Recurrent Pruritic Erythematous and Pigmented Plaques

Sarcoidosis can present with a wide variety of lesions and, given the strong family history, was considered in the clinical differential diagnosis. A biopsy of sarcoidosis lesions typically reveals granulomas composed of multiple histiocytes, which were not identified in our patient.^9,10 Bullous pemphigoid may begin with nummular lesions, but a biopsy typically reveals early blister formation. The necrotic keratinocytes evident in our case would not be characteristic of bullous pemphigoid. A biopsy for direct immunofluorescence reveals immunoglobulin G and C3 along the dermal epidermal junction.⁹ Lesions of urticaria are typically transient and do not last for longer than 24 hours. A biopsy of lesions of urticaria reveals edema and a perivascular infiltrate but wouldn’t have the epidermal changes noted on the biopsy results of our patient.⁹

Treatment and management. Initial lesions of fixed drug eruption often occur on the genitalia or the lips but can occur anywhere on the body surface. Lesions develop as late as 2 weeks after exposure to the inciting factor, so patients often fail to associate the eruption with a particular medication. Non-steroidal inflammatory medications, antibiotics, anticonvulsants, and allopurinol are common culprits.⁹ Identification and discontinuation of the offending chemical are critical to resolution.

Outcome and follow-up. Once the biopsy results established a diagnosis of fixed drug eruption, the patient was asked for a more detailed medication history. She noted that she was given fluconazole 150 mg which she took intermittently over the previous 6 months for repeated cutaneous candida infections. This was then determined to be the culprit for the fixed drug eruption. An oral methylprednisone acetate 4 mg 6-day dosepak was administered for maintenance and the patient's eruptions resolved over 6 months following the discontinuation of fluconazole. A follow-up was not required.  

Discussion. Fixed drug eruptions should be in the differential diagnosis whenever clinicians encounter an episodic eruption. Previous sites of involvement can become inflamed again, but new lesions may develop over time, so the eruption can be extensive at times.⁹ A biopsy can help to better characterize the eruption and to exclude similar clinical presentations.

A careful medical history is crucial in identifying the offending agent. Identifying the source can be difficult because the offending agent is usually taken or received intermittently, may be an over-the-counter medication (and therefore not considered a drug by the patient), and because most drug reactions are widespread and symmetric.

Fixed drug eruptions are considered a type of type IV delayed hypersensitivity reactions.⁹ Initial phase memory CD8+ cells release interferon after the offending agent damages the basal layer of the epidermis.¹¹ Patients can be reassured that lesions gradually fade after the inciting agent is stopped. 

While a typical case of fixed drug eruption, this case highlights the need to often go back and take a more detailed patient history. Periodic exposure to medications, environmental allergens, and other substances should be among the first question asked of patients presenting with a periodic eruption.

References

1. Blume JE, Ali L, Ehrlich M, Helm TN. Drug eruptions. Medscape. Updated July 7, 2022.  Accessed July 3, 2023. https://emedicine.medscape.com/article/1049474-overview
2. Temiz SA, Ozer I, Ataseven A, Findik S. A case of entecavir-associated bullous fixed drug eruption and a review of literature. Turk J Gastroenterol. 2019;30(3):299-302. doi:10.5152/tjg.2018.17887
3. Flowers H, Brodell R, Brents M, Wyatt JP. Fixed drug eruptions: presentation, diagnosis, and management. South Med J. 2014;107(11):724-7. doi:10.14423/SMJ.0000000000000195
4. Fukushima S, Kidou M, Ihn H. Fixed food eruption caused by cashew nut. Allergol Int. 2008;57(3):285-287. doi:10.2332/allergolint.C-07-58.
5. Cho YT, Lin JW, Chen YC et al. Generalized bullous fixed drug eruption is distinct from Stevens-Johnson syndrome/toxic epidermal necrolysis by immunohistopathological features.  J Am Acad Dermatol. 2014;70(3):539-48. doi:10.1016/j.jaad.2013.11.015
6. Shaker G, Mehendale T, De La Rosa C. Fixed drug eruption: an underrecognized cutaneous manifestation of a drug reaction in the primary care setting. Cureus. 2022;14(8):e28299. doi:10.7759/cureus.28299
7. Binns HM, Tasker F, Lewis FM. Drug eruptions and the vulva. Clin Exp Dermatol.  Published online October 31, 2023. doi:10.1093/ced/llad369
8. Mysorekar VV, Sumathy TK, Shyam Prasad AL. Role of direct immunofluorescence in dermatological disorders. Indian Dermatol Online J. 2015 May-Jun;6(3):172-80. doi:10.4103/2229-5178.156386.
9. Helm KF, Foulke GT, Marks JG. Differential diagnosis in dermatology. 2nd Ed. JP Medical Publishers, 2018.
10. Clarke LE, Clarke JT, Helm KF. Color atlas of differential diagnosis in dermatopathology. Jaypee Brothers Medical Publishers, 2014.
11. Shiohara T, Mizukawa Y. Fixed drug eruption: the dark side of activation of intraepidermal CD8+ T cells uniquely specialized to mediate protective immunity. Chem Immunol Allergy. 2012;97:106-121. doi:10.1159/000335623.

AFFILIATIONS:
¹Penn State Hershey Medical Center, Hershey, PA
²Buffalo Medical Group, PC, Department of Dermatology, Buffalo, NY

CITATION:
Helm TN, Tobias A, Albert S, Kalb RE. Recurrent pruritic erythematous and pigmented plaques: fixed drug eruption. Consultant. 2024;64(3):e1. doi:10.25270/con.2024.02.000002

Received September 12, 2023. Accepted December 15, 2023. Published online February 12, 2023.

DISCLOSURES:
The authors report no relevant financial relationships.

ACKNOWLEDGEMENTS:
None.

CORRESPONDENCE:
Thomas Helm, MD, 500 University Drive, Hershey, PA 17033 (thelm3@pennstatehealth.psu.edu)

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