Recurrent Fluconazole-Induced Fixed Drug Eruption of the Digit with Nail Matrix Involvement: A Case Report and Review of the Literature

Abstract

Introduction

Fixed drug eruptions (FDEs) are cutaneous hypersensitivity reactions due to an offending drug and are rarely associated with nail involvement. Moreover, FDEs associated with fluconazole use are sparsely reported in literature.

Case Presentation

We report a case of a recurrent FDE with involvement of one finger and corresponding Beau’s lines due to fluconazole use. The diagnosis of FDE secondary to fluconazole use was confirmed histopathologically, with improvement after the application of twice daily 0.05% clobetasol propionate ointment.

Conclusion

FDEs are hypersensitivity reactions that occur after exposure to an offending drug. FDEs uncommonly affect the nail matrix and are often not caused by fluconazole. It is important for dermatologists to assess for changes in the nail plate when evaluating a patient with FDE and evaluate all medications a patient is taking.

Established Facts

• •Fixed drug eruptions (FDEs) are cutaneous reactions that occur upon re-exposure of an offending drug.
• •FDEs commonly occur at the hands and feet, face, lips, and genitalia, with few reports describing nail involvement.

Novel Insights

• •We present the first case of a FDE induced by fluconazole with nail matrix involvement, as indicated by the development of Beau’s lines upon recurrent fluconazole use, indicating the cessation of mitotic activity at the nail matrix.

Introduction

Fixed drug eruptions (FDEs) are cutaneous delayed type IV hypersensitivity reactions that recur in the same location after exposure to an offending drug. They are attributed to the activation of CD8+ T-cells by drug antigens, resulting in the recruitment of neutrophils and additional T-cells which damage keratinocytes, melanocytes, and the basal layer of the epidermis [1].

Clinically, FDEs often present as well-demarcated red to violaceous patches or plaques which may blister or ulcerate. They are often asymptomatic but can sometimes present with pruritus or pain. FDEs commonly occur at the face, lips, hands, feet, and genitalia, rarely affecting the nail unit. Few reports have described FDEs presenting as acute paronychia or drug-induced changes in nail pigmentation [2–4]. Moreover, fluconazole is an uncommon cause of FDEs, with none of the reported cases of fluconazole-induced FDEs detailing the presence of nail involvement. We report a case of recurrent FDE presenting as circumferential erythema of the middle and distal phalanges of the left fourth digit and Beau’s lines of the nail plate in a patient taking oral fluconazole for treatment of vaginal candidiasis.

Case Presentation

A 30-year-old female presented to clinic for evaluation of a 1-day history of a pruritic, pink-colored rash on her left fourth digit with concomitant changes to the nail plate. She reported that this was the third time she noted these changes to her digit, with all three episodes occurring within 24 h of taking a single 150 mg dose of fluconazole for vaginal candidiasis. The first episode occurred approximately 6 months prior, where the patient was diagnosed with cellulitis of the digit and prescribed a 10-day course of doxycycline with no improvement. The second episode occurred approximately 4 months prior, where the patient was prescribed a 7-day course of valacyclovir 500 mg 3 times daily for presumptive herpetic whitlow. At our evaluation, she reported the development of pruritus and erythema of her left fourth digit, progressing to a peeling blister, within 24 h of taking oral fluconazole for an episode of vaginal candidiasis. She denied any other new medications, drug use, or medication allergies.

On physical examination, there was a well-demarcated, pink- to red-colored, edematous plaque with confluence circumferentially affecting the left fourth middle and distal phalanges (Fig. 1). Additionally, a transverse depression was noted at the proximal to mid-nail plate extending between both lateral nail folds (Fig. 2). No additional sites of involvement were noted by the patient upon exposure to oral fluconazole.

Fig. 1.

FDE at left fourth digit presenting as a well-circumscribed, red-colored plaque circumferentially affecting the middle and distal phalanges. FDE, fixed drug eruption.

Fig. 2.

Transverse depression at the proximal to mid-nail plate extending between both lateral nail folds, representing Beau’s line of the left fourth nail plate.

A 3 mm punch biopsy was performed of the left distal phalanx and the patient was prescribed clobetasol 0.05% ointment twice daily for application to the affected areas. Biopsy showed vacuolar alteration at the epidermal and dermal interface with sparse perivascular and superficial lymphocytic infiltrate (Fig. 3). Given these histopathologic findings and the patient’s recurrent cutaneous plaques after exposure to oral fluconazole, she was diagnosed with fluconazole-induced FDE. She was advised to discontinue further use of fluconazole and reported improvement with the twice daily application of 0.05% clobetasol propionate ointment.

Fig. 3.

Low- (a) and medium-power (b) photomicrograph showing vacuolar alteration at the dermal-epidermal interface (short arrows) and a sparse perivascular and superficial lymphocytic infiltrate (long arrows).

Discussion

Fluconazole is a triazole antifungal medication that is Food and Drug Administration (FDA)-approved for the treatment of vaginal, oropharyngeal, and esophageal candidiasis. Although tolerated by most patients, fluconazole can produce adverse effects such as gastrointestinal symptoms including abdominal pain, nausea, and vomiting, anaphylactic reactions, myalgia, fatigue, and hepatotoxicity. Cutaneous adverse reactions associated with fluconazole include exfoliative skin disorders such as Stevens-Johnson syndrome and toxic epidermal necrolysis, alopecia, acute generalized exanthematous pustulosis, and erythema multiforme [5–7]. It is uncommon for fluconazole to induce FDEs as there is sparse literature describing this entity [8–13]. Moreover, nail involvement has not been reported in patients with fluconazole-induced FDEs.

Our patient experienced recurrent digital cutaneous changes upon exposure to oral fluconazole for the treatment of vaginal candidiasis. Notably, our patient presented with a transverse depression at the nail plate, consistent with Beau’s lines that occurred each time the patient began a new course of fluconazole. Beau’s lines signify a transient cessation of nail matrix growth. This cessation of mitotic activity manifests itself clinically as a transverse depression of the nail plate. Upon removal of the offending agent, mitotic activity resumes and the transverse line progresses as the nail plate extends. The depth and length of the Beau’s lines offer clinical value as the amount of matrix damage and insult duration time are directly correlated with these metrics, respectively. In our patient’s case, the development of Beau’s lines coincided with oral fluconazole use and is attributed to a FDE secondary to recurrent fluconazole use.

Conclusion

Herein, we report a case of recurrent fluconazole-induced FDE with nail matrix involvement as evident by the presence of Beau’s lines. This case is unusual in that FDEs are rarely associated with nail involvement [2, 3]. Thus, it is important for dermatologists to assess for changes in the nail plate when evaluating a patient with FDE. As FDEs recur upon re-exposure to an offending drug and may even become more extensive, it is vital to recognize this entity and promptly cease the offending medication.

Statement of Ethics

Written informed consent has been obtained from the patient for publication of the details of their medical case and any accompanying images. Ethical approval is not required for this study in accordance with local or national guidelines.

Conflict of Interest Statement

Loren E. Hernandez, Arvin Jadoo, and Brian Morrison have no conflicts of interest to disclose.

Funding Sources

Loren E. Hernandez, Arvin Jadoo, and Brian Morrison have no funding to disclose.

Author Contributions

Loren E. Hernandez, Arvin Jadoo, and Brian Morrison took part in the care of the patient, wrote, revised, and approved this manuscript for submission to Skin Appendage Disorders.

Funding Statement

Loren E. Hernandez, Arvin Jadoo, and Brian Morrison have no funding to disclose.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.