Marigdalia K. Ramirez-Fort

Coxsackievirus A6 associated hand, foot and mouth disease in adults: Clinical presentation and review of the literature

BACKGROUND Hand, foot, and mouth disease (HFMD) is generally considered a rare illness in adults. Classically, HFMD has been strongly associated with coxsackievirus strain A16 and enterovirus 71. The coxsackievirus A6 (CVA6) strain has been linked to severe worldwide outbreaks since 2008. CVA6 is associated with a more severe and profound course of disease, affecting both children and adults. OBJECTIVES To present a series of five adult patients diagnosed with HFMD due to CVA6. We investigate method of diagnosis and compare clinical presentation of adult cases to those in children. STUDY DESIGN Each patient underwent a full-body skin exam as well as inspection of the oral cavity. Rapid plasma reagin (RPR) and serologic assays by complement fixation against coxsackievirus B (1-6) and A (2,4,7,9,10,16) were performed as indicated. As standard serological testing does not detect CVA6, real-time reverse transcription-polymerase chain reaction (qRT-PCR) of serum, buccal swabs, and skin scrapings were performed by the Centers for Disease Control and Prevention (CDC). RESULTS Each patient had clinical findings consistent with various stages of HFMD. One patient presented with delayed onychomadesis and desquamation of the palms and soles. RPR and serologic assays by complement fixation against CVB (1-6) and CVA (2,4,7,9,10,16) were mostly negative, although elevated in two patients due to cross-reactivity. qRT-PCR identified CVA6 genetic material in samples from all patients. CONCLUSION This series demonstrates that there is a wide array of disease presentation of CVA6 associated HFMD in adults.

The biology of human papillomaviruses.

Human papillomaviruses (HPVs) are small, double-stranded DNA viruses that cause lesions in cutaneous and mucosal tissue and are responsible for carcinomas of the cervix, vagina, vulva and penis. HPVs sort into 5 genera with a total of approximately 150 species that have been sequenced. Its genome is comprised of an early (E) region encoding the viral regulatory proteins, a late (L) region encoding the viral structural proteins and a noncoding region that is essential to the viral life cycle. For infection to occur, the virus must access the basal epidermal layer where, following endocytosis and viral capsid disassembly, the L2 protein mediates viral genome transfer to the nuclei of mitotic keratinocytes. The viral genome is maintained in episomal form during the normal life cycle and replicates in synchrony with the host cell DNA under the mediation of E1, E2, E4 and E5 viral proteins. In most high-grade cervical neoplasms, however, the viral DNA is integrated into the host genome through the disruption of the E2 open reading frame. The oncoproteins E6 and E7, which were previously suppressed by E2, are then free to inhibit the Rb and p53 tumor suppressor pathways. The viral life cycle concludes with the packaging of the viral genome and virus release, which entails the E2-mediated recruitment of L2 to regions of replication, the expression of L1 and the assembly of the icosahedral capsid in the nucleus. Overall, the complex biology of HPV continues to be an important area of research with substantial implications for public health.

Zostavax: a subcutaneous vaccine for the prevention of herpes zoster

Introduction: Herpes zoster (HZ) occurs as a reactivation of dormant varicella zoster virus (VZV), and occurs more frequently in the aging population or the immunocompromised due to waning cell-mediated immunity. Up to 1 million cases of HZ are reported annually in the USA with an estimated 10 – 30% of the population being affected by shingles in their lifetime. HZ is a debilitating illness, and while mortality is low, morbidity remains a significant cause for concern with prevention efforts aimed at reducing VZV reactivation and its complications. The HZ vaccine was approved by the US Food and Drug Administration for individuals aged 50-years or older. However, the Center for Disease Control and Preventions Advisory Committee for Immunization Practices recommends the vaccine in individuals aged 60-years or older. Areas covered: Recent literature investigating the efficacy and indications of live attenuated zoster vaccine. Expert opinion: Live attenuated zoster vaccine is safe and efficacious in preventing HZ and decreasing the morbidity associated with postherpetic neuralgia. The vaccine is FDA approved in individuals aged 50-years or older but further studies are warranted to investigate the vaccines efficacy in immunosuppressed and immunocompromised patients.

