Treatment-resistant granulomatous periorificial dermatitis in a 14-year-old female: Resolution after oral isotretinoin and methotrexate – A case report

Abstract

Childhood granulomatous periorificial dermatitis is an uncommon variant of periorificial dermatitis seen in patients under 18 years of age with several proposed triggers, including topical or inhaled corticosteroid exposure. We report and discuss a case of refractory childhood granulomatous periorificial dermatitis in a 14-year-old female with past inhaled corticosteroid use. After 7 months of isotretinoin therapy followed by 3 months of oral methotrexate, we observed complete resolution of her facial eruption.

Introduction

Periorificial dermatitis (PD) – or, traditionally, perioral dermatitis – is a common acneiform condition mainly affecting young women and children under 18 years of age. One variant of PD is childhood granulomatous PD (CGPD), a papulo-pustular periorificial dermatosis demonstrating granulomatous perifollicular infiltrates on histology. The etiology of CGPD is unclear, but several triggers are proposed, including topical or inhaled corticosteroids. Diagnosis of CGPD is often difficult because it demonstrates significant clinical and histological overlap with several other dermatoses. Misdiagnosis may lead to the initiation of inappropriate therapy, such as topical corticosteroids, thus undertreating and potentially exacerbating the condition.

Case report

A 14-year-old Caucasian female presented with a pruritic facial eruption beginning 2 months prior. Past medical history included suspected asthma (later ruled out) and chronic pain in the ribs and hands, followed by allergy and rheumatology, respectively. Medications included inhaled budesonide/formoterol 200/6 µg/inhalation (Symbicort) as needed and oral ibuprofen as needed. Allergies and family history were non-contributory. No significant changes occurred before the eruption besides the patient increasing the frequency of Symbicort to manage a recurrent cough experienced during sports.

Before presenting to the dermatology clinic, a walk-in clinic initially treated the eruption as allergic contact dermatitis (ACD), trialing a 5-day course of oral prednisone 30 mg once daily, topical hydrocortisone 1% cream twice daily, and discontinuing all products, with no improvement. Allergy subsequently continued topical hydrocortisone in various formulations and added oral cetirizine (Reactine) 10 mg once daily, with no improvement. Other failed treatments included topical terbinafine 1% (Lamisil) cream twice daily, topical tacrolimus 0.1% (Protopic) ointment once daily, topical betamethasone 0.1% (Betaderm) cream twice daily, and 2 weeks of oral doxycycline 100 mg twice daily. A comprehensive metabolic panel (CMP), complete blood count, lipid panel, and chest X-rays were unremarkable (Figure 1).

Figure 1.

Eruption at initial presentation demonstrates diffuse violaceous patches on the face with a few cysts.

At the initial dermatology visit, the eruption presented as violaceous patches in the periorbital, paranasal, and perioral regions, with edema and scaling around the nostrils and ears. The diagnosis was revised to perioral dermatitis secondary to inhaled corticosteroids based on prior Symbicort use. Treatment changes included decreasing the frequency of oral doxycycline 100 mg to once daily due to poor gastrointestinal tolerability, adding topical Fusidic acid 2% (Fucidin) ointment twice daily, and replacing Symbicort with inhaled salbutamol as needed.

At the 2-week follow-up, new papules on the cheeks suggested granulomatous pathology. Doxycycline was continued, with the addition of oral bilastine 20 mg (Blexten) once daily for pruritus, and topical ivermectin 1% (Rosiver) cream applied nightly.

An interim allergy workup for the recurrent coughing episodes resulted in a diagnosis of inducible laryngeal obstruction. Pending infectious disease serologies returned negative. Rheumatology considered juvenile dermatomyositis for fatigue and new subjective proximal muscle weakness, but an unremarkable workup led to a suspected diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, with investigation ongoing.

At the next dermatology follow-up, there was mild improvement of edema and color, but the medial cheeks now demonstrated numerous cysts. Treatment of the eruption consisted solely of Protopic once daily for 12 weeks, and doxycycline was completed 1 month prior. Protopic was discontinued, and oral isotretinoin 10 mg (Epuris) once daily was started, with Blexten continued to manage pruritus.

Nine weeks after initiating Epuris 10 mg once daily, partial resolution of edema and cysts was observed with worsening facial erythema and desquamation. A biopsy at this time was consistent with granulomatous perioral dermatitis (GPD). Epuris dose was doubled to 20 mg once daily (Figure 2).

