Are You Confident of the Diagnosis?
What you should be alert for in the history
Patients may or may not have a history of rosacea; it is controversial as to whether this is a variant of rosacea or a separate entity.
Characteristic findings on physical examination
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On physical exam, there is usually no persistent facial erythema and the eruption is not limited to convex surfaces; yellow, brown, red, or flesh-colored monomorphic firm papules or nodules occur on the face, often periorificial (around the eyes, nose, and mouth) (Figure 1). They can be on the lateral sides of the face and on the neck. Symmetry may be prominent. Extrafacial lesions on the ears, trunk, axillae, or extremities can be seen.
Expected results of diagnostic studies
Histopathology shows granulomatous inflammation; about 10% will show caseating necrosis. Histopathology may resemble sarcoidosis, lupus miliaris disseminatus faciei, or mycobacterial infection (Figure 2).
Figure 2.
Granulomatous rosacea histology (Courtesy of Bryan Anderson, MD).

Diagnosis confirmation
Diagnosis is confirmed by the clinical appearance and supportive histopathology. If tuberculosis is considered, tissue culture should be done; the patient should not have clinical evidence of sarcoidosis or tuberculosis. Demodex folliculitis typically presents with small follicular-based pustules. A scrapping of the pustule and microscopic examination will show multiple demodex mites.
Who is at Risk for Developing this Disease?
It is unclear whether there are particular risk factors for developing granulomatous rosacea. It appears to be more common in adult females.
What is the Cause of the Disease?
Etiology and pathogenesis is unknown. It has been suggested that demodex mites may trigger an antigenic response leading to granuloma formation. Ultraviolet radiation while inducing sun damage has been thought to lead to increased matrix metalloproteinase (MMP)-2 and MMP-9 which recruits inflammatory cells during the remodeling process and may lead to granuloma formation. The disease may be seen in association with H. pylori infections, however, this has not been substantiated. Also, there may be an association with granulomatous rosacea and Crohn’s disease. This may be due to NOD2/CARD15 gene mutations or polymorphisms. Further research is needed to determine if it is a true association.
Systemic Implications and Complications
Granulomatous rosacea is not definitively associated with any systemic disorders.
Evaluation of the patient with suspected granulomatous rosacea should include a skin biopsy, screening history, and review of symptoms for sarcoidosis and tuberculosis, and a purified protein derivative (PPD) or QuantiFERON®-TB Gold test. A tissue culture for mycobacteria may be done, if there is concern about a mycobacterial infection.
Treatment Options
Treatment is difficult as the disease often proves recalcitrant. There is little supporting data; treatment options are based on case reports, case series, and expert opinion.
Medical
Topical
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Azelaic acid
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Benzoyl peroxide
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Low potency topical corticosteroids
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Metronidazole
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Pimecrolimus 1% cream
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Sunscreen and sun protection
Systemic
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S ystemic tetracyclines (tetracycline 250 mg daily to 500 mg twice daily; minocycline 50-100 mg twice daily; doxycycline 50-100 mg twice daily)
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Erythromycin 500 mg two to four times daily
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Long-term, low-dose isotretinoin (5-10 mg/day) can be used for patients with more severe symptoms
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Systemic corticosteroids
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Dapsone
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Thalidomide
Surgical
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Mechanical dermabrasion, laser resurfacing, or shave removal of individual lesions may improve the appearance, but there is little evidential support for these methods.
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Photodynamic therapy with aminolevulinic acid
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Pulsed dye laser
Optimal Therapeutic Approach for this Disease
Therapy should begin with a trial of oral antibiotics for 2-4 months. If the patient fails to improve or worsens, long-term, low-dose isotretinoin should be considered.
Topicals are helpful for mild disease or as an adjuvant.
Surgical options should be considered only after medical options have failed, or when targeted at a single lesion or small treatment area.
Patient Management
The patient should be brought back for follow up in 2-4 months for follow-up if therapy is initiated. Isotretinoin use will require more frequent monitoring and blood work.
It is important to educate the patient that this disease can be recalcitrant to therapy.
Evaluation of the patient with suspected granulomatous rosacea should include a skin biopsy, screening history, review of symptoms for sarcoidosis and tuberculosis, and a purified protein derivative (PPD) test or QuantiFERON®-TB Gold test. Tissue culture for mycobacteria may be done, if there is concern about a mycobacterial infection.
Unusual Clinical Scenarios to Consider in Patient Management
Granulomatous rosacea is rarely diagnosed in childhood. It may be seen more frequently in immunosuppressed individuals.
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