Erythematous papules on face and torso

Case #1There are three major varieties of eosinophilic folliculitis: classic eosinophilic pustular folliculitis (EPF; Ofuji disease), eosinophilic pustular folliculitis in infancy, and human immunodeficiency virus (HIV)- or immunosuppression-associated eosinophilic folliculitis (HEF). These conditions are rare, and HEF typically occurs in...

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Case #1

There are three major varieties of eosinophilic folliculitis: classic eosinophilic pustular folliculitis (EPF; Ofuji disease), eosinophilic pustular folliculitis in infancy, and human immunodeficiency virus (HIV)- or immunosuppression-associated eosinophilic folliculitis (HEF). These conditions are rare, and HEF typically occurs in HIV-infected adults with CD4 counts of less than 300 cells/mm³, but is also seen in patients with lymphoma, chronic lymphocytic leukemia, acute myelogenous leukemia, and myeloproliferative disorders.¹ Patients who have received allogeneic hematopoietic stem cell transplantation are also at risk.^2,3

Although the exact pathogenesis of HEF remains unknown, some studies have reported a Th2 pattern with elevated levels of interleukin (IL)-4, IL-5 and chemokines RANTES (regulated on activation normal T cell expressed and secreted) and eotaxin messenger RNA within lesions.^1,4 The mite Demodex folliculorum has been implicated in the pathogenesis of HEF due to an abnormal immune response to the mite as an antigen, but some studies propose that they are separate entities.³

Papular follicular eruptions on acne-prone areas, such as the face, scalp, and upper trunk characterize HEF. The papules are chronic, recurrent, erythematous, and often intensely pruritic, but they may or may not present with pustules.^1,3,6 There are reports of HEF as the presenting feature of HIV infection.⁶

HEF is different from EPF in that the papules do not coalesce into plaques or form annular lesions and the individual lesions are more persistent.^3,6 The differential diagnosis includes more common causes of erythematous papules, such as acne vulgaris and folliculitis, both bacterial and fungal. Less common causes of folliculitis that could be included in the differential diagnosis include herpes simplex folliculitis, pseudofolliculitis barbae, actinic folliculitis, drug-induced folliculitis, and Demodex folliculitis. Lupus miliaris disseminatus faciei, rosacea, granuloma faciale, drug-induced folliculitis, and graft-versus-host disease after bone marrow transplantation can also be considered. Given their clinical similarities, microscopic examination of follicular contents, as well as punch biopsy, provide a definitive final diagnosis. If the patient has not been tested recently, HIV testing is recommended.^1,3,7 Another papular and pruritic dermatosis related to HIV infection is HIV-related pruritic papular eruption (or prurigo). It can present as an eruption clinically similar to HEF but can be differentiated by histopathology and immunohistochemical staining. HEF has a denser perivascular and diffuse inflammatory infiltrate, with high expression of eosinophils and mast cells.⁸ 

Histologically, HEF is similar to EPF, but EPF always involves the infundibular region of hair follicles, whereas HEF may only have perifollicular infiltrates. Biopsy of involved follicles in HEF exhibits spongiosis and exocytosis of lymphocytes and eosinophils into the follicular epithelium. A dermal infiltrate of lymphocytes and eosinophils may also be present. Micropustular aggregation may lead to eosinophilic pustules and occasional follicular mucinosis and abscess formation. CD8+ lymphocytes predominate in HEF.^1,3,7

No treatment has been uniformly effective for HEF, but management of the underlying disease process, such as HIV, is paramount.^1,3 A rise in the CD4 count may lead to resolution of HEF, but eruptions can also be seen in the first 3 to 6 months of antiretroviral therapy with immune reconstitution.⁷ Oral and topical therapies that are effective in some cases, such as antipruritic agents, indomethacin, and topical steroids, may be inadequate in individuals with other diseases causing immunosuppression or in those who have already failed antiretroviral therapy. Ultraviolet B phototherapy may be curative in such cases. Other topical therapies to consider include tacrolimus and permethrin. Oral therapies cited in the literature include itraconazole (100-400 mg/d), antibiotics, isotretinoin (0.5-1 mg/kg/d × 1-4 wk, then taper), and interferon (beta and gamma).^1,3

In our case, punch biopsy confirmed eosinophilic folliculitis in the patient, and the patient tested positive for HIV (CD4<300 cells/mm³). He was referred to the infectious disease department to begin antiretroviral therapy.

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Case #2 

Various drugs have been implicated in causing acne or eruptive acneiform lesions as a side effect of their use. High-dose intravenous or oral corticosteroids are the most common medications implicated in acneiform eruptions that concentrate on the chest and back. Steroid-induced acne (and rosacea) can also result from inappropriate use of topical corticosteroids on the face or after chronic inhalation of steroid-containing medications.^1,9,10

Perioral dermatitis, which predominantly affects women, is seen in patients using inhaled and topical corticosteroids for long durations.^10,11 Misuse of topical corticosteroids is a widespread cause of acne and telangiectasia, especially among young women worldwide, many of whom view these medications as skin-lightening agents.¹²

The exact pathogenesis of how corticosteroids cause acneiform eruptions remains unclear because they are anti-inflammatory agents. However, studies have found that dexamethasone and cortisol added to cultured human keratinocytes promote cellular toll-like receptor 2 (TLR2) expression. This increases TLR2’s probability of activation to circulating inflammatory cytokines or to Propionibacterium acnes, the bacteria found in normal skin flora and the most common culprit in classic acne vulgaris. In this context, these drugs may trigger proinflammatory changes in the skin when used incorrectly or for long durations.¹³

Inflamed, dome-shaped papules and pustules develop on a background of erythema that tends to follow the distribution of corticosteroid application, or they appear on the upper arms and trunk weeks to months after beginning a systemic regimen. The differential diagnosis of steroid-induced acne includes eruptions caused by other medications, acne vulgaris, and folliculitis (including eosinophilic, bacterial, and fungal). Unlike acne vulgaris and acne caused by cosmetics or friction, comedones are typically absent in drug-induced acne, perioral dermatitis, and rosacea.¹⁰ To rule out acne caused by other medications, an understanding of when medications were initiated in relation to symptom onset is necessary.