Wax On, Wax Off: Pubic Hair Grooming and Potential Complications

Pubichairgrooming isbecomingan increasinglycommonpracticeamong women of all societies and demographic groups. In the United States, womenaremore likely togroomfor reasons that are sexuallydrivenand aremore likely to stopgroomingwhen lacking a current sexual partner. Further, pubic hair removal is significantly associated with a greater interest in sex and having a casual sex partner. Waxing is apopularepilation technique forpubichair removal,which involves applying hot wax to an area of skin that is then covered with muslin. The muslin is quickly removed, extracting the wax and unwanted hairs from the pubic area. Although relatively safe, waxing can cause microtrauma to the skin and its underlying structures with reported complications that include folliculitis, local spread of infection, burns, and syringoma development. Waxing-inducedfolliculitisofthepubicarea isacommoncomplication, usually secondary to infectionwithStaphylococcusaureus,Streptococcus pyogenes, orPseudomonasaeruginosa. The sourceof infectionmaybe normalskin flora,autoinoculation,contaminationofwaxingtools,orcolonizationof the individualperformingtheprocedure.Other infectionscan occur, andone reportdescribedawomanwithpoorly controlled insulindependent diabetesmellituswhodevelopedherpes simplex virus reactivationandsubsequentgroupAstreptococcustoxicshocksyndromefollowinga“Brazilian”bikiniwax.Anotherreportdescribedthedevelopment ofsyringomas in thegroin regionofa31-year-oldman,whichwasthought to be an inflammatory, hyperplastic response to repetitivewaxing. Pubichairwaxingcanalsocauseburns,withmostbeingsuperficialorpartialthicknessburns.Severeburnsrequiringdebridementandsplit skingrafting have been described following the use of self–waxing kits. Waxingcausesdeficits in themucocutaneousbarrier thatmaybesufficient for viral entry and transmission, potentially increasing the risk of acquiring sexually transmitted infections (STIs). One study demonstrated a correlation between sexually transmitted molluscum contagiosumand theuseof pubic hair removal practices. Still, there is a paucityofdataregardingtransmissionofotherviralagents, likelycomplicated bytheasymptomaticgenital sheddingofherpessimplexvirusesand long latency periods of human papillomaviruses. Becauseof itspopularity, healthpractitioners shouldbeawareof the potential dermatologic and systemic complications associatedwithpubic hairwaxing.While it has been shown that pubic hairwaxing directly correlates with increased sexual prevalence, more studies are necessary to further elucidate the risk of STI transmission after waxing. Individualswhowax their pubic hair shouldbe informedof this possible risk and perhaps be advised to abstain from sexual activity for a certain period of time after waxing.

Krokodil: From Russia With Love

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Management of cutaneous human papillomavirus infection in immunocompromised patients.

Individuals with inherited immunodeficiencies, autoimmune disorders, organ or bone marrow transplantation and with human immunodeficiency virus are particularly susceptible to developing severe, persistent and extensive manifestations of cutaneous human papillomavirus (HPV) disease. These complex cases require a unique and often multimodal approach to management. In this chapter, we discuss several states of immune compromise with increased susceptibility to HPV disease and review the literature on available management strategies including acitretin, cidofovir, Candida antigen, cimetidine, imiquimod, isotretinoin, fluorouracil, selenium, podophyllotoxin, photodynamic therapy, mammalian target of rapamycin inhibitors and the quadrivalent HPV vaccine.

Management of Cutaneous Human Papillomavirus Infection: Pharmacotherapies

A plethora of different treatment modalities for treating human papillomavirus (HPV) are available, offering a range of efficacies and balancing several patient needs. Here we discuss pharmacotherapies for HPV, focusing in particular on the mechanism of action and treatment efficacy. Immunomodulators such as Candida antigen, imiquimod and squaric acid stimulate cell-mediated immunity and induce production of antiviral cytokines. Proapoptotic and antiviral treatments such as podophyllin resin, podophyllotoxin gel, bleomycin, 5-fluorouracil, cidofovir and interferon α interfere with the viral reproduction cycle. Other therapies include trichloroacetic acid, acitretin, cantharidin and sinecatechins, some of which operate by epidermal destruction, effects on cellular proliferation and other mechanisms of which are poorly understood. Overall, given the high HPV recurrence rates, adjunctive use of antiviral agents should be considered in treatment, especially when managing severe or complicated presentations.

