis of EV using OKT6 and anti-HLA-DR monoclonal antibodies with indirect immunofluorescence technique. No significant changes were found in apparently normal skin suggesting no primary defect of Langerhans cells in EV. A marked decrease in Langerhans cell number per unit of epidermal volume could be observed in EV lesions. This additional reduction of immunological surveillance at sites of potentially oncogenic human papilloma virus infection may contribute to the increased risk of malignant transformation in EV lesions.

Etretinate Therapy in Generalized Pustular Psoriasis (Zumbusch Type)

Etretinate therapy in 18 cases of generalized pustular psoriasis of the Zumbusch type proved to be effective and the therapy of choice. Only in 4 patients was maintenance therapy needed; in most cases relapses occurred after various intervals and patients responded invariably to reintroduction of the drug. Side-effects were slight. In 3 patients triglyceride levels became elevated, but only in 1 case the drug had to be withdrawn. In most of the patients generalized pustular eruption was accompanied, in some relapses or in some areas, by plaques of common psoriasis.

Virus-Like Tubular Cytoplasmic Inclusions in Epithelial Tumors

Electron microscopic studies were made in 11 cases of benign epithelial tumors (common warts, seborrheic warts, and papilloma) and malignant ones (Bowen’ disease and basal cell epithelioma). Characteristic tubular inclusions were detected chiefly in the cytoplasm of vascular endothelial cells in 6 cases (common warts, papilloma, Bowen’s disease, and basal cell epithelioma). Morphologically, they resembled paramyxoviruses and were exactly similar to those described in collagen diseases, chiefly in lupus erythematosus.

13-cis-retinoic acid and tetracycline versus 13-cis-retinoic acid alone in the treatment of nodulocystic acne

A comparative clinical study on therapy of nodulocystic acne with 13-cis-retinoic acid was performed in 32 patients. 20 patients were treated with a dose of 1 mg/kg body weight daily, and 12 with a combined therapy: 0.25 mg/kg/day 13-cis-retinoic acid and 0.5 g of tetracycline daily. In both groups the therapy was carried out for 16 weeks. The effect of the combined therapy within 4 months was favourable in 75% of the cases versus 100% in the group treated with larger doses of 13-cis-retinoic acid. Thus, the time needed for clearing was longer in some patients (up to 6 months). However, the incidence of side effects was considerably lower in the group of combined therapy. In acne fulminans 13-cis-retinoic acid alone is not effective and should be combined with corticosteroids.