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Risankizumab is approved for treatment of moderate to severe plaque psoriasis. Availability of a patient-controlled single self-injection of risankizumab may improve adherence and long-term management of psoriasis.To investigate efficacy, safety, and usability of a new risankizumab 150 mg/mL formulation administered as a single subcutaneous injection via prefilled syringe (PFS) or autoinjector (AI).Efficacy, safety, usability, and acceptability of risankizumab 150 mg/mL PFS or AI were investigated in adults with moderate to severe psoriasis in two phase 3 studies. Study 1 was a multicenter, randomized, double-blinded, placebo-controlled study that investigated 150 mg/mL risankizumab PFS; study 2 was a multicenter, single-arm, open-label study that investigated 150 mg/mL risankizumab AI.At week 16, risankizumab 150 mg/mL demonstrated efficacy vs. placebo (Psoriasis Area and Severity Index ≥90% improvement (PASI 90), 62.9% vs. 3.8%; static Physician Global Assessment (sPGA) 0/1, 78.1% vs. 9.6%; bothThe efficacy, safety, and usability of 150 mg/mL risankizumab delivered as a single PFS or AI injection support use of this new formulation in patients with moderate to severe plaque psoriasis.NCT03875482 and NCT0387508.

Anomalous coronary arteries are rare and often incidental findings. Most variants are benign. We present the case of a 75-year-old man with exertional dyspnea in whom the left anterior descending coronary artery arose from the right sinus of Valsalva, and the left circumflex coronary artery originated from the distal right coronary artery and supplied the obtuse marginal branch. No arteries originated from the left sinus of Valsalva. The patient was prescribed optimal medical therapy for atherosclerotic stenosis in his ramus intermedius. His symptoms were stable 3 years later.

Capsule summary (33 of 35 words; 2 of 2 sentences): Secukinumab reduced the inflammation and the expression of ACE2, which encodes the SARS-CoV-2 receptor, in plaques of patients with psoriasis. Reductions in ACE2 expression with secukinumab significantly correlated with reductions in disease activity.

This prospective, parallel-group, randomized, double-blind, multicenter study compared the efficacy and safety of FV-100 with valacyclovir for reducing pain associated with acute herpes zoster (HZ). Patients, ≥50 years of age, diagnosed with HZ within 72 h of lesion appearance who had HZ-associated pain, were randomized 1:1:1 to a 7-day course of either FV-100 200 mg QD (n = 117), FV-100 400 mg QD (n = 116), or valacyclovir 1000 mg TID (n =117). Efficacy was evaluated on the basis of the burden of illness (BOI; Zoster Brief Pain Inventory scores); incidence and duration of clinically significant pain (CSP); pain scores; incidence and severity of post-herpetic neuralgia (PHN); and times to full lesion crusting and to lesion healing. Safety was evaluated on the basis of adverse event (AE)/SAE profiles, changes in laboratory and vital signs values, and results of electrocardiograms. The burden of illness scores for pain through 30 days were 114.5, 110.3, and 118.0 for FV-100 200 mg, FV-100 400 mg, and valacyclovir 3000 mg, respectively. The incidences of PHN at 90 days for FV-100 200 mg, FV-100 400 mg, and valacyclovir 3000 mg were 17.8%, 12.4%, and 20.2%, respectively. Adverse event and SAE profiles of the two FV-100 and the valacyclovir groups were similar and no untoward signals or trends were evident. These results demonstrate a potential for FV-100 as an antiviral for the treatment of shingles that could both reduce the pain burden of the acute episode and reduce the incidence of PHN compared with available treatments.

not available.

Background: Genital herpes and herpes labialis are prevalent, physically and pychologically painful, and often disabling. Herpes zoster is often very painful and may result in months or years of postherpetic neuralgia (PHN). Over the past two decades, the treatment of these conditions has been transformed by guanosine nucleoside antivirals such as valacyclovir (Valtrex®), a highly bioavailable prodrug of acyclovir (Zovirax®), and famciclovir (Famvir®), a highly bioavailable prodrug of penciclovir (Denavir®). Objective: We describe the pharmacology, pharmacokinetics, and clinical efficacy of valacyclovir for the treatment of herpes simplex, herpes zoster, and other viral infections. Valacyclovir is also compared with acyclovir and famciclovir. Methods: All published literature containing the word “valacyclovir” was reviewed and summarized. Results: Valacyclovir is the only oral antiviral agent approved for therapy of herpes labialis, the only antiviral drug approved for a 3-day course in the episodic treatment of recurrent genital herpes, as well as the only antiviral drug approved for once daily dosing for suppressive therapy. In herpes zoster, valacyclovir is more effective than acyclovir and equally effective as famciclovir at hastening the healing of zoster-associated pain and PHN. Conclusion: Valacyclovir is safe and effective in the therapy of patients with herpes simplex and herpes zoster and may be useful in other viral infections.

