Question

A gentleman in his 60s with PMH of HIV (CD4 178 on antiretroviral therapy), Hep C, Hep B, HTN, and prediabetes, was admitted for hypoglycemia and hypothermia after being found down. Dermatology was consulted for a diffuse pruritic, burning rash on the trunk and extremities for about 6 months. Medium potency topical corticosteroids provided partial relief of symptoms, but the patient described increasing number of pruritic plaques. Medication review showed amlodipine, lisinopril, trimethoprim/sulfamethoxazole, and metformin for his chronic medical conditions. Figures 1 and 2 demonstrate the pertinent skin findings.

Which of the following best describes the expected histopathology findings?

1. Compact orthokeratosis, lichenoid interface dermatitis, jagged rete ridges, eosinophilic remnants of keratinocytes in the epidermis
2. Dermis with marked inflammatory infiltrate of plasma cells around adnexal structures and vessels, irregular vascular spaces, hemosiderin deposition, and vessels wrapping pre-existing vessels
3. Lichenoid interface dermatitis with lymphocytic infiltrate deeper in the dermis, dermal melanin incontinence
4. Thin basket weave stratum corneum, vacuolar interface dermatitis with eosinophils and neutrophils, pigment incontinence in the papillary dermis
5. Neutrophils throughout the upper epidermis, with periodic acid–Schiff positive staining in the stratum corneum

Correct Answer

Correct Answer: D. Thin basket weave stratum corneum, vacuolar interface dermatitis with eosinophils and neutrophils, pigment incontinence in the papillary dermis

Explanation

With a CD4 count less than 200, this patient was newly taking trimethoprim/sulfamethoxazole for prophylaxis against pneumocystis pneumonia (PCP). The multiple, sharply demarcated, mostly circular and ovoid, thin, pigmented, pruritic plaques are most consistent with fixed drug eruption likely secondary to trimethoprim/sulfamethoxazole.

The characteristic histopathology findings for fixed drug eruption include the mismatch of an acute stratum corneum and the chronic changes of the superficial dermis. The interface dermatitis is more vacuolar rather than lichenoid with a diffuse band of inflammation obscuring the dermal-epidermal junction. Eosinophils and pigment incontinence are commonly seen (Choice D).¹ The histopathologic findings can be similar to erythema multiforme and graft-versus-host disease. However, both histopathologic differential diagnoses will typically have more necrotic keratinocytes.¹

While theoretically any medication can cause a fixed drug eruption, trimethoprim/sulfamethoxazole is a classic offender estimated to encompass the majority of cases.² In addition to the clinical morphology, dermatologists must be aware of common contexts for which classic offending medications may be prescribed. Tetracyclines are often implicated for fixed drug eruption on the penis, and pseudoephedrine is a common cause of the nonpigmented variant.² After the initial exposure, symptoms between a few days to a week is the typical time course. However, the symptoms can recur sooner and with more severity with repeated subsequent exposures.² After the appropriate diagnosis of fixed drug eruption, this patient’s PCP prophylaxis was switched to atovaquone, trimethoprim/sulfamethoxazole was added to his drug allergy list, and triamcinolone 0.1% ointment alleviated symptoms of pruritus.

Incorrect Options A. Describes histopathology of lichen planus,³ which would typically have clusters of smaller papules and plaques rather than the larger ovoid thin plaques seen with this patient. Drug-induced lichen planus/lichenoid drug eruption can be considered with multiple anti-hypertensives in the clinical history. Although histopathology can resemble typical lichen planus, the distinguishing feature can be the presence of increased eosinophils.

B. Describes histopathology of Kaposi sarcoma,³ which would be a reasonable morphological consideration in the setting of immunocompromise with a CD4 count <200. However, the multiple circular and ovoid plaques, in the context of a classic medication offender, are more likely fixed drug eruption, which was confirmed on biopsy for this patient. C. Describes histopathology of lichen planus pigmentosus,⁴ which would typically be more confluent and present more commonly on sun-exposed areas. E. Describes histopathology of tinea corporis, ³ which would typically appear more annular and ill-defined rather than so well-demarcated and homogenous throughout the plaque.

References

1. Elston DM. Chapter 7 – Interface dermatitis. In: Dermatopathology. 3rd Edition. Elsevier; 133-152. 2. Bergqvist C, Ingen-Housz-Oro S, and Chosidow O. Chapter 21 – Drug Reactions. In: Dermatology. 5th Edition. Elsevier; 355-384. 3. Elston DM. Dermatopathology. 3rd Edition. Elsevier. 4. Vega ME, Waxtein L, Arenas R, Hojyo T, Dominguez-Soto L. Ashy dermatosis and lichen planus pigmentosus: a clinicopathologic study of 31 cases. Int J Dermatol. 1992 Feb;31(2):90-4. PMID: 1559749.