Dermatologic Fungal Neglected Tropical Diseases-Part I. Epidemiology and Clinical Features.

In this part 1 of a 2-part continuing medical education series, the epidemiology, clinical features, and diagnostic methods for fungal skin neglected tropical diseases (NTDs), which include eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis, are reviewed. These infections, several of which are officially designated as NTDs by the World Health Organization (WHO), cause substantial morbidity and stigma worldwide and are receiving increased attention due to the potential for climate change-related geographic expansion. Domestic incidence may be increasing in the setting of global travel and immunosuppression. United States dermatologists may play a central role in early detection and initiation of appropriate treatment, leading to decreased morbidity and mortality.

Dermatologic Fungal Neglected Tropical Diseases-Part II. Management and Morbidity.

In this part 2 of a 2-part continuing medical education series, the management, outcomes, and morbidities for fungal skin neglected tropical diseases (NTDs), including eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis are reviewed. While fungal skin NTDs are associated with poverty in resource-limited settings, they are more often associated with immunosuppression and global migration in the United States. These infections have a high morbidity burden, including disfigurement, physical disability, coinfection, malignant transformation, mental health issues, and financial impact. For most fungal skin NTDs, management is difficult and associated with low cure rates. Dermatologists play a central role in initiating appropriate treatment early in disease course in order to improve patient outcomes.

A case of filgrastim-induced neutrophilic dermatosis of the dorsal hands in a patient with Felty Syndrome.

Neutrophilic dermatosis of the dorsal hands (NDDH) is a variant of Sweet syndrome that presents with erythematous bullae, papules/plaques, or pustules on the dorsal hands. It is most commonly associated with hematologic and solid organ malignancies, though cases of NDDH associated with inflammatory bowel disease, rheumatologic disorders, and medication exposure have also been described in the literature. Felty syndrome is a rare complication of long-standing rheumatoid arthritis characterized by neuropathy, splenomegaly, and neutropenia. Granulocyte colony stimulating factors (e.g., filgrastim) can be utilized to rescue the neutropenia observed in Felty syndrome, but this treatment may subsequently cause Sweet syndrome. Herein, we present a 64-year-old man with Felty syndrome and a complex medical history who presented with sudden onset, painful blisters located on the dorsal and palmar aspects of his bilateral hands. Given the patient's past medical history, a broad differential diagnosis, including disseminated fungal and viral infection was initially considered. A punch biopsy of the skin lesion disclosed neutrophilic dermatosis, which together with laboratory data satisfied the von den Driesch criteria for Sweet syndrome. As the lesions were localized exclusively on the patient's hands, the qualification of NDDH was also endorsed.

Future Fungal Fighters in Dermatology: Novel Antifungal Drug Pipeline.

Over the last decade, major advances in antifungal drug development have occurred. Novel drugs in the pipeline include ME1111, MAT2203, rezafungin, ibrexafungerp, olorofim, fosmanogepix, MGCD290, VT-1161, NP213, T-2307, aureobasidin A, and nikkomycin Z. While most of these “future fungal fighters” have been developed to address invasive fungal infections (IFI), there is potential for dermatologists to benefit as these drugs may be adapted for superficial infections. Here, we review the major developments in novel antifungals and examine the ways in which dermatologists may gain from these recent innovations. J Drugs Dermatol. 2022;21(5):496-501. doi:10.36849/JDD.6373.

Therapeutic Approaches and Special Considerations for Treating Molluscum Contagiosum.

