Literature Lessons

By Ted Rosen, MD, FAAD, Editor-in-Chief

Off-label pearl

Metformin: a cheap, relatively safe medication
Metformin, either as a stand-alone or as part of a regimen, is beneficial in women with polycystic ovary syndrome (PCOS) who have acne. Dosage required may vary from 500 mg QD to 500 mg TID. This recommendation is based on a meta-analysis including 51 studies and 2405 patients.
TO READ MORE: Yen H, et al. Metformin therapy for acne in patients with polycystic ovary syndrome: a systematic review and meta-analysis. Am J Clin Dermatol. 2020;Oct 13. DOI: 10.1007/s40257-020-00565-5

Metformin has also been described as beneficial for patients with hidradenitis suppurativa. This recommendation is based on a recent study of 53 patients (85% female) who took a mean dose of 1.5 g/day during a follow-up period of just under a year and showed a 68% rate of subjective response.
TO READ MORE: Jennings L, et al. Metformin use in hidradenitis suppurativa. J Dermatolog Treat. 2020;31(3):261-263.

Rheumatologic diseases

Many inflammatory diseases are co-managed by dermatologists and
rheumatologists. Beware the increasing trend toward NON-MEDICAL
SWITCHING BY INSURANCE CARRIERS. For example, beginning
January 1, 2021, patients who use the Express Scripts formulary will
be forced to switch from secukinumab to ixekizumab, regardless of
whether or not they or their doctor agree with this change.

Hair and nails

Cases of TELOGEN EFFLUVIUM have increased since the onset of the COVID-19 pandemic. It is theorized that this may be associated with increased stress, anxiety, and sleep disturbance.
TO READ MORE: Xerfan EMS, et al. The role of sleep in telogen effluvium and trichodynia: a commentary in the context of the current pandemic. J Cosmet Dermatol. 2021;Jan 2. doi: 10.1111/jocd.13929

Contact dermatitis

Contact dermatitis related to MINOXIDIL use for androgenetic alopecia is usually due to a solvent constituent of the product. However, it can be due to hypersensitivity to the minoxidil itself, as documented in this report. Patch testing is accomplished with pure minoxidil powder provided by the manufacturer.
TO READ MORE: Nagarajan H, Rai R. Contact dermatitis to minoxidil. Contact Dermatitis. 2021;84(1):57.

EFINACONAZOLE AND LULICONAZOLE are relatively recent introductions to the American anti-fungal armamentarium. Although considered quite rare, acute contact dermatitis has been documented to occur due to hypersensitivity to both agents.
TO READ MORE: Fujimoto K, et al. Contact dermatitis caused by efinaconazole and luliconazole. J Nippon Med Sch. 2020 Aug 31. doi: 10.1272/jnms.JNMS.2021_88-312

Atopic dermatitis

Although much more work remains to be done to determine optimal
formulations and usage patterns, a small observational study indicated
that TOPICAL CANNABINOIDS hold promise in the management of atopic dermatitis and other eczematous states.
TO READ MORE: Maghfour J, et al. An observational study of the application of a topical cannabinoid gel on sensitive dry skin. J Drugs Dermatol. 2020;19(12): 1204-1208.

Psoriasis

Triggers for flares of PEDIATRIC PSORIASIS include infections, emotional stress, and cigarette smoke exposure.
TO READ MORE: Pithadia DJ, et al. Translating the 2019 AAD-NPF guidelines of care for the management of psoriasis in pediatric patients. Cutis. 2020;106:257-260.

A very small American prospective study indicates that APREMILAST THERAPY may improve signs and symptoms of nail psoriasis. Thirty mg apremilast BID led to a 75% decrease in mNAPSI scores (objective measurement of nail psoriasis severity). Oak A. EADV Congress, Oct 2020.

Due to exclusion of PREGNANT WOMEN and inadequate identification of pregnancies in registry data, little reliable information exists to guide treatment of psoriasis during pregnancy. In general, limited non-occluded use of topical steroids, UVB phototherapy, and administration of TNF-alfa inhibitors are considered “reasonable.”
TO READ MORE: Flood KS, et al. Treatment of psoriasis in pregnancy. Cutis. 2020;106(S2):15-20.

