Journal Review Series: April-June 2019

Next Steps in Derm author, Dr. Anna Chacon, searched the journals so that you don’t have to! She reports on important take-aways from different dermatology journals for the months of April, May, and June of 2019.

It is key to keep in mind that “important” is subjective and what is contained in this review is one person’s view of what should be remembered from these months of the literature.

April 2019

Onychomycosis: Clinical overview and diagnosis

 

Epidemiology

• • The worldwide prevalence of onychomycosis is 5.5%
  • Onychomycosis is less common in children and more common in older individuals

Risk factors

• • Trauma, older age, diabetes, and immunosuppression predispose to onychomycosis
  • Tinea pedis, psoriasis, and family history of onychomycosis are other risk factors

Pathogenic organisms

• • Dermatophytes, particularly Trichophyton rubrum, are responsible for most fungal nail infections
  • About 30% to 40% of onychomycosis cases are caused by nondermatophyte molds and yeasts
  • Biofilms have recently been recognized to play an important role in the pathogenesis of onychomycosis

Clinical presentation

• • Onychomycosis has physical and social consequences
  • The most common presentation of onychomycosis is yellowing, onycholysis, and subungual hyperkeratosis
  • The most common dermoscopic pattern of onychomycosis is a jagged proximal border with spikes in the onycholytic area

Clinical classification

• • Distal lateral subungual onychomycosis is the most common clinical pattern
  • Proximal subungual onychomycosis is associated with immunosuppression

Diagnostic testing

• • Confirmatory testing should be performed before initiating treatment for onychomycosis
  • Direct microscopy, fungal culture, and histopathology may be used for confirmation
  • Polymerase chain reaction may be used to rapidly identify the infecting organism

Future directions

• • Confocal microscopy and optical coherence tomography are emerging techniques for the confirmation of onychomycosis
  • Limitations include specialized training and cost

Onychomycosis: Treatment and prevention of recurrence

Prognosis and response to treatment

• • Patient characteristics, nail findings, and infecting organisms contribute to response to antifungal therapy
  • The Onychomycosis Severity Index can be used to predict response to antifungal therapy

Systemic treatments approved by the FDA

• • Oral terbinafine and itraconazole are approved by the FDA for the treatment of onychomycosis
  • Because of higher cure rates with terbinafine and fewer drug interactions, terbinafine is usually preferred over itraconazole

Off-label systemic treatments

• • Fluconazole is an alternative off-label systemic treatment for onychomycosis with broad-spectrum antifungal coverage
  • Terbinafine may be dosed in pulses with similar cure rates to continuous dosing
  • Treatment of onychomycosis in children is off-label, with terbinafine and itraconazole considered first-line therapies

Topical treatments approved by the FDA

• • Ciclopirox 8% nail lacquer is approved by the FDA for the treatment of fingernail and toenail onychomycosis with some data on off-label use in children
  • Efinaconazole 10% solution and tavaborole 5% solution are newer therapies approved by the FDA for toenail onychomycosis with favorable efficacy

Laser therapy

• • Lasers are approved by the FDA for “temporary increase of clear nail in patients with onychomycosis,” not cure
  • Since cure rates for laser treatment are lower than those for orals and topicals, lasers are not recommended as first-line therapy for onychomycosis

Treatments in development

• • Photodynamic and plasma therapies have been explored for the treatment of onychomycosis, but larger randomized trials are needed to determine their efficacy and practicality in the clinical setting

Angioinvasive fungal infections impacting the skin: Background, epidemiology, and clinical presentation

Candidiasis

• Invasive candidiasis is the leading cause of mycosis-associated mortality in the United States
• There is a growing number of medically relevant Candida species, including the recently recognized Candida auris
• Disseminated candidiasis is more severe in immunocompromised hosts and neonates

Aspergillosis

• Invasive aspergillosis infections have increased since 1980
• Infection often occurs at sites of skin breakdown, trauma, adhesive dressings, venipuncture or catheter insertion sites, and burn scars
• Presentation in disseminated disease can be atypical in immunocompromised hosts

Mucormycosis

• Mucormycetes, previously referred to as zygomycetes, includes several genera: Rhizopus, Mucor, Rhizomucor, Lichtheimia, Saksenaea, Cunninghamella, and Apophysomyces
• Diabetes is a major risk factor for disseminated mucormycosis
• Mucor spp sequester iron from their hosts, indicating iron overload syndromes as an additional risk factor in disseminated disease

Other hyaline molds

• Cutaneous involvement can be seen in approximately 75% of cases of disseminated Fusarium infection
• Hyalohyphomycoses often present with eumycetoma

Phaeohyphomycosis

• Phaeohyphomycoses are rare but can cause infection in both immunocompetent and immunocompromised hosts
• Melanin production in these organisms plays a key role in fungal infectivity and virulence

Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): A phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate to severe atopic dermatitis (AD)

• The substantial patient burden associated with moderate to severe atopic dermatitis demonstrates need for effective therapies.
• Dupilumab resulted in significant and clinically relevant improvements in patient-reported outcomes assessing symptoms and health-related quality of life.
• Dupilumab effects on patient-reported outcomes complemented clinical measures, demonstrating efficacy for atopic dermatitis across multiple domains important to patients.

