Clearance of recalcitrant warts in a patient with idiopathic immune deficiency following administration of the quadrivalent human papillomavirus vaccine.

Human papillomavirus (HPV)-induced cutaneous warts are potentially serious and debilitating. In immunosuppressed patients, these warts may be resistant to standard therapies. We report a case of a young patient with a primary immune deficiency whose recalcitrant cutaneous warts regressed completely following administration of a quadrivalent HPV vaccine.

Pyoderma gangrenosum arising in a breast reduction scar: seven years post-procedure.

Pyoderma gangrenosum (PG) is an unusual skin condition causing inflammation and sterile ulceration. It may occur in the context of a systemic disease or in otherwise healthy patients following trauma. Treatment is immunosuppression. Surgical debridement may worsen the disease. Post-surgical PG of the breast is rare and in previous reports has occurred within days or weeks of surgery. We report a highly unusual case of PG occurring at an incision site seven years after reduction mammoplasty.

Acquired epidermodysplasia verruciformis due to multiple and unusual HPV infection among vertically-infected, HIV-positive adolescents in Zimbabwe.

BACKGROUND: We have previously described the presentation of epidermodysplasia verruciformis (EV)-like eruptions in almost a quarter of hospitalized adolescents with vertically-acquired human immunodeficiency virus (HIV) infection in Harare, Zimbabwe, a region with a high prevalence of HIV infection. METHODS: We performed a clinical case note review and skin biopsy from affected sites in 4 HIV-infected adolescents with EV-like lesions in Harare. Biopsies were processed for histology and for human papillomavirus (HPV) typing. RESULTS: All patients had long-standing skin lesions that pre-dated the diagnosis of HIV by several years. The histology of skin biopsies from all patients was consistent with EV. In each biopsy, EV-associated ß-HPV type 5 was identified (additionally, type 19 was found in 1 biopsy). Cutaneous wart-associated HPV types 1 and 2 were detected in all biopsies, together with genital lesion-associated HPV types 6, 16, and 52, (as well as ≥3 other genital lesion-associated HPV types). Despite immune reconstitution with combination antiretroviral therapy (cART), there was no improvement in EV-like lesions in any patient. CONCLUSIONS: EV is a disfiguring and potentially stigmatizing condition among this patient group and is difficult to treat; cART appears to have no impact on the progression of skin disease. Among adolescents with longstanding HIV-induced immunosuppression and with high levels of sun exposure, close dermatological surveillance for potential skin malignancy is required.

Prime-boost vaccination strategy in women with high-grade, noncervical anogenital intraepithelial neoplasia: clinical results from a multicenter phase II trial.

The objective of this study was to determine the clinical effectiveness of a prime-boost human papillomavirus (HPV) vaccine regimen. A nonrandomized phase II prime-boost vaccine trial was conducted. Women with biopsy-proven anogenital intraepithelial neoplasia (AGIN) 3 were vaccinated with three doses of a recombinant fusion protein comprising HPV 16, E6/E7/L2 (TA-CIN) followed by one dose of a recombinant vaccinia virus encoding HPV 16 and 18 E6/E7 (TA-HPV). Clinical responses were evaluated by serial photographs, symptomatology, and biopsies before and after vaccination. Twenty-nine women were vaccinated; 27 with vulval intraepithelial neoplasia 3 and 2 with vaginal intraepithelial neoplasia grade 3. Clinical responses were seen in five women (17%), with one complete and five partial responses. Fifteen women (62%) had symptomatic improvement. No serious adverse effects were recorded. This is the first trial of a prime-boost vaccination regimen using heterologous HPV vaccines (TA-CIN followed by TA-HPV) in the management of AGIN. Since the prime-boost approach in this cohort offered no significant advantages over single TA-HPV vaccination, there are no further studies planned using this protocol. Future studies are warranted to define responders to immunotherapy.

Pustular pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is an idiopathic inflammatory disease of unknown aetiology, frequently associated with an underlying systemic condition such as inflammatory bowel disease or haematological malignancy. Its occurrence tends to parallel exacerbations of the underlying disease. Four clinical variants of PG have been described and these include ulcerative, pustular, bullous and vegetative types. We report two cases of the pustular form, which is an uncommon variant of PG, where the pustules do not progress to form ulcers. Both our patients suffered with inflammatory bowel disease which remained quiescent as the pustular PG developed.

Guidelines for the management of cutaneous warts.

These guidelines for the management of cutaneous warts have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, and a brief overview of epidemiological aspects, diagnosis and investigation.

Treatment of verrucous carcinoma of vulva with acitretin.

We describe a 60-year-old patient with verrucous carcinoma of the vulva, which recurred 6 years after simple vulvectomy and radiotherapy. Treatment with acitretin led to significant improvement and ongoing disease control has been achieved with low-dose maintenance therapy of 10 mg acitretin daily.

Os acromiale in a baseball catcher.