A prospective German study suggested that SUBCUTANEOUS METHOTREXATE has a faster onset and a higher PASI 90 outcome compared
to oral methotrexate.
TO READ MORE: Reich K, et al. The value of subcutaneous vs oral methotrexate: real-world data from the German psoriasis registry psoBest. Br J Dermatol. 2020 Nov 21. doi: 10.1111/bjd.1969

Although yearly testing for TUBERCULOSIS is a standard protocol when administering biological drugs, the actual rate of conversion is quite low,
when considering some classes. For example, a recent pooled cohort study of 28 secukinumab trials disclosed latent tuberculosis appearance in 0.1% of 12,319 subjects.

TO READ MORE: Elewski BE: Association of secukinumab treatment with tuberculosis reactivation in patients with psoriasis, psoriatic arthritis or
ankylosing spondylitis. JAMA Dermatol. 2021;157:43-51.

General dermatology

DELUSIONAL PARASITOSIS can be effectively treated with low-dose pimozide (3 mg or less daily). Such a low dose may only rarely be associated with the dreaded complication of tardive dyskinesia. After symptom resolution, the drug can often be tapered and then stopped without recurrence.
TO READ MORE: Brownstone ND, Koo J. Recent developments in psychodermatology and psychopharmacology for delusional patients. Cutis. 2021;107:5-6.

Dermatologists should be aware that chronic use or covert ABUSE OF OPIOIDS may result in generalized pruritus. Abuse of cocaine or amphetamines may result in crawling sensations under the skin, resembling delusional parasitosis. Due to overlapping pathways, both addiction and pruritus may be perpetuated in parallel.
TO READ MORE: Lipman ZM, Yosipovitch G. Substance use disorders and chronic itch. J Am Acad Dermatol. 2021;84:148-55.

Along with tattoos and body piercings, incarcerated individuals may create multiple subcutaneous penile nodules called “SPEED HUMPS.” Various small objects are formed into a smoothed sphere, and then inserted through a self-made superficial incision in the penile shaft. This practice allegedly enhances sexual pleasure for partners.
TO READ MORE: Chateau AV, et al. Penile nodules in prisoners. Int J Dermatol. 2020;59:1520-21.

Perhaps not too surprisingly, a study of 62 patients with HAND ECZEMA disclosed that almost 68% of them suffered from significant stress, suggesting that stress management should be an important part of their therapeutic regimen. Stress was assessed using the validated Perceived Stress Scale questionnaire.
TO READ MORE: Janardhanan AK, et al. Therapeutic considerations related to stress levels associated with hand eczema: a clinico-etiological study. Dermatol Ther. 2020;33(6):e14508. doi: 10.1111/dth.14508

FACIAL ANGIOFIBROMAS associated with tuberous sclerosis can be successfully managed by sequential surgical debulking followed by long-term application of topical rapamycin (sirolimus).
TO READ MORE: Patterson JL, et al. Combined treatment of disfiguring facial angiofibromas in tuberous sclerosis complex with surgical debulking and topical sirolimus. Cutis. 2020;106(6):307-308.

Apparently, many college students have not gotten the message about PHOTOPROTECTION. A sample of 673 collegiates disclosed that only 9.5% used sunscreen and 12.6% used tanning beds, the latter being particularly common in the winter.
TO READ MORE: Graham EM, Merrill KC. Sunscreen and tanning bed use in high-risk college-aged students. JDNA. 2020;12(6):286-92.

A recent online study of a nationally representative sample (N=705) of American men showed that 83% REPORTED NOT USING SUNSCREEN DAILY,
and only 38% USED SUNSCREEN AT LEAST WEEKLY.
Yearly income over $100,000 correlated with greater degree of sunscreen use.
TO READ MORE: Roberts CA. Men’s attitudes and behaviors about skincare and sunscreen use. J Drugs Dermatol. 2021;20:88-93.

