Generalized fixed drug eruptions in skin of color

What is known about this subject in regard to women and their families?

• Generalized fixed drug eruptions are rarely reported in the literature, particularly in women of color, who may experience a significant diagnostic delay.

What is new from this article as messages for women and their families?

• Generalized fixed drug eruptions affect women of color, and this diagnosis should be considered in patients who have recurrent and fixed hyperpigmented, but not erythematous lesions.

Fixed drug eruption (FDE) is an uncommon mucocutaneous medication reaction that often presents with ovoid erythematous-to-violaceous patches or plaques.¹ Lesions may recur at the same site within hours of re-exposure to offending medications. FDE often manifests as a single lesion; however, multiple lesions may present on noncontiguous body sites, representing generalized FDE (GFDE).¹ FDE may be a clinical diagnosis, but supporting histopathology demonstrates interface dermatitis with melanophages and eosinophils. FDE and GFDE are not commonly reported in patients with skin of color (SOC). In this case series, we present a female-majority SOC patient cohort with GFDE previously misdiagnosed as inflammatory or infectious dermatoses.

Five patients (4 female, 1 male) were independently referred to the dermatology clinic for further evaluation of rashes. All patients reported pruritic, darkly pigmented areas on multiple sites that waxed and waned but otherwise recurred in the same locations. Patients had been diagnosed with chronic urticaria, sarcoidosis, bullous pemphigoid, eczema, and tinea corporis based on history and physical examination by nondermatologists before establishing with our clinic. GFDE was suspected in each patient, based on the presence of well-demarcated violaceous and/or hyperpigmented plaques that recurred in the same noncontiguous body sites. The differential diagnosis could have also included lichen planus pigmentosus or erythema multiforme in some cases. Biopsy was performed in each case, all demonstrating interface dermatitis with eosinophils and melanophages, consistent with FDE, and GFDE was diagnosed. Patients 1, 2, 3, and 4 had added a new medication to their regimen before rash onset, presumed to be the culprit medication. These 4 patients were women, and their GFDE had been ongoing for at least 6 months, and in some cases, more than 1 year. Patient 5’s lesions appeared during hospitalization weeks prior after multiple medication exposures. A culprit medication was not identified for patient 5. Representative lesions are shown in Figure 1. Patient demographics, lesion distribution, misdiagnoses, and GFDE culprit medications are summarized in Table 1.

Fig. 1.

Representative images of generalized fixed drug eruption lesions from patients presented in Table 1, demonstrating variable degrees of hyperpigmentation and violaceous hues across different lesion sizes and locations. Representative lesions include smaller ovoid hyperpigmented violaceous papules to the arm (patient 1, A), larger hyperpigmented plaques with erythematous borders to the leg (patient 1, B), linearly arranged hyperpigmented papules with induration and erythema to the outer arm (patient 1, C) ovoid hyperpigmented papules to the temple (patient 2, D), hyperpigmented rounded plaques to the neck (patient 3, E), wrist (patient 3, F), dorsal foot (patient 3, G), and back (patient 4, H), and hyperpigmented rounded plaques with violaceous borders to the legs (Patient 5, I).

Table 1.

Summary of patient demographics, including race (self-reported), and clinical presentation of generalized fixed drug eruption (GFDE) lesions, prior treatments for previous misdiagnoses and identified culprit medication for the patient’s GFDE

Patient	Age	Race	Sex	Location of lesions	Reported symptoms of lesions	Prior treatments	Previous Diagnosis	Culprit Medication
1	51	African American	Female	Upper and lower extremities	Pruritus, rough texture	Hydrocortisone 2.5% cream, antihistamines	Chronic urticaria	Ibuprofen
2	49	African American	Female	Face, neck, chest, upper extremities	Pruritus and burning	Emollient	Sarcoidosis	Ertugiflozin
3	45	African American	Female	Hard palate, upper and lower extremities	Pruritus and blistering	Prednisone, doxycycline 100 mg	Bullous pemphigoid	Oral contraceptives
4	57	Caribbean	Female	Abdomen, upper and lower extremities	Pruritus and rough texture	Triamcinolone 0.1% cream	Eczema, xerosis	Aspirin
5	75	African American	Male	Abdomen, lower extremities	Pruritus and rough texture	1% clotrimazole cream, neosporin, and hydrogen peroxide	Tinea corporis	Unknown

Only patient 3 had mucosal involvement, and no patients had genital involvement or abnormal nail findings.

FDEs classically present as round, erythematous patches and plaques in lighter skin tones, and they may develop dusky or purple shades as they resolve. FDE may appear differently in individuals with SOC, often presenting with prominent hyperpigmentation.² Additionally, erythema in SOC will often appear violaceous.³ In this case series of 5 SOC GFDE patients, most of whom are women and had diagnostic delays of at least 6 months, all patients presented with prominent lesional hyperpigmentation, with varying degrees of violaceous hues, contrasting to the classic erythematous and nonpigmented lesions seen in lighter skin tones. Even in patients with minimal violaceous coloring and more predominant hyperpigmentation (patients 3 and 4), histopathology still demonstrated an active inflammatory process. Management of FDEs includes identification and withdrawal of the culprit medication. Topical steroids and antihistamines can be used for symptomatic management while lesions resolve, and most patients do not require additional treatment unless re-exposure occurs. However, postinflammatory hyperpigmentation can persist for prolonged periods of time, and this may also be more apparent in SOC populations.

Attention has been paid to the lack of SOC representation in medical learning resources, textbooks, and high-impact dermatology journals.⁴ As dermatology is a highly visual field and relies on pattern recognition, exposure to inflammatory dermatoses in SOC is essential for accurate diagnoses in practice. Compounding the potential lack of awareness is the fact that SOC patients may be less likely to receive outpatient dermatology care, likely contributing to a lack of accurate and timely diagnosis.⁵ We present this case series to highlight the disparity that SOC women presenting with GFDE may experience and to expand the differential diagnosis of multiple hyperpigmented lesions in SOC.

Conflicts of interest

None.

Funding

None.

Study approval

This study was approved by Roswell Park IRB (Study 2486).

Author contribution

DK: Participated in research design. AG and DK: Participated in data collection. AG, SP, and DK: Participated in data analysis and writing of the paper.

Patient consent

Consent for the publication of all patient photographs and medical information was provided by the authors at the time of article submission to the journal, stating that all patients gave consent for their photographs and medical information to be published in print and online, and with the understanding that this information may be publicly available.