This study demonstrated significant improvement of atopic dermatitis with dupilumab and established improved outcomes at dosing of 300 mg.

 

Standardized laboratory monitoring with use of isotretinoin in acne

• • The optimal timing of laboratory tests for patients undergoing isotretinoin treatment for acne is uncertain.
  • In this series, although abnormalities in serum lipid levels in patients receiving isotretinoin were not infrequent, they were mild to moderate and were generally noted around the second month of treatment.
  • For healthy patients who are taking isotretinoin, we recommend that a lipid panel and liver function tests be performed at baseline and at month 2 when peak dosing is achieved. Further testing should be considered if a significantly abnormal value is noted.

This very important article suggests that we are over monitoring for our patients who are taking isotretinoin. Liver function tests and lipid panels may be necessary only after month 2, and complete blood counts are not necessarily going to change patient outcomes. This is important to avoid unnecessary blood draws and expenditure of health care dollars.

Angioinvasive fungal infections impacting the skin: Background, epidemiology, and clinical presentation

Diagnosis and workup

• • Obtaining a sterile punch biopsy specimen and a fungal culture are standard components of the diagnostic workup
  • It is important to notify the microbiology laboratory if mucormycosis is suspected because tissue samples should be handled gently (ie, no grinding or stomaching); this decreases the likelihood of a false negative
  • Frozen sectioning or touch preparations of a punch biopsy specimen can be an effective method to quickly ascertain the presence of fungal organisms in tissue

Histopathology

• • Histopathology can help identify fungi and their morphologic features regarding septated hyphae and pigmentation, but it is not possible to completely accurately speciate a fungal organism subtype via histology alone
  • The presence of septated hyphae largely rules out Mucorales spp, which present as non-septated and wide, ribbon-like organisms
  • Septated and non-pigmented hyphae can represent several hyalohyphomycotic species, including Fusarium spp, Aspergillus spp, and Pseudallescheria spp
  • Candida spp will demonstrate a range of morphologies, most commonly budding yeast and pseudohyphae, although Candida glabrata does not form true hyphae or pseudohyphae and may mimic histoplasmosis

Tissue culture

• • Tissue culture provides pathogen speciation and treatment susceptibilities
  • Aspergillus spp should be considered a true pathogen if isolated in an immunocompromised patient
  • Growth rates vary widely by species, and adequate time for growth is important

Blood culture

• • For disseminated candidiasis, positive blood culture is the gold standard
  • Infection by Fusarium spp has a high frequency of positive blood cultures, as Fusarium spp sporulate in vivo

Imaging

• • Imaging can be helpful to identify other organ involvement in angioinvasive fungal infections
  • Computed tomography imaging of the sinuses and chest is necessary for suspected rhinocerebral and disseminated mucormycosis, respectively
  • In disseminated candidiasis, with elevated liver enzymes or hepatosplenomegaly, computed tomography and magnetic resonance imaging are 90% sensitive in determining hepatosplenic involvement
  • The brain and respiratory tract are preferred sites for disseminated aspergillosis
  • Computed tomography imaging of the brain and chest are indicated in high-risk patients with neurologic or respiratory symptoms

Additional tests

• • When negative, galactomannan antigen and 1,3-beta-D-glucan assays are useful for ruling out disseminated mucormycosis
  • The galactomannan antigen assay is positive in Aspergillus spp, but also cross-reacts with Fusarium spp, Talaromyces marneffei, and Histoplasma capsulatum
  • The 1,3-beta-D-glucan assay can detect Aspergillus spp, Candida spp, Pneumocystis jiroveci, Pseudomonas aeruginosa, and occasionally Cryptococcus neoformans
  • The T2Candida assay is a panel that can detect very low levels of candidemia caused by C albicans, Candida tropicalis, Candida parapsilosis, C glabrata, and C krusei

Treatment

• • Empiric therapy, such as liposomal or lipid-based amphotericin B and posaconazole, should be started promptly in severely ill patients with suspected angioinvasive fungal infection
  • Intravenous echinocandin therapy is first-line for disseminated candidiasis and fluconazole is no longer recommended because of resistance
  • For severe invasive aspergillosis, voriconazole and an echinocandin agent should be used in immunocompromised patients
  • Empiric treatment with intravenous liposomal amphotericin B and aggressive surgical debridement is recommended in patients with suspected mucormycosis

Complications

• • Prompt initiation of treatment is essential to prevent severe morbidity and mortality

An Open Label Study of an Occlusive Heat Patch in the Treatment of Warts

Local hyperthermia delivered by epicutaneous heat patches was well-tolerated, safe, and achieved complete clearance in both treated as well untreated warts in 46.7% of participants at week 24 after 12 weeks of daily use.

