Severe Granulomatous Rosacea in a Boy Successfully Treated with Topical Azelaic Acid

Dear Editor,

Rosacea is a common inflammatory dermatitis characterized by persistent erythema, telangiectasia, papules or pustules in the central convex area of the face. Its prevalence in children is low. Granulomatous rosacea (GR) is a distinct histological variant of it.[1] We describe here a case of childhood GR successfully treated with oral antibacterial agents followed by topical azelaic acid (AzA).

A 15-year-old Japanese boy presented with erythema on the forehead, lower eyelids, cheeks and perioral region with a symmetrical distribution for several months [Figure 1a]. There were no prior treatments, including topical corticosteroids. Histologically, the lesion on the forehead showed multiple non-caseating epithelioid cell granulomas with multinucleated giant cells in the dermis, accompanied by lymphocytes and histiocytes infiltrating into hair follicle epithelium [Figure 1b and c]. Grocott, Periodic acid-Schiff (PAS) and Ziehl-Neelsen stains revealed no infectious microorganisms. Laboratory studies, including the levels of angiotensin-converting enzyme and calcium, were all within normal limits. A chest X-ray, cardiac echogram and ophthalmological examination showed no evidence of sarcoidosis. We diagnosed this case as GR. Oral doxycycline at 200 mg and prednisolone at 5 mg a day were administered for 2 weeks, followed by roxithromycin at 300 mg. The lesions started to regress; however, erythema persisted, so topical DRX AZA (20% AzA cream) was subsequently started and roxithromycin was discontinued. The cutaneous lesions had almost completely resolved without scarring after 6months [Figure 1d]. The continuous use of topical AzA for a further year prevented any flaring up of the GR.

Figure 1.

(a) At first visit, a 15-year-old Japanese boy presented with erythema on the forehead, lower eyelids, cheeks and perioral region with a symmetrical distribution. (b) Histological findings of the lesion on the forehead showed multiple non-caseating epithelioid cell granulomas in the dermis with lymphocytes and histiocytes infiltrating into hair follicle epithelium (HandE stain, ×100). (c) Multinucleated giant cells were seen in the dermis (HandE stain, ×400). (d) Six months after the first visit, the erythema on the face had almost completely resolved

The histological features of GR are non-caseating epithelioid cell granulomas with or without follicular involvement, although the clinical manifestations vary (1). The differential diagnoses of childhood cases are granulomatous perioral dermatitis (GPD) and sarcoidosis. GPD is a rare self-limited dermatitis classically found in children of Afro-Caribbean descent.[2] As the histology of GPD can be identical to that seen in GR, some researchers have considered GPD and GR to be variants of the same disease in different ages and ethnic groups.[3]

The specific factors that cause the development of GR remain unclear. In some cases, Demodex folliculorum was detected within the central dilated follicular infundibula or in the center of the granuloma;[1] however, in the present case, it was not found. Besides external factors, recent molecular studies[4] have suggested that GR is associated with altered innate immune responses: Excess cathelicidin peptides in the epidermis and increased serine protease kallikrein 5 activity in the granular and cornified layers may play certain roles in the pathophysiology of rosacea.

A variety of therapeutic approaches are applied for childhood rosacea. Although topical AzA is a standard therapy for mild to medium papulopustular rosacea, to the best of our knowledge, its effectiveness for GR is not fully understood. Besides conventional pharmacologic mechanisms of AzA, including inhibition of microbial survival, modulation of epidermal differentiation and inhibition of reactive oxygen species,[5] recent research[4] has revealed that it can reduce cathelicidin and kallikrein 5 messenger RNA, which prevents inflammatory responses in the skin.

The present case suggests that topical AzA is useful for preventing relapse as well as treating GR in childhood.