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.

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.

Topical salicylic acid gel as a treatment for molluscum contagiosum in children.

OBJECTIVE: To determine if the application of salicylic acid gel or phenol solution affected resolution of molluscum contagiosum (MC) lesions in children. PATIENTS AND METHODS: This was a randomized, prospective controlled trial with two treatment arms and one vehicle arm for treatment of MC in children. The trial was set in the dermatology outpatient clinics of a teaching hospital and a district general hospital. A total of 114 children were enrolled in the study (age range 1-15 years) over a 4-year period; 83 of the children completed the study. Patients were randomized to receive one of three possible treatments: monthly vehicle application of 70% alcohol, monthly application of 10% phenol in 70% alcohol once or twice weekly 12% salicylic acid gel. All patients also received treatment with daily aqueous cream to reduce eczema. They returned monthly to the clinic for treatment and counting of MC lesions. They were reviewed either until complete resolution or up to 6 months, whichever occurred sooner. The main outcome measure was the time taken for complete resolution of MC lesions. RESULTS: In the intention-to-treat analysis there was no difference between treatment arms when the 31 non-completers were analysed as failures (log-rank test: p = 0.38). In an 'as treated' analysis, 16 of 27 children (59.2%: 95% confidence interval 30.2-88.3) had cleared with vehicle, 18 of 32 (56.3%, 30.3-82.2) with phenol solution and 21 of 24 (87.5%, 50.1-124.9) with salicylic acid gel (log-rank test: p = 0.03). On an as treated basis, salicylic acid was significantly better at clearing MC than dilute phenol (p = 0.006). The treatment in all groups was very well tolerated or acceptable in 93% of children. CONCLUSION: Our results suggest that topical salicylic acid may be beneficial in speeding resolution of MC in children. Dilute phenol application does not appear to affect the disease course.

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.

Stress fractures in the athlete. Diagnosis and management.

Stress fractures can be a troublesome injury for the sports medicine clinician. The first description was in military personnel, but recently there is an increasing awareness and diagnosis of stress fractures in the athletic population. Stress fractures have been described in all extremities. Some fractures appear to have a degree of sports specificity. Bone is a dynamic tissue which strengthens and remodels in response to stress. Maladaptation to stress causes osteoclastic activity to supersede osteoblastic activity, thereby allowing weakening of the bone. These areas of weakening may fracture and create prodromal symptoms and clinical findings. Localised pains of insidious onset which are activity related are the hallmarks in the clinical history. The physical examination can exhibit localised tenderness, redness and swelling. Radiographs can be negative for up to 4 months. The gold standard for diagnosis is the triple phase 99mtechnetium bone scan. The treatment of a stress fracture is usually conservative. Very few cases require surgical management. The algorithm of conservative management includes: rest, appropriate education for treatment and preventive care, analgesics, serial radiographs, icing and physical therapy modalities, appropriate exercise to prevent detraining, rehabilitation and a regimented return to participation and competition.

An unusual stress fracture in a multiple sport athlete.

Most overuse injuries are a direct result of repetitive stresses which may create a condition of maltraining. Young athletes are no exception to this rule. Swimming and baseball both create stresses to the humerus which may result in injuries to the shoulder and upper extremity. Stress fractures (fatigue fractures) are usually limited to the lower extremity (i.e., tibia or metatarsal). Upper extremity stress fractures, especially of the humerus, are very uncommon. Precipitating factors include repetitive stresses, low grade external forces, rapid application of muscular force to the bone, or an underlying disease or pathologic weakness of the bone. The majority of these fractures are primarily due to abnormal and repetitive stresses to bones. This case study examines the mechanism of injury, clinical presentation, and treatment of a clinically apparent stress fracture which ultimately converted to an overt humerus fracture in a 14-yr-old cross-trained athlete.

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.

Delayed treatment of a malreduced distal femoral epiphyseal plate fracture.

Fractures of the epiphyseal plate are considered rare when compared with the more prevalent injuries found in competitive sports, but the complications associated with this type of trauma are a major concern. The factors affecting the success or failure of healing include the severity of injury, patient age, and the type and expedience of treatment. This case study examines the clinical presentation and treatment of a 15-yr-old high school football player who sustained a displaced, distal femoral epiphyseal Salter II fracture. Primary treatment consisted of nonmanipulative, nonweight bearing knee immobilization. The treatment resulted in malunion, pain, decreased range of motion and physical deformity; therefore, the patient sought a second opinion. On physical exam, the displacement and rotational deformity of the fracture site were unacceptable. The fracture was treated 20 days post-injury via open reduction with internal fixation. On follow-up, the athlete demonstrated radiographic healing, normal physical exam, and no significant leg length discrepancy or deformity. The athlete successfully returned to full competitive sport activity.