Non-Surgical Fat Reduction and Topical Modulation of Adipose Tissue Physiology

Non-surgical fat reduction procedures results in accumulation of breakdown products, lipid droplets, that are slowly absorbed over a period of months. Lipid droplets are absorbed through a process of autophagy (lipophagy) involving a repackaging of these droplets to smaller sizes so that macrophages can then cope with digestion of these very large particles. A fat compartment is described within the dermis surrounding the tail of the hair follicle, which is attracting much attention due to its unique phenotype, function, and connection to the deeper subcutaneous fat compartment. This provides an entry route for direct signaling to the subcutaneous fat. Related to these novel concepts, peptides can be designed in liposomal delivery systems to target lipid droplet breakdown via the hair follicle entry route.

Treatment of Psoriasis With Biologics and Apremilast in Patients With a History of Malignancy: A Retrospective Chart Review

The data reviewed here show successful treatment on biologics despite concurrent malignancy, though confirmatory research is needed.

Adapting to the Effects of Climate Change in the Practice of Dermatology—A Call to Action

In October 2018, the United Nations Intergovernmental Panel on Climate Change (IPCC) released its landmark special report. Written by 91 authors from over 40 countries, it presented a stark characterization of the consequences of climate change. In addition to elucidating the irreversible effects of the 1.0°C rise in average global temperature that has occurred since the industrial revolution began, the IPCC warned, in a global call to action, that limiting further warming to only 1.5°C will require rapid, expansive, and unprecedented changes to human behavior by 2030.1 Shortly thereafter, the Fourth National Climate Assessment from the US government echoed these concerns: mitigation and adaptation efforts … do not yet approach the scale considered necessary to avoid substantial damages to the economy, environment and human health over the coming decades. Unfortunately, the ongoing politicization of climate change makes it challenging to take necessary actions. Physicians can provide a trusted voice to educate the public about the health hazards of climate change. Dermatologists, too, should become versed in the ways it threatens patients, practices, and well-being.

Association of Systemic Antibiotic Treatment of Acne With Skin Microbiota Characteristics

Systemic antibiotic treatment of acne may be associated with transient and persistent changes in the skin microbiota that may underlie skin comorbidities related to microbial dysbiosis. In this study of 4 women with acne, there was a significant decrease in the relative abundance of Cutibacterium acnes (formerly Propionibacterium acnes) concurrent with a significant increase in the relative abundance of Pseudomonas species across participants following 4 weeks of treatment with oral minocycline. After 8 weeks of antibiotic treatment withdrawal, C acnes levels recovered, while Streptococcus species significantly increased and Lactobacillus species significantly decreased from baseline.

Understanding the association between systemic antibiotic use and skin microbiota may help clinicians decrease the likelihood of skin comorbidities related to microbial dysbiosis. In this study, systemic antibiotic treatment of acne was associated with changes in the composition and diversity of skin microbiota, with variable rates of recovery across individual patients and parallel changes in specific bacterial populations.

Use of Antibiotics for Dermatologic Procedures From 2008 to 2016

Oral antibiotic prescribing by dermatologists associated with benign excisions, malignant excisions, and Mohs surgery is increasing over the past decade and there is substantial geographic variation. These findings indicate that there may be opportunities to optimize antibiotic use associated with dermatologic procedures.

Development and Validation of a Risk Prediction Model for In-Hospital Mortality Among Patients With Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis—ABCD-10

In this cohort of patients with SJS/TEN, ABCD-10 (age, bicarbonate, cancer, dialysis, 10% BSA) accurately predicted in-hospital mortality, with discrimination that was not significantly different from SCORTEN. Additional research is needed to validate ABCD-10 in other populations. Future use of a new mortality prediction model may provide improved prognostic information for contemporary patients, including those enrolled in observational studies and therapeutic trials.

May 2019

Hair disorders in patients with cancer

Epidemiology

• • Hair changes attributed to anticancer therapies are expected to occur in ≥65% of patients receiving cytotoxic therapies, 15% with targeted therapies, <2% on immunotherapies, and up to 100% in areas treated with radiotherapy

Clinical features

• • The spectrum of hair disorders in cancer patients encompasses all hair changes, including alopecia, pigmentary changes, textural changes, and cycle alterations

Etiology and pathogenic mechanisms

• • The pathogenic mechanisms of anticancer therapy–induced alopecia and other hair disorders varies depending on causal therapy
  • The hair matrix keratinocytes of anagen hair follicles have a high mitotic activity, which makes them especially vulnerable to anticancer therapies
  • Paradoxically, some anticancer therapies can promote hair growth and textural and hair color changes