Vaccines against infectious diseases have been available since the 1800s, when an immunization strategy against smallpox developed by Jenner gained wide acceptance. Until recently, the only vaccination strategies available involved the use of protein-based, whole killed, and attenuated live virus vaccines. These strategies have led to the development of effective vaccines against a variety of diseases with primary or prominent cutaneous manifestations. Effective and safe vaccines now used worldwide include those directed against measles and rubella (now commonly used together with a mumps vaccine as the trivalent MMR), chickenpox, and hepatitis B. The eradication of naturally occurring smallpox remains one of the greatest successes in the history of modern medicine, but stockpiles of live smallpox exist in the United States and Russia. Renewed interest in the smallpox vaccine reflects concerns about a possible bioterrorist threat using this virus. Yellow fever is a hemorrhagic virus endemic to tropical areas of South America and Africa. An effective vaccine for this virus has existed since 1937, and it is used widely in endemic areas of South America, and to a lesser extent in Africa. This vaccine is recommended once every 10 years for people who are traveling to endemic areas. Advances in immunology have led to a greater understanding of immune system function in viral diseases. Progress in genetics and molecular biology has allowed researchers to design vaccines with novel mechanisms of action (eg, DNA, vector, and VLP vaccines). Vaccines have also been designed to specifically target particular viral components, allowing for stimulation of various arms of the immune system as desired. Ongoing research shows promise in prophylactic and therapeutic vaccination for viral infections with cutaneous manifestations. Further studies are necessary before vaccines for HSV, HPV, and HIV become commercially available.

Herpes genitalis is one of the most common viral sexually transmitted diseases in the world, with an estimated seroprevalence in the US of greater than 20%. Two viruses of the same family cause herpes genitalis: herpes simplex virus 1 and 2. After the resolution of primary infection, the virus persists in the nerve roots of the sacral plexus, often causing recurrent (though generally less severe) outbreaks. These outbreaks, as well as the infectious potential to the patient's sexual partners, results in significant psychological stress on the patient, and has a tremendous negative impact on QOL. Current treatment modalities may result in a reduction in the number of outbreaks and viral shedding, but no cure exists. Although studies have clearly demonstrated the negative impact of recurrent genital herpes on QOL, an assessment scale specific to herpes was not developed until recently. Earlier studies indicated that patients did not perceive a significant benefit from episodic treatment with antivirals, but studies using the Recurrent Genital Herpes Quality of Life Questionnaire (RGHQoL) have now demonstrated that suppressive antiviral therapy improves quality of life in patients with frequent recurrences of genital herpes. However, not all patients with recurrent genital herpes need suppressive therapy, and proposed factors to consider include frequency of recurrence, physical and psychological distress caused by recurrences, and the potential for transmission to the patient's sexual partner. Newer therapeutic modalities, including the topical immune response modifier resiquimod and herpes vaccines, may eventually be shown to further decrease the psychological morbidity of recurrent genital herpes.

An increased understanding of the pathogenesis and transmission of HSV infections and the development of sensitive type-specific diagnostic tests have helped develop effective prophylactic and therapeutic antiviral drug regimens. Effective medications have been available for quite some time, but the most optimal regimens are still under investigation. Advances in the treatment of atypical presentations of HSV infection (such as the use of cidofovir gel for the treatment of acyclovir-resistant HSV) are promising. Newer treatments, such as resiquimod, actually may alter the course of HSV infection, reducing the severity and frequency of recurrences. Vaccines are being explored as preventive and therapeutic measures against HSV.

