Sławomir Obałek

Bowenoid papulosis of the male and female genitalia: Risk of cervical neoplasia

Sixteen patients with bowenoid papulosis (eleven male patients with bowenoid papulosis of the penis and five female patients with bowenoid papulosis of the vulva) were studied clinically, histologically, and virologically and followed up from 12 months to 5 years. In eleven of sixteen cases of bowenoid papulosis, molecular hybridization disclosed the presence of human papillomavirus type 16. In four cases we found new, not fully characterized human papillomavirus, and in two cases, we found both human papillomavirus 16 and new human papillomavirus (double infection). The mean age of male patients was 33 years and of female patients, 31 years. The mean duration of the disease was 2.4 and 3.6 years, respectively. The lesions cleared or did not recur in eight of eleven male patients after repeated partial excisions and in two of five female patients after conservative surgery. Cervical intraepithelial neoplasia (severe dysplasia) was present in three of five female patients, and human papillomavirus infection of the cervix was present in five of six sexual partners of male patients available for examination. Thus bowenoid papulosis presents a high risk for cervical neoplasia both for female patients and for sexual partners of male patients.

Natural cell-mediated cytotoxicity against various target cells in patients with epidermodysplasia verruciformis

Natural cell-mediated cytotoxicity of peripheral blood mononuclear cells was studied in eight patients with epidermodysplasia verruciformis induced by human papillomaviruses specific for epidermodysplasia verruciformis and in five patients with epidermodysplasia verruciformis-induced exclusively by human papillomavirus type 3. Nine patients with various cutaneous warts and 25 age- and sex-matched healthy persons were control subjects. Natural cell-mediated cytotoxicity against both K-562 erythroleukemic and Sk-v cells was in the normal range in patients with epidermodysplasia verruciformis induced by epidermodysplasia verruciformis-specific human papillomaviruses and in patients with cutaneous warts. The lysis of both targets, however, was significantly decreased in patients with the form of epidermodysplasia verruciformis associated with human papillomavirus type 3. Experiments with normal keratinocytes and with keratinocytes isolated from a malignant lesion bearing human papillomavirus type 5 genomes showed that the latter were susceptible to lysis by the peripheral blood mononuclear cells of healthy persons and of patients with cutaneous warts. Lysis of keratinocytes in epidermodysplasia verruciformis, however, was strongly reduced in patients with epidermodysplasia verruciformis induced by specific human papillomaviruses. This reduction was not associated with a decrease in anti-K-562 natural cell-mediated cytotoxicity. Our results suggest that in patients with epidermodysplasia verruciformis induced by disease-specific human papillomaviruses, there is reduced natural cell-mediated cytotoxicity against epidermodysplasia verruciformis keratinocytes.

T Cell Defect in Patients with Epidermodysplasia verruciformis due to Human Papillomavirus Type 3 and 5

Most of the patients with epidermodysplasia verruciformis (EV) were anergic to sensitization to dinitrochlorobenzene (DNCB) and were shown to have a decreased number of T lymphocytes and reduced lymphocyte PHA responsiveness. Preserved cell-mediated immunity (CMI) was found only in the abortive cases of EV infected with human papillomavirus type 3 (HPV-3). CMI was impaired to the same extent in patients with EV induced by HPV-3 and HPV-5, and in EV cases with combined infection with both viruses. In contrast to this, malignant transformation, i.e. of Bowens carcinoma type, was observed only in the 7 patients infected with HPV-5. This could indicate that malignancy in EV is related rather to the oncogenic potential of HPV-5 type than to the extent of T cell defect that was similar in both EV varieties due to HPV-3 and HPV-5.

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.

Immunological Studies in Psoriasis

Quantitative techniques of sensitization to 2,4-dinitrochlorobenzene (DNCB) was used to determine in psoriasis the intensity and frequency of allergic reactions to DNCB following primary challenge wit

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.

Comparative studies on cell-mediated immunity in patients with different warts.

