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A Case of granulomatous rosacea: Sorting granulomatous rosacea from other granulomatous diseases that affect the face

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A case of granulomatous rosacea: Sorting granulomatous rosacea from other granulomatous diseases that affect the face.
Omar Khokhar MD, and Amor Khachemoune MD CWS
Dermatology Online Journal 10 (1): 6

Division of Dermatology, Georgetown University Medical Center, Washington, DC.


Granulomatous rosacea is a variant of rosacea that may present similar to other granulomatous diseases. We present the case of a 45-year-old woman with a 2-year history of facial erythema with multiple papules and pustules on the cheeks, chin, and glabella. The patient responded to minocycline, resulting in healing 6 months without residual scarring. This patient's clinical and histological presentation and treatment outcome are to our assessment consistent with granulomatous rosacea. However, other clinically and histologically related entities will be discussed. These entities include, but are not limited to, perioral dermatitis, granulomatous periorificial dermatitis, lupus miliaris disseminatus faciei, facial afro-caribbean eruption syndrome, and sarcoidosis.

Clinical summary

History.—An otherwise healthy 45-year-old woman presented with the progressive development of multiple papules and pustules on the cheeks, chin and glabella for 2 years. The patient denied the application of topical steroids on the face at any time. At the time of presentation, she was not taking any medications. Review of systems as well as the family history were unremarkable.

Figure 1 Figure 2
Facial erythema with glabellar involvement (fig. 1). Perioral papules (fig. 2)

Physical Examination.—Physical examination confirmed remarkable facial erythema and a papular eruption involving the cheeks, perioral area, and glabella (figs. 1 and 2). There were multiple small red to violaceous papules measuring 2-5 mm in diameter. Aside from the monomorphic papules, there were scattered pustules localized primarily to the perioral area. On diascopy, the papules appeared yellowish-brown. There was no involvement of the ears, neck, axillae, shoulders, groin, thighs, or knees. There was no lymphadenopathy. An ophthalmologic examination showed no evidence of keratitis, conjunctivitis, or blepharitis.

Laboratory Data.—A Purified Protein Derivative test was negative. A chest x-ray performed for a routine annual physical examination eleven months prior to her presentation was unremarkable.

Figure 3 Figure 3
Histology at scanning and higher magnification

Histology.—A biopsy of a papule of the cheek demonstrated dilated upper dermal capillaries associated with a lymphohistiocytic infiltrate predominantly centered on the hair follicles (figs. 3 and 4). Small noncaseating tuberculoid granulomata were noted. No Demodex mites were seen.

Diagnosis: Granulomatous rosacea


Rosacea typically presents with a wide spectrum of features, including congestion, flushing, telangiectasia, and rhinophyma [1]. The classification of rosacea has recently been standardized, and has led to the identification of four subtypes and one variant. The four subtypes are erythematotelangiectatic, papulopustular, phymatous, and ocular. Granulomatous rosacea is considered to be a part of the spectrum of rosacea, and is referred to as a variant of rosacea [2, 3]. We concur that granulomatous rosacea is a part of the spectrum of rosacea, and not a separate disease entity. Granulomatous rosacea has been reported primarily in middle-aged women, and in association with immunosuppression [4 ,5].

Clinically, granulomatous rosacea appears to be a distinctive papular form of rosacea that is found primarily on the butterfly and perioral areas. These discrete papules may appear as yellowish-brown hard nodules on diascopy, and may be accompanied by marked erythema. The size of the lesions may vary, and may be present at other areas of the body besides the above mentioned. Cases of granulomatous rosacea limited to the periocular skin have also been reported [6, 7].

Histological examination may reveal a spectrum of findings depending on the subtype of disease. These findings may range from a lymphohistiocytic response to a predominantly histiocytic response along with formation of noncaseating epithelioid-cell granulomas. These granulomas are of unknown etiology and may resemble those present in sarcoidosis [8]. A prominent characteristic of granulomatous rosacea is the presence of epithelioid histiocytes and multinucleate giant cells in tuberculoid granulomata, which may be centered on ruptured hair follicles. Nonpustular lesions show a nonspecific perivascular and perifollicular lymphohistiocytic infiltrate accompanied by occasional multinucleated cells, plasma cells, neutrophils, and eosinophils. Papulopustular lesions show more pronounced granulomatous inflammation and occasional perifollicular abscesses [9].

Rosacea has been linked with gastrointestinal disturbances, particularly those caused by Helicobacter pylori [10]. Recent studies have demonstrated the potential beneficial activity of clarithromycin, metronidazole, and pantoprazole on rosacea lesions [11-13].


     FACE      Facial Afro-Caribbean eruption syndrome    
     GR      Granulomatous Rosacea     
     GPD      Granulomatous Periorificial Dermatitis    
     LMDF      Lupus Miliaris Disseminatus Faciei    
     POD      Perioral Dermatitis    

There are several other conditions that present with similar clinical and histological features. Whether they are a part of the rosacea spectrum or completely different entities with rosacea-like features is controversial.

