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.

Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

The Curious Case of a Painful Leg Ulcer.

Sickle cell disease is a condition that can involve numerous organ systems secondary to vascular occlusion. Herein, we present a case of a 21-year-old male with sickle cell disease requiring long-term hydroxyurea therapy. Upon migrating to the United States from Yemen, the patient developed a rapidly progressive, exquisitely painful ulcer on his right lower extremity. Given his country of origin, a broad differential, including select infectious diseases, was essential. Moreover, establishing the unequivocally correct diagnosis was crucial to determine proper and safe therapy. Ultimately, a lesional biopsy demonstrated numerous sickled red blood cells occluding blood vessels, leading to the diagnosis of sickle cell disease-related leg ulceration.

Chromoblastomycosis Presenting as a Solitary Lesion in a Non-endemic Region.

Chromoblastomycosis is a neglected tropical disease typically found in endemic tropical and subtropical regions. Herein, we discuss a rare case of a 55-year-old man in Texas who presented with an exophytic papule on the forearm, diagnosed to have chromoblastomycosis by shave biopsy and subsequent histopathological analysis. Treatment options for chromoblastomycosis include long-term oral antifungal therapy with itraconazole, physical modalities such as heat therapy in conjunction with oral antifungals, and surgical interventions such as cryosurgery or surgical excision.

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.

"The Raven Himself Is Hoarse:" Candida dubliniensis fungemia manifesting as an eschar.

A 65-year-old man with diabetes, end-stage renal disease on hemodialysis, coronary artery disease, and a prosthetic aortic valve. He presented to the emergency department with hypothermia (96.6°F), several weeks of anorexia and chills, and bilateral lower extremity tissue necrosis with erythema and edema (Figure 1A). He had a peripherally inserted central catheter (PICC) line 8 weeks prior placed at another hospital for treatment of cellulitis. Laboratory results revealed anemia, azotemia, and leukocytosis (19,200 WBCs/mm3), and he was admitted for sepsis of unknown etiology. (SKINmed. 2022;20:213-214).

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.

Public interest in skin lightening across the United States, January 2015-December 2020.

Skin lightening is a popular practice across the world, especially in India, the Philippines and other Asian countries, and some Caribbean nations. It is a dangerous trend, as some of the products used to achieve a lighter skin tone have been shown to often contain unsafe chemicals. In this article, we examine trends in consumer interest in skin lightening using a Google Trends query of 4 search terms: "skin lightening," "skin brightening," "skin whitening," and "skin bleaching," across the United States from 2015 to 2020, and demonstrated that it is most popular in states with diverse populations, including a high percentage of black and Asian Americans.

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.

Sexually Transmitted Diseases in the COVID-19 Era.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an infectious disease of recent origin with high transmissibility and mortality. The resulting COVID-19 pandemic has impacted the United States the most, in terms of the number of confirmed cases and fatalities. How other aspects of public health will be impacted by this disease has yet to be fully realized. Sexually transmitted diseases (STDs), already a major public health crisis, will likely be significantly affected by this pandemic. We address some of the potential implications for STDs in the setting of widespread COVID-19, discussing the sexual transmission of COVID-19 itself, STD co-infection with COVID-19, and changes in STD prevalence secondary to COVID-19. (SKINmed. 2020;18:210-212).

iPLEDGE Must Abstain from Abstinence.

Isotretinoin has unmatched efficacy in the treatment of acne. However, because isotretinoin is a teratogen that can cause profound birth defects, the iPLEDGE program regulates the drug's distribution in the United States. To minimize fetal exposure to isotretinoin, the program requires that female patients capable of becoming pregnant use two forms of contraception or commit to abstinence while using this therapy. This manuscript argues that iPLEDGE should be revised to remove abstinence as an acceptable contraceptive option in the face of evidence that disputes its efficacy. All patients, regardless of reported sexual activity, should be required to use data-proven contraception. Potential benefits of the proposed change (iPLEDGE-R) include reducing the number of isotretinoin pregnancies, increasing patient privacy protection, and standardizing patient care. Further investigation needs to guide additional strategies to achieve the program's public health goal; however, the ethical and pragmatic advantages of iPLEDGE-R merit consideration.

Unmasking Masks.

Masks are coverings of the face that serve a variety of purposes. Throughout history, they have been used for religious ceremonies, theatric entertainment, protection of identity, and as a tool to limit the spread of infectious diseases. The development of masks in the medical setting has evolved along with our understanding of the mode of disease transmission, material science, and population health dynamics. The simple barrier face mask, surgical mask, and filtering facepiece respirator are each appropriate in different settings. Establishing evidence-based guidance behind the use of masks is essential, particularly in public health crises.

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.

Safety and efficacy profile of ozenoxacin 1% cream in pediatric patients with impetigo.

BACKGROUND: Ozenoxacin is a topical antibiotic approved in the United States for treatment of impetigo in adults and children age ≥2 months. This analysis evaluated the efficacy and safety of ozenoxacin in specific pediatric age groups. METHODS: Data for children aged 2 months to <18 years recruited from eight countries who had participated in phase 1 and 3 trials of ozenoxacin were extracted and analyzed by age range. RESULTS: Across studies, 644 pediatric patients with impetigo received ozenoxacin 1% cream (n = 287) or vehicle (n = 247). One study included retapamulin 1% ointment as the internal validity control (n = 110). The clinical success rate at the end of treatment and bacterial eradication rates after 3 to 4 days of treatment and at the end of treatment were significantly higher with ozenoxacin than vehicle (all p < .0001). The clinical and microbiologic success rates were higher with ozenoxacin than vehicle in the age groups of 0.5 to <2 years, 2 to <6 years, 6 to <12 years, and 12 to <18 years and were comparable to vehicle in the 2 to <6 months age group, although patient numbers were low (≤5 per treatment arm). No safety concerns with ozenoxacin were identified. Of the 362 plasma samples derived from 38 patients, four slightly exceeded the lower limit of quantification, indicating negligible systemic absorption. CONCLUSION: The results of this analysis suggest that ozenoxacin 1% cream is an effective and safe treatment for impetigo in pediatric patients aged 2 months to <18 years.

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

Superficial Basal Cell Carcinoma of the Face Successfully Treated with Ingenol Mebutate 0.05% Gel: Case Report and a Review of the Literature.

A 64 year-old Caucasian male patient with a long history of ultraviolet light exposure and multiple actinic keratoses presented with a large, erythematous, and scaly plaque on his forehead. Biopsies revealed superficial basal cell carcinoma (sBCC). Because the patient wanted the shortest possible topical regimen, his sBCC was treated with two overnight ingenol mebutate (IM) 0.05% gel applications. He tolerated the local skin reaction (LSR) well, and at approximately six weeks post-treatment, biopsies showed no evidence of sBCC. The patient was happy with the cosmetic outcome and has remained free of clinical recurrence for 18 months. Although IM gel is only FDA approved for the treatment of actinic keratosis, it has also been used off-label to treat other epithelial lesions, including basal cell carcinoma (BCC), anogenital warts, and Bowen's disease. One clinical trial, multiple case series and case reports, and now this report, have demonstrated IM's utility in treating BCC. IM treatment is therefore a promising alternative to surgery for select BCC, with major advantages, including a short treatment duration and generally favorable cosmetic outcome.