Hair disorder severity grading

• • Adverse events in oncology clinical trials are graded using the Common Terminology Criteria for Adverse Events

Quality of life in patients with cancer with hair disorders

• • Chemotherapy-induced scalp, eyelash, and eyebrow alopecia lead to a negative psychosocial impact
  • The impact of other hair disorders in oncology has not been reported but is likely significant

Management

• • Most preventive or reactive strategies are based on uncontrolled studies; however, the US Food and Drug Administration has cleared 2 dynamic scalp cooling devices for the prevention of CIA in patients treated with cytotoxic chemotherapies for solid tumors

Hair disorders in cancer survivors

Alopecia in cancer survivors: overview and clinical features

• • There are an estimated 15.5 million cancer survivors in the United States, equivalent to 4.8% of the population. The majority have undergone a surgical procedure as part of their diagnosis or treatment, approximately 50% have been treated with radiotherapy, and >60% have received systemic anticancer therapies, all of which may result in persistent or permanent hair disorders
  • Thirty percent (30%) of breast cancer survivors treated with taxanes (paclitaxel or docetaxel) will develop persistent alopecia
  • Endocrine therapies are associated with pattern alopecia similar to androgenetic type in 15% to 25% of survivors
  • Head and neck radiotherapy leads to persistent alopecia in 60% of survivors
  • In survivors of childhood cancer, alopecia has been associated with anxiety and depression, and adult survivors with persistent alopecia report a negative impact on their emotions

Histopathology and pathobiology

• • Destruction of epithelial hair follicle stem cells by anticancer therapies prevents hair follicle cycling

Quality of life in cancer survivors with hair disorders

• • Persistent or permanent alopecia after cancer therapies has been associated with depression, anxiety, and increased somatization

Management

• • Management of hair disorders in cancer survivors is supported by anecdotal reports and case series that fail to meet strict evidence-based medicine standards

Acquired cold urticaria: Clinical features, particular phenotypes, and disease course in a tertiary care center cohort

• • Acquired cold urticaria is characterized by the development of wheals, angioedema, or both after cold exposure.
  • Age at diagnosis, disease severity, and response to the ice cube challenge test predicted both prognosis and response to therapy.
  • Proper characterization of the type of acquired cold urticaria enables appropriate counseling and choice of therapy.

This article identifies atypical acquired cold urticaria (ACU) as having a negative response to cold stimulation. When symptoms begin in childhood, there is a higher rate of atypical ACU and also a lower rate of complete symptom relief. In total, 19% of ACU patients can present with life-threatening reactions.

Acquired disorders with depigmentation: A systematic approach to vitiliginoid conditions

Chemical leukoderma

• • All cases of chemical leukoderma are preceded by a history of repeated chemical insult
  • Identifying and avoiding the offending agent frequently results in gradual repigmentation

Melanoma-associated leukoderma

• • Melanoma-associated leukoderma is not uncommon in patients with melanoma, particularly those treated with immune checkpoint blockade
  • Skin depigmentation resembling vitiligo in patients >50 years of age warrants a thorough skin examination, including the mucosal membranes, in addition to a focused ocular examination
  • The development of melanoma-associated leukoderma during immunotherapy is a marker of favorable prognosis

Vogt-Koyanagi-Harada disease and Alezzandrini syndrome

• • Vogt-Koyanagi-Harada disease should be considered in adults with progressive depigmentation that coincides with visual disturbances
  • HLA-DRB1*04 carriers are the primary group at risk for developing Vogt-Koyanagi-Harada disease
  • If a delay in ophthalmologic evaluation is anticipated and the patient has acute visual symptoms, high-dose systemic corticosteroids should be initiated to prevent further vision impairment

Scleroderma leukoderma

• • Depigmentation associated with perifollicular pigment retention is characteristic of scleroderma leukoderma and resembles repigmented vitiligo
  • Early juvenile localized scleroderma can present with cutaneous depigmentation that clinically and histologically resembles vitiligo
  • The management of scleroderma is complex and requires a multidisciplinary approach

Tropical diseases

• • Chronic onchocerciasis and tertiary pinta disease should be considered in migrants that have spent time in endemic regions
  • Subcutaneous nodules, hypo- or depigmented skin changes, persistent eosinophilia, and a travel history to an endemic region is pathognomonic of chronic onchocerciasis
  • Before treatment, patients with chronic onchocerciasis should be screened for Loa loa coinfection to prevent life-threatening encephalitis

Postinflammatory depigmentation

• • The primary morphology of the underlying inflammatory disease often provides a straightforward diagnosis
  • Localized skin depigmentation can occur after corticosteroid injections or skin trauma that occurs after severe scratching, cryotherapy, burns, or laser
  • Identifying and controlling or preventing the underlying etiology is the first step in managing postinflammatory depigmentation