Drugs and devices

Suicidal ideation, attempted suicide, and completed suicide are more common among men aged 18-44 when they are taking FINASTERIDE
FOR ALOPECIA, compared to a matched cohort not taking finasteride.
Whether this is directly related to the drug or a manifestation of psychological abnormality due to the alopecia is uncertain.
TO READ MORE: Nguyen DD, et al. Investigation of suicidality and
psychological adverse events in patients treated with finasteride. JAMA
Dermatol
. 2020 Nov 11:e203385. doi: 10.1001/ jamadermatol. 2020.3385

Hidradentitis suppurativa

The perfect storm of increasingly prevalent childhood obesity, lowered pubertal age, and better awareness of HS may lead to this diagnosis in ADOLESCENCE AND CHILDHOOD. Treatments are largely extrapolated from the adult experience with several caveats. Doxycycline is the preferred tetracycline agent due to lowered risk of tooth discoloration, and use of finasteride is uncertain with regard to eventual prostate size, sexual dysfunction, and pubertal development.
TO READ MORE: Choi E, et al. Hidradenitis suppurativa in pediatric patients. J Am Acad Dermatol. 2020 Aug 18. doi: 10.1016/j.jaad.2020.08.045

If your hidradenitis patients go to an EMERGENCY DEPARTMENT,
they are likely to receive prescriptions for opioid narcotics (58.3%) and non-tetracycline antibiotics (66.6%). This information was based on a retrospective analysis of National Hospital Ambulatory Medical
Care Survey data from 2006-2017.

TO READ MORE: Taylor MT, et al. Pain severity and management of
hidradenitis supprativa at US Emergency Department visits. JAMA Dermatol. 2021;157:115-117
.

Cutaneous oncology, surgery, and lasers

Sophisticated population modeling done in Australia demonstrated that, for individuals 50 years of age and older followed for the next 30 years, primary prevention (sunscreen and appropriate physical cover) was the most effective method of reducing both MELANOMA AND NON-MELANOMA SKIN CANCER. Preventative measures were more effective than utilizing early detection techniques, such as periodic skin examinations.
TO READ MORE: Gordon L. Prevention versus early detection for long-term control of melanoma and keratinocyte carcinomas: a cost-effectiveness modelling study. BMJ Open. 2020 Feb 26;10(2):e034388. doi: 10.1136/bmjopen-2019-034388

ERYTHEMA AB IGNE, considered a pigmentary response, occurs following protracted exposure to infrared heat at temperatures insufficient to cause a burn. As illustrated by this case report, erythema ab igne can progress
to develop cutaneous squamous cell carcinoma.
TO READ MORE: Wilder EG, et al. Erythema ab igne and malignant transformation to squamous cell carcinoma. Cutis. 2021;107:51-53.

A retrospective analysis of nearly 109,000 IN SITU AND INVASIVE MELANOMAS derived from the National Cancer Database demonstrated no overall survival difference between lesions on the trunk, upper extremity,
or lower extremity, regardless of treatment modality (wide local excision vs Mohs micrographic surgery). The mean age at diagnosis of individuals included in this analysis was 58.8, and 52.7% were male.
TO READ MORE: Demer AM, et al. Association of mohs micrographic surgery vs wide local excision with overall survival outcomes for patients with melanoma of the trunk and extremities. JAMA Dermatol. 2021;157:84-89.

Rosacea

A meta-analysis of 13 studies, encompassing more than 50,000 patients, demonstrated an association between rosacea and HYPERTENSION AND
DYSLIPIDEMIA. Conversely, rosacea was not associated with ischemic heart
disease, stroke, or diabetes.
TO READ MORE: Chen Q, et al. Association between rosacea and cardiometabolic disease: a systematic review and meta-analysis. J Am Acad Dermatol. 2020;83(5):1331-1340.

OCULAR ROSACEA is a chronic inflammatory process which can lead to visual defect and even blindness. Chronic maintenance therapy is often indicated to prevent periodic flares. Topical low-potency steroids and cyclosporine, as well as oral tetracycline derivatives, are mainstays of therapy. However, there is a critical lack of well-done randomized, controlled studies to define optimal interventions.


TO READ MORE: Redd T, Seitzman GD. Ocular rosacea. Curr Opin Ophthalmol. 2020;31(6):503-507.

Acne

A case report described the efficacy of the recently approved narrow-spectrum antibiotic sarecycline for PERIORAL DERMATITIS. This usage is off-label.
TO READ MORE: Graber E, Kay CRS. Successful treatment of periorificial dermatitis with novel narrow spectrum sarecycline. J Drugs Dermatol. 2021;20:98-1000.

