Christopher Downing

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.

Systematic review of interleukin-12, interleukin-17, and interleukin-23 pathway inhibitors for the treatment of moderate-to-severe chronic plaque psoriasis: ustekinumab, briakinumab, tildrakizumab, guselkumab, secukinumab, ixekizumab, and brodalumab.

Background: Monoclonal antibodies known as biologic agents specifically targeted against interleukin-12 (IL-12), interleukin-17A (IL-17), and interleukin-23 (IL-23) have been the focus of research for moderate-to-severe chronic plaque psoriasis in recent years. Objectives: To discuss the immune-mediated model of psoriasis and to summarize current knowledge of the clinical efficacy and safety of new biologic agents for moderate-to-severe chronic plaque psoriasis. Methods: The PubMed database was searched for relevant articles on ustekinumab, briakinumab, tildrakizumab (MK-322), guselkumab, secukinumab, ixekizumab, and brodalumab published between January 2005 and July 2013. Results: Fifty-five articles were identified. These studies suggest that the biologic agents specifically targeting IL-12, IL-17, and IL-23 are efficacious and safe in the treatment of moderate-to-severe psoriasis in adults. Conclusion: Current data from clinical trials suggest that biologic agents targeting IL-12, IL-17, and IL-23 are safe and efficacious drugs for use in moderate-to-severe chronic plaque psoriasis. Long-term data still need to be established.

Safety and Efficacy Data on Vaccines and Immunization to Human Papillomavirus.

Since the discovery of the causal association between human papillomavirus (HPV) and cervical cancer, efforts to develop an effective prophylactic vaccine to prevent high-risk HPV infections have been at the forefront of modern medical research. HPV causes 530,000 cervical cancer cases worldwide, which is the second most common cause of cancer deaths in women; a worldwide collaboration among epidemiologists, molecular biologists, vaccinologists, virologists, and clinicians helped lead to the development of two highly effective prophylactive HPV vaccines. The first, Gardasil, is a quadrivalent vaccine made up of recombinant HPV L1 capsid proteins from the two high-risk HPV types (16/18) responsible for 70% of cervical cancer cases as well as two low-risk HPV types (6/11) which are the causative agent for genital warts. The second, Cervarix, is a bivalent vaccine that was FDA approved three years after Gardasil and is also composed of L1 capsid proteins from HPV types 16/18. This review article focuses on the safety and efficacy data of both FDA-approved vaccines, as well as highlighting a few advances in future HPV vaccines that show promise in becoming additional treatment options for this worldwide disease.

Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients

Non-melanoma skin cancers represent a major cause of morbidity after organ transplantation. Squamous cell carcinomas (SCC) are the most common cutaneous malignancies seen in this population, with a 65–100 fold greater incidence in organ transplant recipients compared to the general population. In recent years, human papillomaviruses (HPV) of the beta genus have been implicated in the pathogenesis of post-transplant SCCs. The underlying mechanism of carcinogenesis has been attributed to the E6 and E7 proteins of HPV. Specific immunosuppressive medications, such as the calcineurin inhibitors and azathioprine, are associated with a higher incidence of post-transplant SCCs compared to other immunosuppressive agents. Compared to other immunosuppressives, mTOR inhibitors and mycophenolate mofetil have been associated with a decreased risk of developing post-transplant non-melanoma skin cancers. As a result, they may represent ideal immunosuppressive medications in organ transplant recipients. Treatment options for post-transplant SCCs include surgical excision, Mohs micrographic surgery, systemic retinoid therapy, adjunct topical therapy, electrodessication and curettage, and radiation therapy. This review will discuss the epidemiology, risk factors, and management options of post-transplant SCCs. In addition, the underlying mechanisms of beta-HPV mediated carcinogenesis will be discussed.

HPV Carcinomas in Immunocompromised Patients.

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide and can result in pre-malignancies or overt malignancies of the skin and mucosal surfaces. HPV-related illnesses are an important personal and public health problem causing physical, mental, sexual and financial detriments. Moreover, this set of malignancies severely affects the immunosuppressed population, particularly HIV-positive patients and organ-transplant recipients. There is growing incidence of HPV-associated anogenital malignancies as well as a decrease in the average age of affected patients, likely related to the rising number of high-risk individuals. Squamous cell carcinoma is the most common type of HPV-related malignancy. Current treatment options for HPV infection and subsequent disease manifestations include imiquimod, retinoids, intralesional bleomycin, and cidofovir; however, primary prevention with HPV vaccination remains the most effective strategy. This review will discuss anogenital lesions in immunocompromised patients, cutaneous warts at nongenital sites, the association of HPV with skin cancer in immunocompromised patients, warts and carcinomas in organ-transplant patients, HIV-positive patients with HPV infections, and the management of cutaneous disease in the immunocompromised patient.

