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Background: Local hyperthermia has been demonstrated to be a safe and efficacious treatment for warts. Objective: We aimed to evaluate the safety and efficacy of an epicutaneous heat patch to induce local hyperthermia for the treatment of warts. Methods: We performed an uncontrolled, proof of concept study by applying a novel, reproducible, epicutaneous heat patch to a target wart for 2 hours per day for 12 weeks. There were 15 evaluable participants. An untreated wart was also observed and measured. Wart measurements included the diameter in two dimensions, an investigator global assessment (IGA) score, wart clearance, and monitoring for adverse events as endpoints at week 12 (end of treatment) and week 24 (end of study). Results: No major adverse events were observed. 6.7% of participants reported minor cutaneous events. At week 24, 46.7% of participants achieved complete clearance of both warts. Limitations: The small sample size and lack of independent control in each participant were the main limiting factors. Conclusion: Local hyperthermia delivered by epicutaneous heat patches was well-tolerated, safe, and achieved complete clearance in both treated as well untreated warts in 46.7% of participants at week 24 after 12 weeks of daily use. Clinicaltrials.gov: NCT01746056 J Drugs Dermatol. 2019;18(4):368-373.

Birt-Hogg-Dubé syndrome (BHDS) is an uncommon autosomal dominant genodermatosis characterized by a triad of skin tumors--fibrofolliculomas, trichodiscomas, and acrochordons--together with an increased risk of renal tumors and spontaneous pneumothoraces. This report describes multiple facial angiofibromas as the predominant initial manifestation of BHDS. The patient had a total of 41 facial papules removed via shave excision, initially for diagnostic and then for therapeutic purposes; histologic evaluation revealed diagnostic features of angiofibroma in 39 lesions and fibrofolliculoma in only 2. BHDS should be considered, along with tuberous sclerosis and multiple endocrine neoplasia type 1, in the differential diagnosis of multiple facial angiofibromas, particularly when onset is in adulthood.

Prior studies have identified local heat therapy as a treatment for recalcitrant warts. We have employed a thermal pad that raises local temperature to 42-43ºC for at least 2 hours in a proof of concept study of three patients with recalcitrant warts. The recalcitrant warts cleared in all three patients beginning in the fourth and fifth weeks after daily treatment with the pads. There were no adverse events. We conclude that the timing of clearance following use of these thermal pads is likely via direct viral killing and immunologic mechanisms. Further controlled trials are underway.

Papillomaviruses are a family of nonenveloped DNA viruses that infect the skin or mucosa of their vertebrate hosts. The viral life cycle is closely tied to the differentiation of infected keratinocytes. Papillomavirus virions are released into the environment through a process known as desquamation, in which keratinocytes lose structural integrity prior to being shed from the surface of the skin. During this process, virions are exposed to an increasingly oxidative environment, leading to their stabilization through the formation of disulfide cross-links between neighboring molecules of the major capsid protein, L1. We used time-lapse cryo-electron microscopy and image analysis to study the maturation of HPV16 capsids assembled in mammalian cells and exposed to an oxidizing environment after cell lysis. Initially, the virion is a loosely connected procapsid that, under in vitro conditions, condenses over several hours into the more familiar 60-nm-diameter papillomavirus capsid. In this process, the procapsid shrinks by ~5% in diameter, its pentameric capsomers change in structure (most markedly in the axial region), and the interaction surfaces between adjacent capsomers are consolidated. A C175S mutant that cannot achieve normal inter-L1 disulfide cross-links shows maturation-related shrinkage but does not achieve the fully condensed 60-nm form. Pseudoatomic modeling based on a 9-Å resolution reconstruction of fully mature capsids revealed C-terminal disulfide-stabilized “suspended bridges” that form intercapsomeric cross-links. The data suggest a model in which procapsids exist in a range of dynamic intermediates that can be locked into increasingly mature configurations by disulfide cross-linking, possibly through a Brownian ratchet mechanism., IMPORTANCE Human papillomaviruses (HPVs) cause nearly all cases of cervical cancer, a major fraction of cancers of the penis, vagina/vulva, anus, and tonsils, and genital and nongenital warts. HPV types associated with a high risk of cancer, such as HPV16, are generally transmitted via sexual contact. The nonenveloped virion of HPVs shows a high degree of stability, allowing the virus to persist in an infectious form in environmental fomites. In this study, we used cryo-electron microscopy to elucidate the structure of the HPV16 capsid at different stages of maturation. The fully mature capsid adopts a rigid, highly regular structure stabilized by intermolecular disulfide bonds. The availability of a pseudoatomic model of the fully mature HPV16 virion should help guide understanding of antibody responses elicited by HPV capsid-based vaccines.