Molluscum contagiosum (molluscum) is a common skin condition, especially in children, yet treatment approaches by US health care practitioners vary widely. A dearth of clinical data from large, well-controlled studies has resulted in significant gaps in knowledge, including treatment guidelines and algorithms. As of this writing, there are no FDA-approved treatments for molluscum. The objective of this review is to provide practitioners with expert, evidence-based information and guidance about treatment approaches for, and the special circumstances faced by, patients with molluscum. To this end, a group of five pediatric and adult dermatologists collectively identified treatments and special considerations they felt were most commonly used to treat molluscum. Hence, in the first part of the review, seven treatment approaches identified as the most important to review (e.g., curettage, cantharidin) are discussed in terms of their mechanisms of action, supporting clinical data, and rationale for use. Each treatment approach concludes with a “clinical pearls” section, which summarizes the group’s experiences with the treatment. In the second part, five special considerations (e.g., atopic dermatitis, skin of color) are discussed with supporting clinical data and are also followed by a “clinical pearls” summary. J Drugs Dermatol. 2021;20(11): 1185-1190. doi:10.36849/JDD.6383.

Intramuscular lipoma of the scapular region.

Intramuscular lipomas are rare, benign soft tissue neoplasms characterized by infiltrative growth into muscle tissue or between muscle fibers. These benign tumors can present similarly to malignant soft tissue neoplasms, such as liposarcomas. Unlike subcutaneous lipomas, intramuscular lipomas require diagnostic imaging to better distinguish the tumor and rule out alternative, malignant etiologies. It is imperative that dermatologists are able to identify this rare lipoma variant and have a thorough understanding of the diagnosis, imaging, and treatment options for this uncommon soft tissue tumor. Our case serves as a reminder for dermatologists to be cognizant of this rare tumor and aware of the importance of diagnostic testing in ruling out similarly-presenting, soft tissue malignancies.

Ingenol Mebutate: Expanded Utility

Ingenol mebutate (IM) is a novel drug that was developed for the treatment of actinic keratosis (AK). The drug works by a dual mechanism of action -- a rapid induction of cell death by necrosis along with a delayed neutrophil-mediated cellular cytotoxicity response.¹ Currently, IM is available as a 0.015% or 0.05% topical gel and has only been FDA-approved for the treatment of actinic keratosis. However, IM has also been extensively used off-label, and found to be efficacious in the treatment of multiple other skin disorders. In this review, we discuss the current literature that provides evidence for the successful use of ingenol mebutate as treatment for dermatologic disorders beyond actinic keratosis. J Drugs Dermatol. 2020;19(2)156-161. doi:10.36849/JDD.2020.4731

Probable African Tick Bite Fever in the United States.

African tick bite fever (ATBF) is a tick-borne rickettsial disease most often observed in North American and European tourists returning home from the southern portion of Africa. Ticks infected with Rickettsia africae transmit this parasitic bacterium to humans, who subsequently develop an influenza-like illness, one or more inoculation eschars, and in some cases, a cutaneous rash. Because ATBF often presents with non-specific symptoms that suggest other infectious diseases, establishing the diagnosis may be difficult. Confirmatory assays, including serology and nucleic acid amplification, may take weeks to return and cannot help with acute treatment decisions. We present a case of a previously healthy 60-year-old woman who developed an illness strongly suggestive of ATBF after a missionary trip to Zimbabwe and discuss the disease's diagnostic challenges. Our paper also reviews the epidemiology of this disease and the currently available diagnostic laboratory tests and recommended treatment options.

What are the ethical and legal considerations when your patient refuses the standard of care?

In medical practice, physicians are sometimes faced with patients who reject the gold-standard treatment for a condition. In this hypothetical clinical scenario, we present the case of a patient who refuses Mohs micrographic surgery for management of infiltrative basal cell carcinoma and instead requests off-label therapy with imiquimod. We discuss the treating dermatologist's options in response to this patient's request and the ethical considerations surrounding the case. We conclude that the physician has the right to refuse to provide treatment that deviates from standard clinical practice but that the physician should counsel the patient on all options, provide thorough informed consent, offer contact information for the patient to pursue a second opinion or a radiation oncology referral, and ensure safe transfer of care should the patient desire treatment with a different provider.

A Phase 2 Controlled Study of SB206, a Topical Nitric Oxide-Releasing Drug for Extragenital Wart Treatment.