Spontaneous neoplastic regression

• • In children, halo nevi follow a benign course, and reassurance is appropriate when features of melanoma are absent
  • A depigmented macule or patch can result from a completely regressed pigmented lesion
  • Metastatic melanoma has no detectable primary site in 4% to 10% of cases; however, a depigmented lesion located on skin that drains to an enlarged lymph node is sometimes identifiable

Other considerations

• • Depigmentation of the foreskin with dyspareunia is highly suggestive of lichen sclerosus
  • Localized depigmentation in the genital region can be the earliest sign of extramammary Paget disease or its recurrence
  • Obtaining a biopsy specimen may be required to establish a diagnosis of depigmented extramammary Paget disease or lichen sclerosus and to rule out squamous cell carcinoma

Acquired disorders with hypopigmentation: A clinical approach to diagnosis and treatment

Discrete hypopigmented macules

• • The prevalence of idiopathic guttate hypomelanosis increases with age and signs of photodamage commonly accompany the macules
  • A single session of cryotherapy is a quick and cost-effective treatment option for idiopathic guttate hypomelanosis
  • Chronic arsenic exposure should be considered when hypopigmented macules arise on a background of diffuse hyperpigmentation

Progressive macular hypomelanosis

• • Progressive macular hypomelanosis is a common cause of hypopigmentation in adolescent females
  • Red fluorescence, localized to the follicles under a Wood’s lamp, is pathognomonic for progressive macular hypomelanosis
  • Phototherapy is effective in inducing repigmentation; however, recurrence after treatment is common

Infectious etiologies of hypopigmentation

• • Indeterminate leprosy classically presents with a smooth, well-defined hypopigmented macule or patch on the extremities or face, without sensory changes
  • Macular post–kala-azar dermal leishmaniasis should be considered in patients who have traveled to East Africa or the Indian subcontinent

Neoplastic etiologies of hypopigmentation

• • The diagnosis of hypopigmented mycosis fungoides frequently requires obtaining multiple biopsy specimens
  • Hypopigmented mycosis fungoides follows a waxing and waning course, often requiring long-term treatment
  • Hypopigmented parapsoriasis en plaque is managed similarly to hypopigmented mycosis fungoides and frequently resolves within 2 years

Other considerations

• • Tyrosine kinase inhibitors may cause hypopigmented skin changes; repigmentation often occurs once the agent is discontinued
  • Corticosteroid injections can cause localized hypopigmentation that may expand along a lymphatic or venous distribution

Cortexolone 17α-propionate (Clascoterone) Is a Novel Androgen Receptor Antagonist that Inhibits Production of Lipids and Inflammatory Cytokines from Sebocytes In Vitro

Cortexolone 17α-propionate (clascoterone) is a novel topical androgen antagonist that is being analyzed for its ability to treat acne. Androgens induce the proliferation and differentiation of sebocytes, (cells that comprise the sebaceous gland), help regulate the synthesis of the lipids that are incorporated into sebum and stimulate the production of cytokines that are found in inflammatory acne lesions. Clascoterone was found to bind the androgen receptor (AR) with high affinity in vitro, inhibit AR-regulated transcription in a reporter cell line, and antagonize androgen-regulated lipid and inflammatory cytokine production in a dose-dependent manner in human primary sebocytes. In particular, when compared to another AR antagonist, spironolactone, clascoterone was significantly better at inhibiting inflammatory cytokine synthesis from sebocytes. Therefore, clascoterone may be an excellent candidate to be the first topical antiandrogen to treat acne.

Optimizing Patient Outcomes by Customizing Treatment With Microfocused Ultrasound With Visualization: Gold Standard Consensus Guidelines from an Expert Panel

Supported by a large body of clinical evidence, a well-characterized mechanism of action, and high patient satisfaction, micro focused ultrasound with visualization is considered by the expert panel of physicians to be a key foundation of aesthetic treatment and the gold standard for nonsurgical lifting and skin tightening.

Adalimumab versus Rifampicin Plus Clindamycin for the Treatment of Moderate to Severe Hidradenitis Suppurativa: A Retrospective Study
In the present single-center retrospective study, we investigated our data to evaluate the efficacy of the classic antibiotic combination (rifampicin and clindamycin) compared to adalimumab treatment in patients affected by moderate-to-severe hidradenitis suppurativa. The mean modified Sartorius Score before starting treatment was 74.93 while the value at week 10 was 39.86 (P less than 0.0001). The mean Hidradisk value before starting treatment was 77.73 while the value at week 10 decreased to 51.86 (P less than 0.0001). Eighteen patients (18/30) achieved the HiSCR.

Silicone-Based Scar Cream for Post Upper Eyelid Blepharoplasty-associated Cicatricial and Hypertrophic Scarring
The use of a topical silicone-based scar cream has been shown to be safe and effective in decreasing the incidence of intralesional injections of triamcinolone and 5-FU for postoperative cicatricial and hypertrophic changes in upper eyelid blepharoplasty incisions.