background Hyperthermia therapy Was described previously to be effective for treating warts using a hot water technique as We as an ultrasound hyperthermia technique. Recently, two other papers described controlled localized heat therapy for cutaneous warts. A new heat-generated application system and method has been developed for treating warts using a self-administered, self-adhesive disposable exothermic patch. objective The objective of this study was to describe our clinical experience in using the exothermic patch to successfully treat patients with cutaneous recalcitrant warts who failed to respond to multiple antiwart therapy. method Two patients with recalcitrant warts that did not respond to other therapeutic modalities were treated with the exothermic patch with complete remission of their warts. Exothermic patches were used in this study that were specially constructed to provide long-lasting, continuous, and reproducible heating of the skin surface for at least 2 hours at a temperature level of 42–43°C, which will not burn or otherwise injure the skin. conclusion Warts are difficult to treat in part because there are no specific anti-Papillomavirus drugs or methods available. We describe our clinical experience in successfully treating two patients with recalcitrant warts using the exothermic patch.

background : An elderly woman with B-cell lymphoma confined to the skin of the lower extremity was treated with combination chemotherapy and radiation therapy. She relapsed with new skin lesions outside the original radiation port that responded to additional radiation therapy and remains in remission 12 months after her last treatment. objective : This article investigates the diagnosis, treatment, and prognosis of primary cutaneous B-cell lymphoma. methods : The relevant literature was researched through computer data bases and bibliographies. results : Patients who present with localized lesions of primary cutaneous B-cell lymphoma have a favorable prognosis regardless of the type of therapy, although relapses may occur in the absence of systemic disease. conclusion : Vie advocate the use of local therapies as initial treatment in patients with localized primary cutaneous B-cell lymphoma. J Dermatol Surg Oncol 1992;18:951–954.

REPORT OF A CASE A 38-year-old white man was involved in an automobile accident in 1967 with resulting damage to the T-10 vertebrae and chronic pain. Two years ago, the patient bought a chair with an electric vibrator and a heater cushion to ease his lower back pain. He started using it every night for a few hours while watching television. One month after starting the device, an eruption developed on his lower back. The eruption was sometimes accompanied by crusted areas on the location where the heater and vibrator touched his skin. Figure 1 shows the diffuse, blue-to-purple erythematous reticulated eruption, with hyperpigmentation of the lower back without vesicles or hyperkeratosis. A 3-mm punch biopsy specimen was obtained from this area. Histologic findings are demonstrated in Fig 2. What is your diagnosis? DIAGNOSIS: Erythema ab igne. DISCUSSION Erythema ab igne, otherwise known as toasted skin syndrome, 1,2 is a persistent macular erythema and hyperpigmentation occurring in a

The viral DNA sequences in mouse C127 cells transformed by bovine papillomavirus type 1 (BPV-1) virions, by full-length linear BPV-1 DNA, or by a defined transforming subgenomic DNA segment of BPV-1 were examined by reassociation kinetics and blot hybridization. In all cases, the transformed cells contained multiple copies of BPV-1 DNA, present exclusively as supercoiled or nicked circular extrachromosomal molecules or as a slowly migrating complex of circular viral DNA molecules. In the transformed cell lines established from cells transfected with full-length linear BPV-1 DNA, there was recircularization of the input DNA which in some cases resulted in the loss of the restriction site used in the linearization of the DNA. In the transformed cell lines established with the defined subgenomic segment there was circularization of the DNA accompanied by the acquisition of new sequences or duplication and rearrangement of the BPV-1 sequences. In contrast to other well-studied virus transformation systems, no integration of the BPV-1 genome into the host chromosome could be detected under conditions sensitive enough to detect 0.1-0.2 viral genome equivalent. It was concluded that maintenance of transformation may be mediated by nonintegrated viral DNA.