BACKGROUND: Nitric oxide (NO), a free radical gas, is endogenously produced in human cells. In high concentration, NO neutralizes many disease-causing microbes. The topical investigational drug SB206 releases NO and has the potential to treat skin diseases caused by viruses. Genital warts (condyloma acuminata) are primarily caused by human papillomavirus (HPV) types 6 and 11. Available treatments have low tolerability and efficacy rates and are inconvenient for the patient. Genital warts can recur if HPV is incompletely eradicated during treatment. OBJECTIVE: Topical SB206 (berdazimer sodium plus carboxymethyl cellulose hydrogel) was assessed for tolerability, safety, and efficacy for up to12 weeks in patients with external genital and/or perianal warts (EGW/PAW) in a phase 2, double-blind, randomized, dose-escalation study. METHODS: Patients (N=108) were randomly assigned to SB206 or vehicle in a 3:1 ratio: SB206 4% once (QD) or twice daily (BID), 8% QD, 12% QD, or corresponding vehicle. Treatment duration was up to 84 days. The primary efficacy endpoint was complete clearance of baseline EGW/PAW at or before week 12. Pearson's Chi Square tests compared the efficacy of active vs vehicle treatments. Safety was assessed through adverse event and tolerability reports, physical examination findings, and clinical laboratory test results. RESULTS: In the Intent-to-Treat population, the percentage of patients with complete clearance of baseline EGW/PAW at or before week 12 was higher for SB206 groups than for vehicle groups, with the greatest difference between SB206 12% QD (33.3%; P=0.010) and vehicle QD (4.3%). CONCLUSION: Berdazimer sodium (SB206) plus hydrogel was efficacious and well tolerated in the treatment of EGW/PAW. J Drugs Dermatol. 2018;17(10):1100-1105.

Topical Antibacterial Agent for Treatment of Adult and Pediatric Patients With Impetigo: Pooled Analysis of Phase 3 Clinical Trials.

Ozenoxacin is a novel topical antibacterial agent with potent bactericidal activity against Gram-positive bacteria that has been developed as a 1% cream for treatment of impetigo. This article presents pooled results of pivotal clinical trials of ozenoxacin with the objective of evaluating the efficacy, safety, and tolerability of ozenoxacin 1% cream after twice-daily topical treatment for 5 days in patients with impetigo. A pooled analysis was performed of individual patient data from two multicenter, randomized, double-blind, vehicle-controlled phase 3 registration studies conducted in patients with impetigo. Both clinical trials followed a similar methodology. Patients were randomized 1:1 to ozenoxacin or vehicle. One trial included retapamulin as an internal control. Efficacy was measured using the Skin Infection Rating Scale and microbiological culture. Safety and tolerability were evaluated. Ozenoxacin demonstrated superior clinical success versus vehicle after 5 days of therapy, superior microbiological success versus vehicle after 2 days of therapy, and was safe and well-tolerated. Ozenoxacin showed superior clinical and microbiological response versus vehicle in children as young as 2 months of age, and adults, with impetigo. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT01397461 and NCT02090764; European Clinical Trials Database Number: 2011-003032-31 and 2014-000228-52. J Drugs Dermatol. 2018;17(10):1051-1057.

Recurrence of moderately dysplastic nevi with positive histologic margins.

BACKGROUND: The Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group recently published a consensus statement that incompletely excised moderately dysplastic nevi (MDN) without clinical residual pigmentation can be observed and not re-excised. However, data regarding recurrence of MDN with positive histologic margins are quite scant. OBJECTIVE: We sought to extend the reported findings with a study to determine the recurrence rate of MDN with positive histologic margins. METHODS: We performed a retrospective study on MDN with positive histologic margins that were not re-excised and for which at least 1 year of clinical follow-up was available. RESULTS: We found a total of 147 such nevi from January 1, 2007, to December 31, 2013. Six MDN (5 compound and 1 junctional) or 4% recurred with an average recurrence time of 1.7 years. All of these MDN were evaluated by shave biopsies. LIMITATIONS: Subjectivity in grading of atypia is a limitation of this study. CONCLUSION: These data from a large study focusing exclusively on recurrence of MDN with positive histologic margins support the conclusion of the Pigmented Lesion Subcommittee that incompletely excised MDN do not require re-excision.