Remission of Refractory Benign Familial Chronic Pemphigus (Hailey-Hailey Disease) with the Addition of Systemic Cyclosporine

Background Benign chronic familial pemphigus (BFCP) is an autosomal dominant dermatosis characterized by flares of painful and often debilitating blistering lesions in high friction areas of the body such as the groin, axillae, lateral neck, and intergluteal cleft. Limited knowledge of its pathophysiology has made treatment of BFCP a considerable challenge and efficacy with current first line therapies, topical corticosteroids and antibiotics, is variable. Case Report We present a case of this disease in a 52 year old woman that has responded dramatically to the addition of oral cyclosporine to her existing regimen of oral acitretin, with significant improvement of skin lesions, mobility, and quality of life. Cyclosporines mechanism of action in BFCP is poorly understood, although it possibly acts through inhibition of proinflammatory cytokines in keratinocytes or modulation of intracellular calcium. BFCP, the use of cyclosporine for its treatment, and possible mechanisms of action of cyclosporine are reviewed.

Adjuvant Narrow Band UVB Improves the Efficacy of Oral Azithromycin for the Treatment of Moderate to Severe Inflammatory Facial Acne Vulgaris.

Background: Acne vulgaris (AV) is a common inflammatory disease of the pilosebaceous unit. A variety of treatment modalities are available for the treatment of AV. Among the available options, oral azithromycin is popularly prescribed for its proven anti-inflammatory effects. Narrow band UVB (NBUVB) also has a potent anti-inflammatory action. Concomitant use of both modalities may result in a synergistic therapeutic response; however, the combined efficacy has not yet been evaluated for the treatment of inflammatory AV. Objective: The aim of this study was to compare the efficacy of oral azithromycin plus NBUVB (peak 311 nm) to oral azithromycin alone for the treatment of moderate to severe inflammatory AV. Materials and Methods: A randomized, open-label, clinical trial was conducted over 4 weeks. Subjects were randomized into two groups. Group 1 received 500 mg of oral azithromycin three times per week. Group 2 received 500 mg of oral azithromycin plus NBUVB three and two times per week, respectively. Concomitant topical or oral AV treatments were not permitted during the treatment period. Response to treatment was measured by photographic records at the primary endpoint (2 weeks) and at the end of treatment. Results: One hundred and four subjects were enrolled in the trial; 94 subjects completed the treatment period of the study. Group 2 demonstrated significant clinical improvement of the inflammatory papular lesions (88.55%) compared with group 1 (70.34%) at the end of treatment (P = 0.002). The clinical response of pustular (P = 0.562), nodular (P = 0.711) and cystic (P = 0.682) lesions did not significantly differ between the two treatment groups. Interestingly, response to treatment in group 2 had a significant anatomical predilection for the forehead (P = 0.023). There was no side-effect except erythema, which subsided within 1-2 days. Conclusion: NBUVB plus oral azithromycin is more effective than oral azithromycin alone for treating papular lesions of inflammatory AV. NBUVB is certainly a viable adjunct in acne therapy.

Analysis of Trial Data for Infliximab and Golimumab: Baseline C‐Reactive Protein Level and Prediction of Therapeutic Response in Patients With Psoriatic Arthritis

Anti–tumor necrosis factor medications have demonstrated good efficacy in treating psoriatic arthritis (PsA). Clinical responses at the primary end point in recent clinical trials of golimumab in PsA subjects yielded lower American College of Rheumatology 20% criteria for improvement (ACR20) responses than those seen in the Infliximab Multinational Psoriatic Arthritis Controlled Trial 2 infliximab study. However, baseline C‐reactive protein (CRP) levels of PsA subjects enrolled in these trials differed significantly. We hypothesized that baseline CRP levels predict the observed differing clinical response rates at the primary end point.