We have studied tumorigenic transformation of mouse tissue culture cells by bovine papillomavirus (BPV) as a model of papillomavirus-induced cell proliferation. When BPV or its 7.9-kb full-length viral DNA genome induces focal transformation of mouse calls, the viral DNA is maintained in the transformed cells as multiple extrachromosomal copies. The transforming capacity was initially localized to a 69% subgenomic fragment of the viral DNA genome. We have further characterized the BPV DNA sequences that can encode the transforming function by generating and analyzing the transforming activity of a series of BPV DNA deletion mutants. The results indicated that two discontinuous segments of the viral DNA are required for transformation. One segment, near the 5' end of the 69% transforming fragment, probably represents a control element of the viral DNA. The second segment, which lies within the 3' end of the 69% fragment, encodes transforming sequences of the viral DNA. A retroviral control element (the long terminal repeat DNA. A retroviral control element (the long terminal repeat DNA of Harvey murine sarcoma virus) will activate the 2.3-kb segment at the 3' end of the 69% fragment to transform the mouse cells.

The effect of mouse L-cell interferon on bovine papillomavirus type 1 (BPV-1) transformation of murine cells was examined. Mouse interferon reduced the level of BPV-1-induced transformation of mouse C127 cells by 95%. Long-term treatment of established BPV-1-transformed mouse cell clones with mouse L-cell interferon led to a decrease in the average number of the plasmid viral genomes present in these cells to 1/3 to 1/8. Although revertant lines could not be isolated from these lines in the absence of treatment with interferon, flat revertants were easily selected from two independent clonal transformed lines carried for 60 generations in the continued presence of 200 units of interferon per ml. These flat revertants had the biological characteristics of nontransformed C127 cells and could be retransformed by BPV-1. Southern blot hybridization failed to detect BPV-1 DNA in any of eight independent revertant lines examined under conditions that could detect 0.2 copies per cell. We conclude that interferon treatment has resulted in a selective reduction of the amount of extrachromosomal BPV-1 DNA in transformed cells and has cured some treated cells completely of their viral DNA.

The susceptibility of human papillomavirus infection to polyclonal human leukocyte interferon (IFN-alpha) has been evaluated in patients with epidermodysplasia verruciformis (EV), a disease with extensive chronic papillomavirus-induced warts. In a double-blind, placebo-controlled study with intralesional IFN-alpha, four of five IFN-alpha-treated warts regressed; none of the placebo-treated warts responded (p = 0.024). Three patients with EV were treated with systemic IFN-alpha for 4 weeks in an open study, achieving partial regression of warts in all three. In a double-blind, placebo-controlled study, warts in two children with EV regressed with systemic IFN-alpha while two who received placebo showed no improvement. The lesions recurred following cessation of therapy. At the completion of therapy with IFN-alpha, histologic normalization was accompanied by a 95% decrease in the number of viral antigen-containing cells in the warts (p less than 0.001). We conclude that warts in EV respond to systemic and intralesional IFN-alpha.

In ten patients with gyrate atrophy (GA) and hyperornithinemia, the head hair was fine, straight, and sparse. On microscopic examination, both scalp and pubic hair contained intermittent dark cores within the medullary zone, which was not a deposit, but appeared to be due to the unusual refractive properties of loosely formed macrofilaments amidst wide spaces containing a structureless electron lucent but compact substance, which was insoluble in both water and solvents. Seven of the ten patients had abnormal wave forms on electroencephalography. Three of the five patients who underwent muscle biopsy had tubular aggregates. Of particular interest was the toxicity of exogenous ornithine added to muscle cell culture from GA patients as compared with the lack of toxicity in muscle from control patients. What specific role the hyperornithinemia and absence of OAT is playing in the histopathology of hair and muscle and the EEG changes awaits further biochemical investigation.