Non-Invasive Buccal Swab Gene Testing for Skin Cancer Risk
This data supports that 4 of the 7 SNP’s (single nucleotide polymorphisms) studied had similar associations and could potentially be predictive tool of NMSC risk in this patient population. The remaining three SNP’s did not have a definitive association with malignancy. Larger studies are needed to further elucidate the specific roles of these SNPs collectively and ultimately to develop a genetic profile for those patients at increased risk of developing skin cancer.

Effect of a Tranexamic Acid, Kojic Acid, and Niacinamide Containing Serum on Facial Dyschromia: A Clinical Evaluation

The findings suggest that the test product is an effective and well-tolerated treatment option for addressing hyperpigmentary conditions, including melasma. Additional in vitro data suggest that TXA may act by mediating the inhibition of PGE2-stimulated human epidermal melanocytes.

Hair Reduction for Transgender PersonsWhat Dermatologists Should Know and How They Can Help

Transgender serves as an umbrella term for individuals whose gender identity or gender expression differs from their sex assigned at birth. The transgender community represents 0.6% of US adults and includes transmen, transwomen, and other gender minorities (individuals who identify outside of the traditional gender paradigm). Hair reduction is critical for trans people with unwanted facial and body hair, and those who undergo gender-affirming surgery (surgical procedures to align an individual’s outward appearance, or gender expression, with their gender identity). Dermatologists will likely play an increasingly important role in providing hair-reduction services; therefore, they should be familiar with clinical and policy aspects of hair reduction for gender minorities. Dermatologists can take steps to improve access to hair-reduction services for trans people, consider techniques and indications and regulatory and insurance issues.

Second-Hit, Postzygotic PMVK and MVD Mutations in Linear Porokeratosis

Linear porokeratosis is associated with the presence of second-hit postzygotic mutations in the genes that encode enzymes within the mevalonate biosynthesis pathway. The mevalonate pathway may be a potential target for therapeutic intervention in porokeratosis.

Early Melanoma Nodal Positivity and Biopsy Rates Before and After Implementation of the 7th Edition of the AJCC Cancer Staging Manual

There has been a continued increase in the incidence of newly diagnosed melanomas, most of which are T1 melanomas.  It appears that after the institution of AJCC 7 (7th edition of the AJCC Cancer Staging Manual), there was an overall decrease in the number of T1 melanomas undergoing nodal biopsy without a clinically relevant change in sentinel lymph node positivity, with an increase in the number of T1b melanomas undergoing nodal evaluation.

Topographic Phenotypes of Alopecia Areata and Development of a Prognostic Prediction Model and Grading SystemA Cluster Analysis

The topographic characteristics of hair loss should be considered when assessing patients with alopecia areata for better prognostic prediction. In addition to extent of hair loss, temporal area involvement was independently associated with worse prognosis. Our grading system might aid clinicians in describing the extent and distribution of hair loss and predicting the prognosis. The TOAST(Topography-based Alopecia Areata Severity Tool) is an effective tool for describing the topographical characteristics and prognosis of hair loss and may enable clinicians to establish better treatment plans. Temporal area involvement should be independently measured for better prognostic stratification.

June 2019

Skin diseases of the breast and nipple: Benign and malignant tumors

• • The evaluation and management of dermatologic diseases of the breast and nipple require an understanding of the unique anatomy of the breast and nipple and an awareness of the significant emotional, cultural, and sexual considerations that may come into play when treating this anatomic area.
  • Review of breast anatomy, congenital breast anomalies, and benign and malignant breast tumors
  • An emphasis is placed on inflammatory breast cancer and breast cancer with noninflammatory skin involvement and on cutaneous metastases to the breast and from breast cancer.
  • Familiarity of the dermatologist with the cutaneous manifestations of breast cancer will facilitate the diagnosis of breast malignancy and assist with staging, prognostication, and evaluation for recurrence. T
  • Genodermatoses that predispose to breast pathology
  • Imaging recommendations for evaluating a palpable breast mass

Skin diseases of the breast and nipple: Inflammatory and infectious diseases

• • Certain dermatologic conditions are unique to the breast and nipple, whereas others may incidentally involve these structures.
  • All require a nuanced approach to diagnosis and treatment because of the functional, sexual, and aesthetic importance of this area.
  • The lactating patient requires special management because certain treatment options are contraindicated.
  • All dermatologic conditions involving the breast and nipple require careful evaluation because malignancy of the breast can be mistaken for a benign condition or may trigger the development of certain dermatologic conditions.
  • Common and uncommon inflammatory and infectious conditions of the breast and nipple
  • Conditions are divided into 4 distinct categories: 1) dermatitis; 2) radiation-induced changes; 3) mastitis; and 4) miscellaneous dermatologic conditions of the breast and nipple