Postural responses to lateral perturbation in healthy subjects and ankle sprain patients.

The purpose of this study was to investigate postural responses of healthy subjects and patients with recent ankle sprains following a perturbation that created sway in the frontal plane. EMG data were taken from the posterior tibialis (PT) (not monitored in patients), peroneal longus (PL), and tibialis anterior muscles (TA). Subjects stood on a platform that provided a rotational perturbation (approximately 70 degrees.s-1) in the frontal plane. This perturbation had the effect of everting and loading one limb while inverting and unloading the contralateral limb. An initial response in the PT of the loaded limb and the PL of the unloaded limb was noted at approximately 50 ms following the perturbation. This was followed by a bilateral response in the TA at 60 ms. The amplitude of the TA muscle was significantly greater in the loaded limb. For ankle sprain patients a bilateral TA response and a PL response in the unloaded limb was noted at approximately 65 ms. TA response amplitude ratios between the loaded and unloaded limbs were similar to that of the healthy subjects. These data suggest that ankle sprain patients use a modified postural response following lateral perturbation as a compensation for the injury.

False negative bone scan in a female runner.

Stress fractures are more prevalent in today's fitness cognizant society. Stress fractures of the femoral neck are common and present with specific symptoms and findings. The diagnosis is based on clinical history, physical exam, radiography, bone scintigraphy, and computed tomography (C.T.) scans. The triple-phase bone scan is the most sensitive test for the diagnosis of stress fractures and is considered the gold standard for the diagnosis of the occult stress fracture. This case presents a 42-yr-old female marathon runner who presented with hip pain and clinical symptoms indicating a stress fracture of the femoral neck. Initial radiographs and a triple-phase bone scan were negative. When symptoms persisted, a repeat x-ray revealed a femoral neck fracture of the superior surface. In spite of a false negative bone scan, clinical suspicion allowed appropriate treatment of this femoral neck stress fracture. Nondiagnosed stress fractures of the femoral neck may lead to severe disability, including avascular necrosis of the femoral head. Therefore, clinical index of suspicion is very important even if ancillary tests are nondiagnostic.

Local treatments for cutaneous warts.

BACKGROUND: Viral warts caused by the human papilloma virus represent one of the most common diseases of the skin. Any area of skin can be affected although the hands and feet are by far the commonest sites. A very wide range of local treatments are available. OBJECTIVES: To assess the effects of different local treatments for cutaneous, non-genital warts in healthy people. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (January 2003), the Skin Group trials register (January 2003), MEDLINE (1966 to January 2003), EMBASE (1980 to January 2003) and a number of other key biomedical and health economics databases. In addition the cited references of all trials identified and key review articles were searched. Pharmaceutical companies involved in local treatments for warts and experts in the field were contacted. The most recent searches were carried SELECTION CRITERIA: Randomised controlled trials of local treatments for cutaneous non-genital viral warts in immunocompetent human hosts were included. DATA COLLECTION AND ANALYSIS: Study selection and assessment of methodological quality were carried out by two independent reviewers. MAIN RESULTS: Fifty two trials were identified which fulfilled the criteria for inclusion in the review. The evidence provided by these studies was generally weak because of poor methodology and reporting. In 17 trials with placebo groups that used participants as the unit of analysis the average cure rate of placebo preparations was 30% (range 0 to 73%) after an average period of 10 weeks (range 4 to 24 weeks). The best available evidence was for simple topical treatments containing salicylic acid, which are clearly better than placebo. Data pooled from six placebo-controlled trials show a cure rate of 144/191 (75%) compared with 89/185 (48%) in controls, odds ratio 3.91 (95% confidence interval 2.40 to 6.36), random effects model. Most of the bigger trials of cryotherapy studied different regimens rather than comparing cryotherapy with other treatments or placebo. Pooled data from two small trials that included cryotherapy and placebo or no treatment, showed no significant difference in cure rates. In two trials comparing cryotherapy with salicylic acid and one comparing duct tape with cryotherapy no significant difference in efficacy was demonstrated. There was no consistent evidence for the effectiveness of intralesional bleomycin. Four studies, using warts rather than individuals as the unit of analysis, had widely varying results which could not be meaningfully pooled. There was some evidence for the efficacy of dinitrochlorobenzene, a potent contact sensitizer. Pooled data from two small studies comparing dinitrochlorobenzene with placebo showed cure rates of 32/40 (80%) and 15/40 (38%) respectively, odds ratio 6.67 (95% confidence interval 2.44 to 18.23), random effects model. Only limited evidence was found for the efficacy of topical 5-fluorouracil, intralesional interferons and photodynamic therapy.Bleomycin, dinitrochlorobenzene, 5-fluorouracil, interferons and photodynamic therapy are potentially hazardous or toxic treatments. REVIEWER'S CONCLUSIONS: There is a considerable lack of evidence on which to base the rational use of the local treatments for common warts. The reviewed trials are highly variable in method and quality. Cure rates with placebo preparations are variable but nevertheless considerable. There is certainly evidence that simple topical treatments containing salicylic acid have a therapeutic effect. There is less evidence for the efficacy of cryotherapy and some evidence that it is only of equivalent efficacy to simpler, safer treatments. Dinitrochlorobenzene appears to be effective but there were no statistically significant differences when compared with the safer, simpler and cheaper topical treatments containing salicylic acid. The benefits and risks of 5-fluorouracil, bleomycin, interferons and photodynamic therapy remain to be determined.