Figure 2.

A skin biopsy with H&E stain demonstrates perivascular and perifollicular lymphoplasmacytic infiltrate in the superficial and mid dermis, along with early epithelioid noncaseating granulomas, and clusters of foreign-body type multinucleated giant cells under (a) 10× magnification and (b) 40× magnification.

After 5 months of Epuris 20 mg once daily, only erythema and desquamation persisted with new atrophic scarring on the forehead. Epuris was discontinued for 1 month to evaluate its role in the erythema and desquamation. A Protopic restart was not tolerated (Figure 3).

Figure 3.

After 3 months of methotrexate, erythema resolved completely, leaving only diffuse atrophic scarring.

One month later, the erythema partially resolved with persistent atrophic scarring. A repeat biopsy was consistent with partially resolved but persistent GPD. For completeness, a serum angiotensin-converting enzyme (ACE) level was completed and found normal. Oral methotrexate 15 mg once weekly was initiated. After 3 months, despite gastrointestinal tolerance issues, residual erythema resolved completely, leaving only atrophic scarring.

Discussion

In 1970, CGPD was initially diagnosed in five children and reported as “particuliére dermatite periorale infantile” by Gianotti et al. ¹ CGPD was briefly termed Facial Afro-Caribbean Childhood Eruption as subsequent cases were observed in Afro-Caribbean children. ² While CGPD is preferred by consensus today, ³ other terms include “Gianotti-type” perioral dermatitis, sarcoid-like granulomatous dermatitis, and childhood GPD.^2,4

Although the etiology of CGPD is uncertain, it affects children under 18 years of age.^3–6 Possible triggers mentioned in the literature include the occlusive effect of moisturizers and cosmetics, topical or inhaled corticosteroids, physical and hormonal triggers, among others.^2,4,7 CGPD presents as erythematous, periorificial papules and pustules, sparing a narrow zone around the lips.^2,3

Diagnosing CGPD remains challenging given its overlap with PD, granulomatous rosacea, and sarcoidosis, among others, resulting in a broad differential.^2,5 Often misdiagnosed as atopic dermatitis,^2,6,8 CGPD was initially misdiagnosed as ACD, then PD secondary to inhaled corticosteroid use in our case. Although CGPD is classified as a variant of PD, it is thought to exist on a spectrum between PD and childhood rosacea.^2,3,9 CGPD may be differentiated from PD by its involvement of additional facial regions, such as the periorbital area, as well as “extra-facial” regions, including the trunk, genitalia, or, in our case, the ears, whereas PD is generally confined to the perioral region.^2,3,5,7,10 The milia and atrophic scarring observed in our patient may occur during the resolution of CGPD. ¹⁰ Further complicating diagnosis, CGPD may histologically be mistaken for sarcoidosis on biopsy.^2,3 Although our patient experienced muscle weakness and fatigue, suggestive of sarcoidosis, ⁷ serum calcium, ACE level, and chest X-ray were unremarkable.

Some argue the self-limited course of CGPD negates treatment, but therapy aims to shorten lesion duration, as eruptions are benign but may persist for years, resulting in scarring.^4,8 No consensus exists for managing CGPD besides eliminating exacerbating exposures such as corticosteroids. ² Topical metronidazole, erythromycin, and pimecrolimus are first-line agents for patients under 8 years of age for whom systemic therapies are unsuitable. ⁴ One case report demonstrates complete resolution with oral metronidazole in a 9-year-old female with CGPD who failed topical metronidazole, citing it as an alternative when tetracyclines are contraindicated. ⁶ Tetracyclines may be considered in patients above 8 years of age or for lesions unresponsive to topicals. Topical and systemic treatments may also be used concurrently. Oral isotretinoin and methotrexate have both been suggested as successful treatment modalities for refractory CGPD.^4,11,12 We report partial resolution of CGPD with 7 months of oral isotretinoin therapy (Epuris 10 mg/day for 2 months, then 20 mg/day for 5 months) and subsequent complete resolution with 3 months of oral methotrexate (15 mg once weekly) after failing topical tacrolimus and oral doxycycline. Although spontaneous resolution due to the self-limited nature of CGPD cannot be excluded, oral isotretinoin and methotrexate may prove helpful to clinicians in treating refractory CGPD.