Advancements in Pharmacotherapy for Noncancerous Manifestations of HPV

Human papillomavirus (HPV) is the most common sexually transmitted disease. Via infection of the basal epithelial cells, HPV causes numerous malignancies and noncancerous cutaneous manifestations. Noncancerous cutaneous manifestations of HPV, including common, plantar, plane, and anogenital warts, are among the most common reasons for an office visit. Although there are various therapies available, they are notoriously difficult to treat. HPV treatments can be grouped into destructive (cantharidin, salicylic acid), virucidal (cidofovir, interferon-α), antimitotic (bleomycin, podophyllotoxin, 5-fluorouracil), immunotherapy (Candida antigen, contact allergen immunotherapy, imiquimod) or miscellaneous (trichloroacetic acid, polyphenon E). The mechanism of action, recent efficacy data, safety profile and recommended regimen for each of these treatment modalities is discussed.

Deep Fungal Infections, Blastomycosis-Like Pyoderma, and Granulomatous Sexually Transmitted Infections

Granulomatous diseases are caused by multiple infectious and noninfectious causes. Deep fungal infections can present in the skin or extracutaneously, most commonly with lung manifestations. An Azole or amphotericin B is the universal treatment. Blastomycosis-like pyoderma is a clinically similar condition, which is caused by a combination of hypersensitivity and immunosuppression. Successful treatment has been reported with antibiotics and, more recently, the vitamin A analog, acitretin. Granuloma inguinale and lymphogranuloma venereum cause ulcerative genital lesions with a granulomatous appearance on histology. The Centers for Disease Control and Prevention recommens treatment of these genital infections with doxycycline.

Current and emerging drugs for acute bacterial skin and skin structure infections: an update.

Introduction: Antibiotic resistance, the emergence of multidrug-resistant bacteria and the exponential rise of methicillin-resistant Staphylococcus aureus (MRSA) acute bacterial skin and skin structure infections (ABSSSI) pose a great threat to the public health. In order to combat these threats, development of new antibiotics is vital and measures to decrease antibiotic resistance should be prioritized. Areas covered: This manuscript provides an overview of the current FDA-approved antibiotics and the antibiotics in development for MRSA ABSSSI. Expert opinion: A great need exists currently for novel antibiotics to combat multidrug-resistant MRSA. As clinicians, it is imperative to implement proper management in order to reduce antibiotic resistance.

Acyclovir Lauriad®: a muco-adhesive buccal tablet for the treatment of recurrent herpes labialis

The treatment of recurrent herpes labialis remains a challenge in the 21st century. The virus is ubiquitous and there is no vaccine against the disease. Although recurrence episodes are usually of shorter duration than the primary episode, they are debilitating to patients and there is significant stigma associated with the disease. Acyclovir Lauriad® is a new topical agent that was approved by the US FDA in 2013 for the treatment of recurrent herpes labialis, which affects approximately 20–40% of the population worldwide. The drug is a muco-adhesive tablet, applied to the upper gum at the onset of prodromal symptoms. Utilizing Lauriad® technology, a biologically active compound traverses the mucous membrane to deliver a high concentration of acyclovir directly to the site of the herpes simplex virus infection. Data from a Phase III clinical trial shows that this may be a promising therapy for patients with recurrent herpes labialis.

Blistering Distal Dactylitis in an Adult

Background: Blistering distal dactylitis is a localised infection of the anterior pad of the distal phalanx of the digits. It most commonly affects children and uncommonly adults with a history of immunosuppression or trauma. Objective: A case of blistering distal dactylitis in a 32-year-old male is reported. The patient was not immunocompromised and did not report trauma. Conclusion: Blistering distal dactylitis may rarely present in adults (including those who are not immunocompromised or reporting trauma) and thus should be in the differential diagnosis for an adult presenting with bullae at the fingertips. The differential diagnosis for this presentation also includes herpetic whitlow, epidermolysis bullosa, bullous impetigo, and friction blisters.