Human papillomavirus infection remains a great source of morbidity and mortality. Progress in understanding the structure of HPV and its pathogenesis has led to a wide variety of possible new treatment modalities to combat HPV-related disease. Most HPV infections (whether high risk or low risk) resolve without any medical intervention. Persistent or progressive disease, however, remains difficult to treat. Although currently available therapies have proved efficacious and tolerable in the treatment of nongenital and genital warts, no single therapy is uniformly effective in eradicating persistent HPV infection. Cytodestructive methods, such as cryotherapy, remain the primary treatment modality for nongenital warts. Immune response modifiers, such as imiquimod, currently show the greatest promise in treating HPV-induced anogenital lesions, both with respect to complete response and in preventing recurrence. Human papillomavirus infection is one of the most common sexually transmitted diseases in the world, and cervical cancer still causes significant morbidity and mortality. Pap smear tests have greatly reduced the incidence and mortality of cervical cancer in developed countries. Additional research will focus on primary and secondary prevention strategies. Vaccines against high-risk HPV types are promising modalities currently under investigation to prevent HPV infections and possibly to treat them.

Herpes simplex virus persists in a latent form for the life of its host, periodically reactivating and often resulting in significant psychosocial distress for the patient. Currently no cure is available. Antiviral therapy is the main treatment modality, used either orally, intravenously, or topically to prohibit further replication of the virus and thereby minimize cellular destruction. However, immunologic advances in the treatment and prevention of herpes simplex infections are promising and continue to be studied.

Antecedents: Les personnes de 50 ans et plus ont non seulement un risque accru de contracter le zona, mais elles sont aussi plus susceptibles de developper la morbidite a long terme que constitue l'algie postzosterienne. L'algie postzosterienne est la douleur qui persiste une fois que l'eruption du zona a disparu. Elle frappe au moins 40% des patients atteints de zona et plus de 75% de ceux âges de plus de 75 ans, ce qui en fait l'affection neurologique la plus frequente chez les personnes âgees. Objectif: evaluer les interventions therapeutiques pouvant attenuer ou meme supprimer l'algie postzosterienne. Il n'y a pas un seul traitement qui a ete efficace de facon constante dans ce cas. Il semble que la meilleure facon d'aborder le traitement soit l'administration d'un antiviral des le debut de la maladie. Les etudes en cours sur le zona visent a mettre au point des traitements preventifs utilisant le vaccin antivaricelleux pour reduire davantage les symptomes de l'algie postzosterienne ou les supprimer. Conclusion: La meilleure maniere d'attenuer les symptomes de l'algie postzosterienne, c'est d'administrer des antiviraux des les premieres manifestations du zona; les autres classes de medicament sont tres peu efficaces darts le traitement de l'algie postzosterienne qui s'est installee. L'utilisation generalisee du vaccin antivaricelleux peut aider a reduire davantage l'algie postzosterienne dans un avenir eloigne.

Background: Human papillomaviruses (HPV) are common human pathogens and are classified into more than 80 different types. These viruses produce benign warts in many cases and aggressive squamous cell carcinomas in other cases. Objective: The goal of this review is to update the reader on the epidemiology, pathogenesis, and therapy of HPV infections. Nonanogenital warts are transmitted by skin-to-skin contact while anogenital warts are usually transmitted sexually. Both types of warts produce much morbidity but rarely undergo malignant transformation. They are commonly treated with surgical or cytodestructive therapy, but immunomodulatory agents, such as imiquimod, have been proven to be very effective in anogenital warts and are being evaluated in nonanogenital warts. Other types of HPV have marked oncogenic potential such that over 99% of all cervical cancers and over 50% of other anogenital cancers are due to infection with oncogenic HPV. Many cofactors, such as cigarette smoking, genetics, and helper viruses, have potential roles in HPV oncogenesis, but their relative contributions are poorly understood. Other control measures for warts and HPV-associated cancers are under study, but the greatest future potential may be from the development of prophylactic and therapeutic vaccines. Conclusions: Infection with HPV is very prevalent as are the clinical manifestations of this family of pathogens. Improved therapies for warts (e.g., imiquimod) have recently become available. Vaccines for HPV offer hope for future interventions for warts as well as for prevention of anogenital malignancies.