Local treatments for cutaneous warts.

BACKGROUND: Viral warts caused by the human papilloma virus represent one of the most common diseases of the skin. Any area of skin can be affected although the hands and feet are by far the commonest sites. A very wide range of local treatments are available. OBJECTIVES: To assess the effects of different local treatments for cutaneous, non-genital warts in healthy people. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (March 1999), the Skin Group trials register (March 1999), MEDLINE (1966 to August 2000), EMBASE (1980 to August 2000) and a number of other key biomedical and health economics databases. In addition the cited references of all trials identified and key review articles were searched. Pharmaceutical companies involved in local treatments for warts and experts in the field were contacted. SELECTION CRITERIA: Randomized controlled trials of local treatments for cutaneous non-genital viral warts in immunocompetent human hosts were included. DATA COLLECTION AND ANALYSIS: Study selection and assessment of methodological quality were carried out by two independent reviewers. MAIN RESULTS: Forty-nine trials were identified which fulfilled the criteria for inclusion in the review. The evidence provided by these studies was generally weak because of poor methodology and reporting. In 17 trials with placebo groups that used participants as the unit of analysis the average cure rate of placebo preparations was 30% (range 0 to 73%) after an average period of 10 weeks (range 4 to 24 weeks). The best available evidence was for simple topical treatments containing salicylic acid, which are clearly better than placebo. Data pooled from six placebo-controlled trials show a cure rate of 144/191 (75%) compared with 89/185 (48%) in controls, odds ratio 3.91 (95% confidence interval 2.40 to 6.36), random effects model. Most of the bigger trials of cryotherapy studied different regimens rather than comparing cryotherapy with other treatments or placebo. Pooled data from two small trials that included cryotherapy and placebo or no treatment, showed no significant difference in cure rates. In two other trials comparing cryotherapy with salicylic acid no significant difference in efficacy was demonstrated. There was no consistent evidence for the effectiveness of intralesional bleomycin. Four studies, using warts rather than individuals as the unit of analysis, had widely varying results which could not be meaningfully pooled. There was some evidence for the efficacy of dinitrochlorobenzene, a potent contact sensitizer. Pooled data from two small studies comparing dinitrochlorobenzene with placebo showed cure rates of 32/40 (80%) and 17/40 (43%) respectively, odds ratio 5.42 (95% confidence interval 1.99 to 14.75), random effects model. Only limited evidence was found for the efficacy of topical 5-fluorouracil, intralesional interferons and photodynamic therapy. Bleomycin, dinitrochlorobenzene, 5-fluorouracil, interferons and photodynamic therapy are potentially hazardous or toxic treatments. REVIEWER'S CONCLUSIONS: There is a considerable lack of evidence on which to base the rational use of the local treatments for common warts. The reviewed trials are highly variable in method and quality. Cure rates with placebo preparations are variable but nevertheless considerable. There is certainly evidence that simple topical treatments containing salicylic acid have a therapeutic effect. There is less evidence for the efficacy of cryotherapy and no convincing evidence that it is any more effective than simple topical treatments. Dinitrochlorobenzene appears to be effective but no more so than the safer, simpler and cheaper topical treatments containing salicylic acid. The benefits and risks of 5-fluorouracil, bleomycin, interferons and photodynamic therapy remain to be determined.

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.