Perioral dermatitis (POD) is a chronic papulopustular facial dermatitis found in younger women and children. It appears to be a juvenile form of granulomatous rosacea [14]. The lesions are reported to resemble rosacea clinically and histologically [15]. POD manifests as grouped follicular reddish papules, papulovesicles and papulopustules on an erythematous base with a possible confluent aspect. Subjective symptoms consist of a sensation of burning, tension, and occasional itching. The etiology of POD is unclear; application of foundation, skin care ointments, and moisturizers, especially those with a petrolatum base and the vehicle isopropyl myristate, have been suggested as aggravating factors [16]. The correlation between potency of steroid and risk of developing POD is unknown. Drugs used to treat POD are primarily doxycycline, tetracycline, and minocycline. Oral isotretinoin may be considered in unresponsive and granulomatous forms [17].

Lupus miliaris disseminatus faciei (LMDF) is a rare caseating granulomatous condition that can present with inflammatory erythematous or flesh-colored papules distributed symmetrically across the eyelids, nose, and upper lip. The papules are usually multiple in number, smooth-surfaced, brownish-red, and 1-3 mm in size. Occasionally, the lesions may be generalized and appear on the extremities and/or trunk. Surrounding erythema is not a characteristic feature but may be present. Histological examination reveals a periappendigeal cellular infiltrate composed of lymphocytes and histiocytes with occasional neutrophils. Scattered lymphocytes, histiocytes and neutrophils may be present within the fibrotic areas [18]. This condition develops rapidly, is associated with scarring, and may be resistant to conventional treatment, thereby differentiating it from granulomatous rosacea. The etiology of LMDF is unclear. Some authors suggest that LMDF is a reaction to Demodex folliculorum, but the Demodex association has not been confirmed [19, 20, 21]. Studies have failed to demonstrate Mycobacterium tuberculosis or other mycobacterial diseases by culture [22, 23, 24]. We, along with others, believe that LMDF is a separate disease entity with granulomatous rosacea-like appearance, and not a more severe progression of rosacea [25].

Granulomatous periorificial dermatitis (GPD) is an eruption characterized by grouped papules, pustules, and diffuse erythema in prepubertal children. The primary lesion is a discrete 1-3 mm dome-shaped papule that is red or yellow-brown. The face is always involved, with lesions concentrated around the mouth, eyes, and nose. Scarring is variable [26]. Biopsies have shown a granulomatous infiltrate, usually concentrated around the upper half of normal nondisrupted hair follicles. The lack of pustules, presence of discrete yellow-brown papules, and a perifollicular granulomatous infiltrate on biopsy differentiate GPD from POD. Etiology is unknown. The administration of oral macrolides or tetracyclines, alone or in combination with topical erythromycin, metronidazole, or sulfur-based lotions, hastens resolution in most patients [27].

Facial afro-caribbean eruption (FACE) syndrome is a granulomatous dermatitis resembling POD. There is a profusion of monomorphic papules on the perioral, periocular, and perinasal areas. Black children are usually affected, and, because the histologic appearance is granulomatous, sarcoidosis is often considered [28]. Whether FACE is a variant of rosacea or separate disease is unclear [29].


Patients should be advised to avoid known exacerbating factors, such as hot drinks, alcohol, and extremes of temperature. They should be encouraged to use a noncomedogenic high-factor sunscreen when exposed to sunlight and wind [30]. Systemic tetracycline in doses ranging from 250 mg daily to 500 mg TID is usually very effective in treating acneiform lesions, with improvement evident within 2-4 months after commencement of therapy [31,32]. Alternatives include erythromycin 500 mg BID, minocycline 50-100 mg BID, or doxycycline 50-100 mg BID [33, 34]. In addition, topical metronidazole is helpful for mild disease and as an adjuvant to systemic therapy [35, 36, 37]. Topical keratolytics such as benzoyl peroxide and azelaic acid offer limited symptomatic control of inflammatory pustules [38, 39]. Isotretinoin may be helpful for recalcitrant disease, but recurrence is common. Long-term, low-dose isotretinoin therapy may be suitable for selected patients [34,35]. Dapsone has a pharmacological double function as both an antibiotic and an antiphlogistic drug [40]. The value of dapsone in granulomatous rosacea should be established by a controlled study. Permanent telangiectasia may be treated by electrosurgery or the 585 nm pulsed dye laser [41].

The patient in this case was treated with minocycline (100 mg BID) for 6 months. Treatment resulted in complete healing without residual scarring.


In summary, we believe this was a case of granulomatous rosacea that was controlled with minocycline without residual scarring. All the differential diagnoses mentioned in the discussion should be kept in mind with this clinical presentation. Histologic similarities of these conditions make it further difficult to differentiate granulomatous rosacea from other mimickers.


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