A large-scale retrospective study spanning 10 years (2008-2018) indicated that the proportion of dermatologists who routinely performed SERUM POTASSIUM TESTING on young adult women being treated for acne with spironolactone was low and decreasing. This is consonant with increasing evidence that potassium monitoring is not needed in this situation.
TO READ MORE: Barbieri JS, et al. Temporal trends and clinician variability in potassium monitoring of healthy young women treated for acne with
spironolactone. JAMA Dermatol. 2021; January 27. doi:10.1001/jamadermatol.2020.5468

Cosmetic dermatology

BLACK HENNA TATTOOS are often contaminated with para-phenylenediamine, thereby leading contact dermatitis of variable severity. Black henna tattoos and the contaminant can be easily removed in a single session consisting of repeated rinsing of the skin with polyethylene glycol 400 solution. A maximum of 6 rinse cycles was required to effect this removal.
TO READ MORE: Ferrari DM, et al. Efficient removal of black henna tattoos. Pediatr Dermatol. 2020;37:1063-67.

Infectious diseases

In a longitudinal study of 6515 HIV-positive individuals, ANAL CARCINOMA was 12.79 times more likely to occur when there was a present or past history of anogenital warts. Anal cancer developed in 4.4% of those with a history of anogenital warts compared to 0.3% of thse who did not have a history of anogenital warts.
TO READ MORE: Arnold JD, et al. The risk of anal carcinoma after anogenital warts in adults living with HIV. JAMA Dermatol. 2021, January 13. doi: 10.1001/jamadermatol.2020.5252

Although TOPICAL CICLOPIROX has the lowest relative cure rate, it remains the most commonly prescribed onychomycosis therapy among all groups of health care providers, including dermatologists and podiatrists.
TO READ MORE: Yang EJ and Lipner SR. Prescribing patterns of onychomycosis therapies in the United States. Cutis. 2020;106(6):326-327.

RECALCITRANT DERMATOPHYTOSIS may be due to inherent antifungal resistance, skin barrier disruption, reinfection from clothes or the environment, and ambient factors (heat/humidity). Recalcitrant dermatophytosis may be treated by homologous autoimplantation.
The latter technique introduces tiny bits of fungal-infected skin
into the patient’s subcutaneous tissue, in order to stimulate a
vigorous immune response. Clearance may be expected in about 3 months.
TO READ MORE: Kumar, S, et al. Autoimplantation therapy in extensive and recalcitrant dermatophytosis: a case series. J Clin Aesthet Dermatol. 2021;14:34-37.

A standardized 0.7% viscous investigational cantharadin product (VP-102) was applied to all MOLLUSCUM CONTAGIOSUM every 21 days for a maximum of 4 times. Plasma cantharidin concentrations were below the lower limits of quantification (2.5 ng/mL). Analysis of 32 ITT subjects showed a mean decrease in lesions by the end of the study (day 84).
TO READ MORE: Niazi S, et al. A Phase 2 open-label study to evaluate VP-102 for the treatment of molluscum contagiosum. J Drugs Dermatol. 2021;20:70-75.

Pediatric dermatology

Mothers of children with PSORIASIS more often suffer from depression (14 of 60) than mothers of age/sex matched control children being followed for multiple nevi (3 of 60). Mothers of children suffering from psoriasis achieved significantly higher scores in the Beck Depression Inventory questionnaire when compared to mothers in the control group (7.3 ± 6.91 points vs 2.75 ± 3.46 points, respectively; P = .000005).
TO READ MORE: Žychowska M. Depressive symptoms among mothers of children with psoriasis—A case-control study. Pediatr Dermatol. 2020;37:1038-43.

A small study demonstrated the feasibility and efficacy (80% cure) of using topical encapsulated 1% terbinafine, twice daily for 4 weeks, in the treatment of pediatric TINEA CAPITIS. Further study is needed to verify and commercialize such a product, but the technology is available.
TO READ MORE: Jerasutus S, et al. Treatment of tinea capitis with topical 1% encapsulated terbinafine hydrochloride gel: a pilot study. Pediatr Dermatol. 2020;37:1090-93.