Other agents commonly known to cause drug-induced acneiform eruptions include corticotropin, androgens and anabolic steroids, bromides, iodides, isoniazid, lithium, phenytoin, and progestins. Targeted therapies, such as tyrosine kinase inhibitors, monoclonal antibodies, soluble receptors (etanercept), transcription modulators, and proteasome inhibitors, have also been implicated. A thorough medical history is thus indicated for any atypical, nonjuvenile-onset cases of acne or acneiform eruptions.^1,9,10 In women, misuse of anabolic androgenic steroids causes hirsutism and deepening of the voice, in addition to acne.¹⁴

Histopathologic findings of classic acne lesions reflect the stage of the lesion and clinical findings. In acne vulgaris, microcomedones show keratinocytes plugging the opening to a distended follicle; closed comedones exhibit increased follicular distension due to the cystic structure, with eosinophilic keratin debris, hair, and bacteria. As the follicular epithelium distends due to the increasing infiltrates and disruption of the pilosebaceous unit, the obstructing contents can rupture into the dermis. The keratin, hair, and bacteria provoke a strong inflammatory response, with neutrophils forming pustules leading to eventual granulomatous changes and scarring.¹ Perioral dermatitis, however, exhibits histopathologic features similar to those of rosacea: lymphocytes and histiocytes around follicles and their vascular supply with concurrent sebaceous hyperplasia.¹¹

“Steroid acne” and “steroid-induced acne” are misnomers in that these drugs do not cause a true form of acne and can be differentiated histologically. Their histopathology resembles folliculitis with neutrophils surrounding the hair follicle. Drug-induced acne presents abruptly as a monomorphic, inflammatory papular and pustular eruption, unlike the heterogeneous and more common lesions of acne vulgaris. Some physicians therefore refer to drug-induced acne as a form of folliculitis.^1,9,10 Eosinophilic folliculitis exhibits eosinophils and lymphocytes rather than neutrophils around the hair follicle; unlike bacterial or fungal folliculitis, steroid use in the past few days to weeks would establish a likely diagnosis of steroid-induced acne.

Endothelial growth factor receptor inhibitors (EGFRIs) have also been shown to cause acneiform eruptions in a high proportion of patients on these drugs. This class includes gefitinib, cetuximab, erlotinib, lapatinib, and panitumumab. Monomorphic, follicular pustules and papules erupt on the face, scalp, and trunk 1 to 3 weeks after initiation of the EGFRI. Coinfection with Staphylococcus aureus may occur, causing discharge and honey-colored crusting and scale. Histopathology in these cases shows a folliculitis pattern, including neutrophils within the follicle and lymphocytes aggregated around it.^9,10 Medication history and biopsy establish a diagnosis.

For most drug-induced acneiform eruptions, lesions gradually resolve following discontinuation of the drug or a decrease in dosage, although steroid dependency can lead to prolonged and severe flares following withdrawal.^1,9 Topical agents, such as clindamycin and benzoyl peroxide, can also be used for management.¹⁰

The patient described in our case was almost finished with his current cycle of reinduction therapy, so he was advised to complete the course and then discontinue dexamethasone. On follow-up 1 week later, most of his lesions had resolved.

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Eman Bahrani, BA, is a medical student and Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston.

References

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2. Zitelli K, Fernandes N, Adams BB. Eosinophilic folliculitis occurring after stem cell transplant for acute lymphoblastic leukemia: a case report and review. Int J Dermatol. 2015;54(7):785-789.
3. Long H, Zhang G, Wang L, Lu Q. Eosinophilic skin diseases: a comprehensive review [published online April 16, 2015]. Clin Rev Allergy Immunol. doi: 10.1007/12016-015-8485-8.
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5. Sabater-Marco V, Escutia-Muñoz B, Botella-Estrada R. Eosinophilic follicular reaction induced by Demodex folliculorum mite: a different disease from eosinophilic folliculitis. Clin Exp Dermatol. 2015;40(4):413-415.
6. Basarab T, Russell Jones R. HIV-associated eosinophilic folliculitis: case report and review of the literature. Br J Dermatol. 1996;134(3):499-503.
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10. Dessinioti C, Antoniou C, Katsambras A. Acneiform eruptions. Clin Dermatol. 2014;32(1):24-34.
11. Lipozenčić J, Hadžavdić SL. Perioral dermatitis. Clin Dermatol. 2014;32(1):125-130.
12. Dey VK. Misuse of topical corticosteroids: a clinical study of adverse effects. Indian Dermatol Online J. 2014;5(4):436-440.
13. Shibata M, Katsuyama M, Onodera T, et al. Glucocorticoids enhance toll-like receptor 2 expression in human keratinocytes stimulated with Propionibacterium acnes or proinflammatory cytokines. J Invest Dermatol. 2009;129(2):375-382.
14. Nieschlag E, Vorona E. Mechanisms in endocrinology: medical consequences of doping with anabolic androgenic steroids (AAS): effects on reproductive functions. Eur J Endocrinol. 2015;173(2):R47-R58.