Androgens in women: Androgen-mediated skin disease and patient evaluation

Androgen production and the relevant androgens

• • Androgens can be produced in the skin, but most circulating androgens are produced elsewhere
  • The major androgens in the serum of normoandrogenic women are (in descending order of serum concentration): dehydroepiandrosterone-sulfate, dehydroepiandrosterone, androstenedione, testosterone, and dihydrotestosterone
  • 5α-reductase converts testosterone into dihydrotestosterone, a most potent androgen

Androgen impact on sebaceous glands and hair

• • Androgen receptors are found in sebocytes, dermal papilla cells, the hair follicle outer root sheath, sweat glands, vascular endothelial and smooth muscle cells, and epidermal and follicular keratinocytes
  • Androgens can increase sebaceous gland proliferation and sebum production
  • Androgens cause hair follicle miniaturization along the frontal, centroparietal, and vertex scalp in genetically susceptible individuals as well as conversion of vellus to terminal hairs in other locations on the body

Androgen-mediated diseases of the skin

• • The pathogenesis of acne is complex and multifactorial; androgens promote sebum production, which plays a role in acne pathogenesis
  • While serum androgen levels are not correlated with acne presence or severity, local tissue androgen levels and sensitivity to androgens are important in acne pathogenesis
  • The distribution of acne is not a reliable predictor of a woman’s serum androgen profile

Hirsutism

• • Hirsutism is defined as excess terminal hairs in a male distribution (most commonly on the upper lip, areola, lower abdomen, and upper aspects of the thighs)
  • DHT promotes anagen phase and terminal hair development in areas other than the scalp
  • Most hirsute women have elevated serum androgen levels

FPHL

• • FPHL is characterized by scalp hair thinning over the crown, frontal, and temporal scalp, and its prevalence increases with age
  • In FPHL-prone regions of the scalp, androgens act on dermal papillae to transition terminal into vellus hairs, which is paradoxical to androgens’ effects on hair elsewhere in the body
  • The pathogenesis of FPHL is incompletely understood but is likely the consequence of genetically determined differences in androgen responsiveness

Androgens in women: Hormone-modulating therapies for skin disease

Androgen-modulating therapies used in dermatology

Combined oral contraceptives

• • Combined oral contraceptives contain estrogen and progestin, although the progestin component varies
  • While androgenic potential varies among progestins, the net effect of combined oral contraceptives is antiandrogenic
  • Combined oral contraceptive use is associated with an increased risk of venous thromboembolism, pulmonary embolism, myocardial infarction, stroke, and some cancers

Spironolactone

• • Spironolactone is a synthetic aldosterone receptor antagonist with mineralocorticoid and antiandrogen properties
  • Potassium monitoring is not necessary in healthy patients ≤50 years of age who are taking spironolactone and who do not have baseline renal dysfunction

Flutamide

• • Flutamide is a competitive antagonist of the androgen receptor
  • Flutamide is used off-label for the treatment of acne, hirsutism, and female pattern hair loss in women
  • Flutamide can be hepatotoxic and monitoring of liver function is recommended

Finasteride and dutasteride

• • Finasteride competitively inhibits 5α-reductase isoenzyme type II, and dutasteride irreversibly inhibits 5α-reductase isoenzymes types I and II
  • Finasteride and dutasteride are used off-label for the treatment of female pattern hair loss
  • Flutamide, dutasteride, and finasteride should not be used in women who are pregnant or who might become pregnant
  • Finasteride is used off-label for hirsutism

Hormone-modulating treatments for acne in women

• • Four COCs are approved by the US FDA for the treatment of acne in women also desiring contraception. Other COCs, spironolactone, and flutamide are used off-label for the treatment of acne
  • After 6 months of therapy, COCs are as effective as antibiotics for the treatment of acne. Practitioners may use COCs instead of antibiotics, given the concern for microbial resistance
  • There is a paucity of high-quality evidence demonstrating spironolactone’s superiority over placebo. Its use is based on consensus and expert opinion
  • Given the lack of evidence demonstrating its efficacy, flutamide is not commonly used in the treatment of acne

Hormone-modulating treatments for hirsutism in women

• • COCs are first-line therapy for the treatment of hirsutism in women with and without hyperandrogenemia
  • Spironolactone, finasteride, and flutamide are used off-label to treat hirsutism
  • When treating women of child-bearing potential, birth control (such as COCs) must be used in combination with spironolactone, finasteride, or flutamide in order to prevent pregnancy
  • Studies suggest that flutamide may be more effective than COCs for hirsutism, but it is not recommended as first-line therapy because of the risk of hepatotoxicity

Hormone-modulating treatments for FPHL

• • Spironolactone, finasteride, dutasteride, and flutamide are antiandrogens that are used off-label for FPHL
  • When treating women of child-bearing potential, birth control (such as COCs) must be used in combination with these medications to prevent pregnancy
  • Finasteride is used commonly for FPHL, but there is limited evidence supporting its efficacy
  • RCTs evaluating spironolactone, flutamide, and dutasteride for FPHL are lacking

The Use of Oral Antibiotics in the Management of Rosacea

Treatment of rosacea is challenging given the varied manifestations and incompletely understood etiology, but the treatment of papulopustular presentations often relies on oral antibiotics. Tetracyclines, specifically doxycycline, are the most commonly prescribed antibiotics for rosacea. Other antibiotics that can be used include macrolides, commonly azithromycin, and rarely, metronidazole. 