Objective Bromovinyl-uracil (BVU) is the principal metabolite of sorivudine, a potent anti-zoster nucleoside. BVU binds to, and irreversibly inhibits, the enzyme dihydropyrimidine dehydrogenase (DPD). The objective of this study was to assess the time course of recovery of DPD activity after oral administration of sorivudine in patients with herpes zoster and to correlate restoration of DPD activity and levels of uracil with the elimination of sorivudine and its metabolite BVU from the circulation. Methods Sorivudine was given orally as 40 mg once-daily doses for 10 consecutive days to a total of 19 patients with herpes zoster. Serum sorivudine, BVU, and circulating uracil and DPD activity in peripheral blood mononuclear cells (PBMCs) were determined before, during, and after administration of sorivudine. Results BVU was eliminated from the circulation within 7 days after the last sorivudine dose. DPD activity in PBMCs, which was completely suppressed in 18 of the 19 subjects and markedly suppressed in the remaining subject during administration of sorivudine, recovered to baseline levels within 19 days after the last dose of sorivudine in all subjects and within 14 days in all but one of the subjects. The restoration of DPD activity was temporally associated with elimination of BVU from the circulation. The elevated uracil concentrations produced by inhibition of DPD activity fell rapidly after cessation of sorivudine administration and also were temporally associated with elimination of BVU from the circulation. The time course of recovery of DPD activity in three patients with renal impairment was similar to that of the other subjects. Conclusions This study indicates that sorivudine therapy is associated with a profound depression of DPD activity. Recovery of DPD activity occurred within 4 weeks of the completion of sorivudine therapy, which indicates that fluorinated pyrimidines may be safely administered 4 weeks after completion of sorivudine therapy. Clinical Pharmacology & Therapeutics (1997) 61, 563–573; doi

Famciclovir is the well-absorbed oral form of penciclovir, an antiviral agent with potent activity against varicella-zoster virus (VZV) and herpes simplex virus (HSV-1) and 2 (HSV-2). After oral administration, famciclovir is rapidly converted to penciclovir with a bioavailability of 77%. penciclovir is efficiently phosphorylated to the active metabolite, penciclovir-triphosphate, and has a prolonged intracellular half-life of approximately 9-10 h in VZV-infected cells, and 10 and 20 h in cells infected with HSV-1 and HSV-2, respectively. Two multicenter clinical trials have shown that famciclovir given during the acute zoster phase accelerated healing of cutaneous lesions. More importantly, in a placebo-controlled study, famciclovir reduced the duration of postherpetic neuralgia (PHN), particularly in elderly patients. Famciclovir has also been proven effective in treating recurrent genital herpes, as demonstrated by a reduction in times to cessation of viral shedding, complete healing, and loss of all symptoms. One study showed that suppressive therapy with famciclovir was effective in reducing genital herpes episodes in patients with frequent recurrences. A promising new area of investigation for famciclovir is controlling virus replication in patients with chronic hepatitis B virus (HBV) or HBV reinfections after liver transplant. Results from a double-blind, placebo-controlled, pilot study and several case reports have shown that famciclovir, alone or in combination with other agents, decreased HBV-DNA levels and was tolerated with long-term treatment. Available clinical data indicate that famciclovir is an effective agent for treating herpes and holds significant promise for the treatment of chronic HBV infection HBV reinfection after liver transplantation.

Although herpes zoster (shingles) can occur in anyone with a history of chickenpox, it is more prevalent and usually more severe in older patients (i.e. persons over 50 years of age). While the cutaneous manifestations of shingles usually resolve in approximately 4 weeks, the pain can persist for several months, or even years in the untreated patient. This pain following healing of the skin, termed post-herpetic neuralgia (PHN), can be very severe. Three well tolerated and effective antiviral drugs are available for the therapy of acute herpes zoster. The nucleoside analogues, aciclovir, famciclovir and valaciclovir, appear to shorten the duration of PHN to a similar degree, but none affects the incidence of PHN. Aciclovir is taken 5 times daily for 7 days, while famciclovir is taken 3 times daily for 7 days. Valaciclovir, the L-valyl ester of aciclovir, when taken orally, produces plasma levels of aciclovir equivalent to those seen following intravenous administration of aciclovir. Valaciclovir has not only been proved to be more efficient than aciclovir (i.e. 3 times daily administration) but also more effective than aciclovir in shortening the duration of PHN. Current studies are determining the relative efficacy of valaciclovir versus famciclovir. Presently, a fourth drug, sorivudine, is being compared with aciclovir for the therapy of acute herpes zoster in older patients, but data from these trials are not yet available. Corticosteroids have been used to treat herpes zoster for much longer than the antiviral drugs, but the effect of corticosteroids on PHN does not appear to be consistent. Corticosteroids plus aciclovir did not provide an added benefit over aciclovir alone in one study but this combination did appear to improve the quality of life of older patients in another investigation. The recent availability of the varicella zoster vaccine may cause shingles to be an uncommon and/or mild disease by the mid twenty-first century. Meanwhile, the search continues for more effective and efficient therapies for acute herpes zoster with the primary goal in older patients to affect the most important sequela of zoster in this population, PHN.