The distribution of peripheral blood T and B lymphocytes, the in vitro lymphocyte response to PHA, and in vivo experimental DNCB sensitization were studied in patients with different clinical forms of warts (common, 84; flat, 88; plantar, 22; genital, 14) and in 15 cases of epidermodysplasia verruciformis (EV). The percentage of T lymphocytes forming E rosettes was significantly decreased in patients with common (54.8%), flat (47.5%) and plantar (58.3%) warts, and those with EV (47.6%) in comparison with normal controls (68.4%). The DNCB sensitivity developed less frequently and it was less intensive in patients with common and flat warts than in the normal population. 60% of EV cases were anergic to challenging doses of DNCB. The lymphocyte response to PHA was reduced in all groups of patients studied as compared to normals. T cell function was found to be most defective in patients with EV and those with flat warts. Only a slight but statistically significant defect was demonstrated in the common wart group. CMI in patients with both plantar and genital warts was shown to be almost normal; except minor alterations of PHA-induced lymphocyte transformation and E rosetting T lymphocyte counts. These data have shown the divergency of CMI defect in the patients with different clinical forms of warts caused by various HPV types. This could indicate that distinct HPV types varied in their infectiveness and host cell-mediated resistance is a fundamental factor preventing viral infection.

Continuous peritoneal dialysis for treatment of psoriasis

Psoriatic lesions were found to disappear spontaneously under haemodialysis [1 4] or continuous peritoneal dialysis [5] without any additional topical application of tar and corticosteroids, and/or systemic treatment with cytostatic drugs. Since both procedures recently introduced for therapy of psoriasis did not interfere directly with the excessive epidermal cell proliferation, a characteristic feature of the disease, the mechanism of the clearing of psoriatic lesions, remains completely unknown. Some hypotheses were raised such as removal of an noxious substance probably of epidermal origin which may be filtered by the normal kidney, but not excreted owing to tubular reabsorption in psoriasis [5], as well as immunological activation, inactivation of substances, or alteration of feedback systems [4]. Taking into consideration that lymphocytes and polymorphonuclear leucocytes [PMNL] may play an important rote in the pathogenesis of psoriasis, we decided to explore an alternative hypothesis that not elimination of low molecular dialysable factor, but removal of white blood cells with dialysate could be reponsible for the clearing of psoriasis. Lymphocytes and PMNL are known to form infiltrates in psoriatic lesions [ 6 7]. Furthermore, they could be a carrier of immunological factors, such as immune complexes, rheumatoid-like factors, anti-basal cell nuclei autoantibodies, or other immunoglobulins, and complement [8-9]. Complement activation products generated after binding of stratum corneum (SC) antigens with circulating anti-SC autoantibodies [t0] are presumed to exert chemotactic activity on PMNL which penetrate into the horny layer-forming Munro microabscesses [11]. Abnormalities of T-lymphocyte function were also reported [12]. The purpose of our paper was to determine : (1) whether white blood cells are removed by continuous peritoneal dialysis in a significant number, (2) whether some immunological factors related to these cells are eliminated on their surface

Lymphocyte transformation in mycosis fungoides

SummaryLymphocyte transformation tests with PHA were carried out in 26 patients with mycosis fungoides (MF) in different stages of the disease.In premycotic and infiltrative stages of MF there were no significant disturbances in the lymphocyte response to PHA.Inhibition of DNA synthesis and blastic transformation was observed only in the tumorous stage. The results are in favour of the nosological distinctiveness of mycosis fungoides within the lymphoma group.ZusammenfassungBei 26 Mycosis fungoides-Kranken wurde in den verschiedenen Krankheitsstadien ein Lymphocyten-Transformationstest mit PHA durchgeführt.Im prämykotischen und infiltrativen Stadium der MF gab es keine bedeutenden Störungen in der Lymphocyten-Reaktion auf PHA.Eine Inhibition der DNS-Synthese und blastische Transformation war nur in der Tumorperiode zu beobachten. Die Resultate sprechen für die nosologische Verschiedenheit der Mycosis fungoides in der Lymphomgruppe.

The morphology of butchers' warts as related to papillomavirus types

SummaryHand warts were studied in 160 butchers. Clinical and histological studies were performed in 190 warts and virological studies in 165 warts from 104 butchers. Since we found almost perfect correlation between the histological pattern and the type of infecting virus, it was possible to evaluate the virus types in a further 39 of 56 butchers without virological studies, on the basis of the histology of the warts. The most common infection was with HPV-2 (human papilloma virus) and HPV-7. Thirty-three butchers were infected with two types of viruses and three butchers with three HPVs. The morphology of warts varied considerably. The majority were similar to verrucae vulgares or verrucae planae. Some deep warts resembled myrmecia-type verrucae plantares. Often, several types of warts coexisted. Some clinical patterns were shown to be preferentially associated with distinct types of papillomaviruses: common warts with HPV-2, HPV-4, or HPV-7, plane and intermediate warts with HPV-3, HPV-10, HPV-28. HPV-7, previously identified for the first time in these butchers, was found to be associated with common warts or common wart-like, papillomatous lesions.