Safety and Effectiveness of Microfocused Ultrasound for Treating Erythematotelangiectatic Rosacea

The results of this study demonstrated that a single, high-density MFU-V treatment may be effective for treating erythematotelangiectatic rosacea. Based on these results, a large, randomized controlled study of single, high-density MFU-V treatment for erythematotelangiectatic rosacea is warranted.

Pharmacokinetic Profile, Safety, and Tolerability of Clascoterone (Cortexolone 17-alpha propionate, CB-03-01) Topical Cream, 1% in Subjects With Acne Vulgaris: An Open-Label Phase 2a Study

This study demonstrates the safety and tolerability of clascoterone topical cream, 1% in adolescents and adults with acne vulgaris treated BID for 14 consecutive days.

A Phase 2b, Randomized, Double-Blind Vehicle Controlled, Dose Escalation Study Evaluating Clascoterone 0.1%, 0.5%, and 1% Topical Cream in Subjects With Facial Acne

All clascoterone cream concentrations were well tolerated with no clinically relevant safety issues noted. Clascoterone 1% BID treatment had the most favorable results and was selected as the best candidate for further clinical study and development. Two Phase 3 investigations of clascoterone topical cream, 1% for the treatment of moderate-to-severe acne vulgaris in individuals ≥9 years recently concluded.

DNA Repair Enzyme Containing Lip Balm for the Treatment of Actinic Cheilitis: A Pilot Study

This study suggests that topical DNA repair enzyme lip balm containing T4 Endonuclease could potentially be a safe and efficacious way to improve and treat actinic cheilitis.

Arterial Occlusion and Necrosis Following Hyaluronic Acid Injection and a Review of the Literature

With the rising popularity of fillers for facial rejuvenation coupled with the paucity of regulations on credentialing of qualified injectors, the number of filler related complications is increasing. Although the majority of complications are mild, vascular occlusion is the most feared and dangerous. Minimizing risk of vascular complications through a comprehensive understanding of vascular anatomy and careful technique is important. Physicians who perform filler injections should also be able to promptly recognize complications and manage them. Vascular occlusion can be successfully managed using high dose hyaluronidase.

Evaluation of Prospective HLA-B*13:01 Screening to Prevent Dapsone Hypersensitivity Syndrome in Patients With Leprosy

Dapsone hypersensitivity syndrome (DHS) is the most serious adverse reaction associated with dapsone administration and one of the major causes of death in patients with leprosy, whose standard treatment includes multidrug therapy (MDT) with dapsone, rifampicin, and clofazimine. The HLA-B*13:01 polymorphism has been identified as the genetic determinant of DHS in the Chinese population. Prospective HLA-B*13:01 screening and subsequent elimination of dapsone from MDT for patients with HLA-B*13:01-positive leprosy may significantly reduce the incidence of DHS in the Chinese population.

Association of Ustekinumab vs TNF Inhibitor Therapy With Risk of Atrial Fibrillation and Cardiovascular Events in Patients With Psoriasis or Psoriatic Arthritis

The risks of atrial fibrillation and major adverse cardiovascular events associated with the use of ustekinumab vs TNF inhibitors were not different in patients with psoriasis or psoriatic arthritis; further investigations on potentially modifying treatment effects stratified by important risk factors may be warranted. No substantially different risk of incident AF or MACE after initiation of ustekinumab vs TNFi was observed in this study. This information may be helpful when weighing the risks and benefits of various systemic treatment strategies for psoriatic disease.

Association of HLA-C*06:02 Status With Differential Response to Ustekinumab in Patients With Psoriasis A Systematic Review and Meta-analysis

Previous research showed a differential response to ustekinumab therapy based on HLA-C*06:02 status in patients with psoriasis but consisted mostly of small (and sometimes inconclusive) cohort studies. The meta-analysis showed a differential response to ustekinumab therapy based on HLA-C*06:02 status in patients with psoriasis. Although HLA-C*06:02-positive patients had high PASI75 response rates after 6 months, the PASI75 response rate was also high in the HLA-C*06:02-negative group. Based on high PASI75 (75% improvement in Psoriasis Area and Severity Index) response rates in both genotype groups, there appears to be no rationale for excluding patients from ustekinumab treatment based on a negative HLA-C*06:02 status.

Did you enjoy this Journal Review Series? Find previous ones here.