Infection with the human immunodeficiency virus (HIV) leads to a chronic disarmament of the immune system. The process is progressive, having different manifestations as the status of the immune system slowly deteriorates. Some of the most common manifestations of HIV infection are cutaneous in origin, and they can have infectious, neoplastic, or noninfectious or non-neoplastic etiologies. A brief history of HIV is given, and the most common cutaneous presentations of the virus infection of interest to podiatrists are outlined.

† A 65-year-old woman presented with cutaneous, pruritic papules of the upper part of her chest. Histologic findings and culture of a biopsy specimen confirmed that these papules were caused by an infection with Prototheca wickerhamii , an achloric alga that rarely infects humans. Natural killer cell activity in this patient was significantly depressed before initiation of therapy. Reevaluation following successful treatment with oral tetracycline hydrochloride and topical amphotericin B cream revealed an improvement in natural killer cell activity. This patient is presented to demonstrate a rare clinical presentation of protothecosis; to document that cutaneous protothecosis can be successfully treated without the risk of toxic side effects associated with systemic antifungal agents; and to illustrate that although most patients with cutaneous protothecosis are immunosuppressed, infection with this alga appears to be at least partially responsible for the immunosuppression. ( Arch Dermatol. 1989;125:1249-1252)

To the Editor.— Several reports support the belief that patients with cutaneous T-cell lymphoma (CTCL) have a potential for developing second lymphoid malignancies. 1 Fewer reports have documented the association of CTCL with epidermal malignancies such as squamous cell carcinoma. 2 Only two patients have been reported to have CTCL associated with malignant melanoma. 3 We now report the third patient having both of these latter two malignancies. Report of a Case.— A 60-year-old man presented to the Dermatology Center at the University of Alabama in Birmingham in June 1984 due to exacerbation of an asymptomatic eruption that had been present 15 years without treatment. He also reported the recent development of swelling in his groin. He denied any malaise or weight loss. His medical history was otherwise significant only for hypothyroidism treated with levothyroxine sodium. Physical examination revealed erythematous, poikilodermatous patches and indurated plaques and nodules on both lower

† Bullous lesions associated with Vibrio vulnificus infection developed in two patients, both of whom had hepatic cirrhosis. One patient had a recent history of ingestion of raw oysters, while the other patient had recently exposed skin lacerations to sea water. Both patients died within 24 hours of hospitalization, in spite of antibiotic treatment. Vibrio vulnificus was isolated from blood and bullae in both patients. Histologic examination of skin biopsy specimens revealed epidermal/ dermal separation and clusters of bacteria within dermal vessels with a negligible inflammatory response. ( Arch Dermatol 1986;122:818-820)

• An elderly man presented with bright red-to-purple confluent nodules and plaques of the scalp that appeared clinically consistent with angiosarcoma. He had undergone surgical removal of a similar lesion from his left temple seven months before this presentation. Although routine histologic examination was not sufficient for diagnosis, Merkel cell carcinoma was diagnosed by immunohistochemical studies and electron microscopy. In addition, oat cell carcinoma of the lung was excluded with a computed tomographic scan of his chest. With chemotherapy, the recurrent and metastatic lesions of Merkel cell carcinoma completely resolved, rapidly recurred, and resolved a second time with chemotherapy. Eight months following the fourth course of chemotherapy, the patient again developed widespread cutaneous lesions. He committed suicide within one month of this last recurrence. An autopsy revealed no primary tumor other than of the skin. (Arch Dermatol1987;123:1368-1370)

To the Editor.— Cutaneous T-cell lymphoma (CTCL, mycosis fungoides) is a malignant neoplasm of helper T cells that may be protean in its clinical expression. Verrucous lesions are among the rarest of its morphological appearances and, as such, may be easily clinically confused with many nonmalignant conditions, including common warts and deep fungal infections, unless carefully examined histologically. This case report describes a patient who developed a widespread verrucous form of CTCL with extensive systemic involvement, which was demonstrated by the findings of bladder biopsy, thoracentesis, blood studies, and computed tomography, and who subsequently died of systemic lymphoma. Report of a Case.— In October 1986, a 29-year-old man was admitted to the Veterans Administration Medical Center, Birmingham, Ala, for gross hematuria. At that time, he was seen in dermatologic consultation for multiple verrucous lesions of his trunk and extremities. His medical history was remarkable for the diagnosis, by skin biopsy