Cutaneous leishmaniasis mimicking squamous cell carcinoma.

A 41-year-old man from Cuero, Texas with a nonhealinglesion on his left cheek was referred to ourclinic for removal of a squamous cell carcinoma. Thepatient first noticed a "pimple" on his left cheek 3-4months prior to presentation. When the lesion beganto grow he presented to his primary care physician anda biopsy was taken, showing "atypical squamous cellproliferation." Mohs surgery was performed and thenodule was removed with no evidence of malignancyseen on histopathology. Upon review of the surgicalbiopsies by consulting pathologists, the diagnosis ofleishmaniasis was established and later confirmed bythe Center for Disease Control and Prevention (CDC)as Leishmania mexicana. The patient was referred toinfectious disease specialists for further management.

Concepts in Onychomycosis Treatment and Recurrence Prevention: An Update.

In considering therapy for onychomycosis, the most important factor to take into account is patient selection rather than treatment selection. Patients should be screened and evaluated for the extent of nail involvement, the amount of subungual debris, the degree of dystrophy, their ability and willingness to follow the regimen, and whether comorbidities are present that may affect the efficacy and/or safety of one or more therapies. Onychomycosis is a chronic disease with a high recurrence rate. Commonsense measures to reduce the risk for reinfection include patient education and a clinician-patient team approach to long-term management.

Tinea and Onychomycosis.

Onychomycosis and tinea pedis are common fungal infections affecting the nails and feet, respectively. Two newly approved topical agents for onychomycosis are efinaconazole and tavaborole, both of which have demonstrated respectable cure rates in clinical studies. For tinea pedis, naftifine 2% and luliconazole 1% are new agents, both administered for relatively short courses, that may foster greater adherence Semin Cutan Med Surg 35(supp6):S110-S113.

Antifungal Drugs for Onychomycosis: Efficacy, Safety, and Mechanisms of Action.

In 1996, oral terbinafine joined itraconazole and fluconazole on the short list of systemic medications that could be used to treat onychomycosis (although fluconazole was not approved for this indication by the US Food and Drug Administration [FDA], it was commonly used for this purpose). In 1999, ciclopirox was the first topical treatment to be FDA approved. The addition of the topical antifungal agents efinaconazole and tavaborole in 2014 expanded the roster of medications available to more effectively manage onychomycosis in a wide range of patients, including those for whom comorbid conditions, concomitant medications, or patient preference limited the use of systemic antifungals.

Assessment of Dermatophytosis Treatment Studies: Interpreting the Data.

Antifungal therapy has recently enjoyed a resurgence of interest due to the introduction of a number of new formulations of topical drugs and novel molecules. This has led to a plethora of new publications on management of cutaneous fungal disease. This paper summarizes the various clinical trial factors which may affect the published data regarding how well antifungal drugs work. Understanding these parameters allows the healthcare provider to choose more rationally between available agents based upon an assessment of the evidence.

Onychomycosis: epidemiology, diagnosis, and treatment in a changing landscape.

Onychomycosis is an often overlooked and/or undertreated disease. This may be in part due to an under appreciation among both physicians and patients of its impact on quality of life and the potential for significant complications, from tinea corporis and cruris, to bacterial superinfection. Some health care providers are unaware of the effective low-risk treatments currently available. Changing demographic characteristics such as the relative aging of the population; the increasing prevalence of diabetes and peripheral vascular disease, and widespread iatrogenic immunosuppression; and changes in lifestyle practices such as earlier and greater participation in sports, are likely to lead to an increased prevalence of onychomycosis in both adults and children. Two topical onychomycosis treatments, efinaconazole 10% solution, and tavaborole 5% solution were recently approved by the FDA. This article reviews the state of knowledge and describes, briefly, these new treatment options.