Throwing injuries of the shoulder can result from an acute traumatic event or chronic overuse. Shoulder impingement has multiple etiologies; the most common being rotator cuff weakness/overuse and resultant glenohumeral instability. However, an uncommon cause of shoulder impingement syndrome is that of a nonfused os acromiale. There are three centers of ossification in the acromion which are usually completely fused by 18 yr of age. The most common site of nonunion is between the meso-acromion and meta-acromion. Os acromiale is reported at a rate of 14/1000 (1.4%) and is bilateral in approximately 62% of cases. The classic diagnosis is radiographically defined with both AP and axillary lateral views, and a contralateral comparison view may be helpful. Computerized axial tomography also aids in the diagnosis. Most os acromiale are asymptomatic. However, if recalcitrant impingement syndrome and/or rotator cuff tears are found in association with os acromiale, then surgical fusion or resection of the ossicle is recommended.

Allograft failure in cruciate ligament reconstruction. Follow-up evaluation of eighteen patients.

Previous authors have reported the efficacy of cruciate ligament allograft reconstruction of the knee suggesting that allograft strength is not significantly different than that of autografts. The purpose of this study was to elicit the cause of a higher-than-expected failure rate in cruciate ligament allograft reconstructions. After clinical diagnoses, 12 male and 6 female patients with cruciate ligament instability underwent intraarticular allograft reconstruction followed by an aggressive rehabilitation program. Deep-frozen, freeze-dried, ethylene oxide-sterilized, bone-patellar tendon-bone allografts were rehydrated, prestressed, and implanted by an open or arthroscopically assisted technique. Results revealed 6 of 18 failures. Knee instability, postoperative complications, and roentgenographic changes were evident. Evaluation of procurement technique showed that graft failure was significantly correlated with time to implantation. A significant difference in mean time from procurement and deep freezing to freeze-drying and sterilization between failed-versus-successful grafts was 265.5 +/- 61.9 versus 66.8 +/- 43.8 days, respectively. Total mean time of failed grafts from procurement to implantation was significantly greater (528.3 +/- 75.1 versus 207.3 +/- 53.1 days) than for successful grafts. All graft failures came from the same batch number. These findings indicate that cruciate ligament allograft reconstruction can be successful; however, longer shelf life negatively affects graft integrity.

Erythrodermic mycosis fungoides treated with total body irradiation and autologous bone marrow transplantation.

We describe a middle-aged man with aggressive erythrodermic mycosis fungoides whose responses to several well-established therapies for the disease were either poor or short-lived. Infusion of antibodies engineered against cells expressing the CD4 molecule produced little response. Total body irradiation coupled with autologous bone marrow transplantation led to an encouraging but unfortunately unsustained improvement.

Immunoelectron microscopical localization of human papillomavirus type 16 L1 and E4 proteins in cervical keratinocytes cultured in vivo.

The human papillomavirus (HPV) causes warts, but is also associated with the development of squamous cell dysplasia and carcinoma. The virus is host and tissue specific and the numerous HPV types show predilection for different body sites. Experimental production of HPV 16 particles is at present only possible using in vivo culture of keratinocytes containing episomal viral DNA. Using immunoelectron microscopy, we have investigated the localization of HPV 16 E4 and L1 proteins in a keratinized epithelium formed by grafting HPV 16-containing cervical keratinocytes onto the athymic mouse. New viral progeny are produced in this system, as confirmed by labeling of intranuclear particles with a mouse monoclonal antibody against the HPV 16 major capsid (L1) protein. The role of the E4 protein is not yet clear, although it is believed to be important for the later stages of the virus life cycle. Here we confirm its cytoplasmic localization in the cells of the spinous and granular layers and demonstrate co-localization with keratin tonofilaments.

A "public" T-helper epitope of the E7 transforming protein of human papillomavirus 16 provides cognate help for several E7 B-cell epitopes from cervical cancer-associated human papillomavirus genotypes.

We have identified a major T-cell epitope, amino acids 48-54 (DRAHYNI, in one-letter code) in the E7 open reading frame protein of human papillomavirus (HPV) type 16. Lymph node cells from mice immunized with synthetic peptides containing DRAHYNI proliferated and produced interleukin when challenged in vitro with peptide or whole HPV-16 E7 fusion protein. The T epitope was recognized in association with all five major histocompatibility complex class II I-A and I-E alleles tested. Synthetic peptides consisting of DRAHYNI linked to major B-cell epitopes on the E7 molecule formed immunogens capable of eliciting strong antibody responses to HPV-16 E7. The T epitope could provide help for the production of antibody to several B epitopes simultaneously, including a B epitope of HPV-18 E7 protein. Mice immunized with a peptide containing DRAHYNI and B epitope and, at a later date, infected with recombinant vaccinia E7 virus, displayed secondary antibody responses to E7. Because E7 has a role in cell transformation and is the most abundant viral protein in HPV-associated neoplastic cervical epithelial cells, the data have implications for vaccine strategies.