The papillomaviruses, which are widely distributed in nature, typically induce benign skin tumours (warts) in their natural hosts (reviewed in ref. 1). These viruses are members of the papovavirus group, as are the polyomaviruses2. In contrast to polyomaviruses such as SV40, polyoma and BK (reviewed in ref. 3), the papillomaviruses have not been extensively studied, primarily because of the lack of a suitable tissue culture system. In general, the proliferative skin changes induced by the papillomaviruses are limited to the epidermal cells, and the viruses have a very narrow host range. However, some bovine papilloma viruses (BPV) are exceptional in that they induce fibropapillomas in their natural host (cows); these BPV can also induce cellular transformation in tissue culture4–6 and fibroblastic tumours in heterologous animals, including hamsters7, mice5 and horses8,9. BPV DNA from virions can also transform rodent cells and is tumorigenic in hamsters10. Recently, a tissue culture focus assay11 in mouse cells (NIH 3T3 and C127) has been described for those BPV which are the aetiological agents of fibropapillomas in cows. The virally transformed cells, which did not contain infectious virus, grew in soft agar and were tumorigenic in nude (nu/nu) mice. We12 have recently molecularly cloned the entire genomes of BPV-1 and BPV-2 (ref. 13) in Escherichia coli K12 using the certified plasmid vector pBR322 (ref. 14). We now demonstrate that these cloned DNAs can transform NIH 3T3 and C127 cells. Further, a molecularly cloned fragment which contains 69% of the BPV-1 genome can also induce cellular transformation.

Mouse L cell interferon reduced the level of bovine papillomavirus (BPV-1) induced transformation of mouse C127 cells approximately 20-fold. Continued treatment of established BPV-1 transformed mouse cells with mouse L cell interferon lead to a reduction in the copy number of the plasmid viral genomes present in these transformed cells. Flat revertants were selected from two independent transformed lines carried 60 generations in the presence of 200 units/ml of interferon. These flat revertants had the biologic characteristics of their untransformed parent C127 cells which included low cell saturation density and the inability to form colonies in soft agar. The revertants could be retransformed by BPV and each of 8 different revertant lines examined was found to be “cured” of their viral DNA sequences as determined by Southern blot hybridization.

A quantitative tissue culture assay for bovine papilloma virus (BPV) has been developed. Extracts of bovine papillomas which contained either BPV-1 or BPV-2 induced distinct foci in two mouse cell lines (NIH 3T3 and C127). Focus formation followed single-hit kinetics, suggesting that a single particle was required for focus induction. Preincubation of extracts with rabbit anti-BPV-1 serum neutralized their infectivity. The morphologically transformed cells contained BPV DNA sequences, grew in low serum and in soft agar, and were tumorigenic for nude mice.

A car mechanic sustained a deep partial thickness burn of the wrist when his metal watch strap short circuited the battery of a car upon which he was working.

† We describe a family with typical epidermodysplasia verruciformis (EV) in which only male members are affected. Whereas none of the index patient's ten children have EV, four of eight grandsons born to his daughters have inherited the disorder. All are infected with human papillomavirus (HPV) 3 and HPV 8. The inheritance in this kindred most likely results from an X-linked recessive genetic defect. Since other kindreds have been described with autosomal inheritance, this novel inheritance pattern suggests that the persistent high clinical susceptibility to HPV infection characteristic of EV may result from defects in either of at least two different genetic loci, one of which may be located on the X chromosome. (Arch Dermatol1985;121:864-868)

Idiopathic calcinosis of the scrotum, which is a rarely reported condition of unknown etiology, may be easily misdiagnosed as epidermal or pilar cysts. Histologically, the diagnosis is easy and quite typical. Report of a Case A 24-year-old man was admitted to The Chaim Sheba Medical Center in November 1975 for removal of several asymptomatic scrotal cysts of several years' duration. Examination showed several firm, non-tender nodules of various sizes on the scrotum; the larger nodules were apparently formed from several smaller ones joined together (Fig 1). The diagnosis of epidermal cysts was made and all visible lesions were surgically removed. During surgery, some of the lesions were found to contain a viscous, thick, white-yellowish fluid. None contained an obvious sac. Postoperative recovery was uneventful. Results of the following laboratory tests were found to be either within normal limits or negative: complete blood count, ESR, routine urinalysis, VDRL, blood glucose, blood

• A 49-year-old man was found to have a rare, mutilating basal cell epithelioma of the face. Conventional early therapy with surgery and radiotherapy did not halt the progress of the disease in a hospital environment. The patient died 12 years later. ( Arch Dermatol 114:239-240, 1978)