A Case of granulomatous rosacea: Sorting granulomatous rosacea from other granulomatous diseases that affect the face
Published Web Locationhttps://doi.org/10.5070/D39773c559
A case of granulomatous rosacea: Sorting granulomatous rosacea from other granulomatous diseases that affect the face.
Division of Dermatology, Georgetown University Medical Center, Washington, DC. firstname.lastname@example.org
Omar Khokhar MD, and Amor Khachemoune MD CWS
Dermatology Online Journal 10 (1): 6
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.
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 . 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 . 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 .
Rosacea has been linked with gastrointestinal disturbances, particularly those caused by Helicobacter pylori . Recent studies have demonstrated the potential beneficial activity of clarithromycin, metronidazole, and pantoprazole on rosacea lesions [11-13].
|FACE||Facial Afro-Caribbean eruption syndrome|
|GPD||Granulomatous Periorificial Dermatitis|
|LMDF||Lupus Miliaris Disseminatus Faciei|
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 . The lesions are reported to resemble rosacea clinically and histologically . 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 . 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 .
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 . 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 .
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 . 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 .
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 . Whether FACE is a variant of rosacea or separate disease is unclear .
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 . 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 . 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 .
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.
References1. Cohen AF, Tiemstra JD. Diagnosis and treatment of rosacea. J Am Board Fam Pract. 2002;15:214-7.
2. Helm KF, Menz J, Gibson LE, et al. A clinical and histopathologic study of granulomatous rosacea. J Am Acad Dermatol 1991;25:1038-43.
3. Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Am Acad Dermatol 2002;46:584-7.
4. Morras PG, Santos SP, Imedio IL, et al. Rosacea-like demodicidosis in an immunocompromised child. Pediatr Dermatol 2003;20:28-30.
5. Sanchez-Viera M, Hernanz JM, Sampelayo T, et al. Granulomatous rosacea in a child infected with the human immunodeficiency virus. J Am Acad Dermatol 1992;27:1010-1.
6. Smith KW. Perioral dermatitis with histopathologic features of granulomatous rosacea: successful treatment with isotretinoin. Cutis 1990;46:413-5.
7. Laude TA, Salvemini JN. Perioral dermatitis in children. Semin Cutan Med Surg 1999;18:206-9.
8. Simonart T, Lowy M, Rasquin F, et al. Overlap of sarcoidosis and rosacea. Dermatol 1997;194:416-8.
9. Helm KF, Menz J, Gibson LE, et al. A clinical and histopathologic study of granulomatous rosacea. J Am Acad Dermatol 1991;25:1038-43.
10. Rebora A, Drago F, Parodi A. May Helicobacter pylori be important for dermatologists? Dermatology 1995;191:6-8.
11. Millikan L. The proposed inflammatory pathophysiology of rosacea: implications for treatment. Skinmed 2003;2:43-7.
12. Mayr-Kanhauser S, Kranke B, Kaddu S, et al. Resolution of granulomatous rosacea after eradication of Helicobacter pylori with clarithromycin, metronidazole and pantoprazole. Eur J Gastroenterol Hepatol 2001;13:1379-83.
13. Herr H, You CH. Relationship between Helicobacter pylori and rosacea: it may be a myth. J Korean Med Sci 2000;15:551-4.
14. Laude TA, Salvemini JN. Perioral dermatitis in children. Semin Cutan Med Surg 1999;18:206-9.
15. Smith KW. Perioral dermatitis with histopathologic features of granulomatous rosacea: successful treatment with isotretinoin. Cutis 1990;46:413-5.
16. Malik R, Quirk CJ. Topical applications and perioral dermatitis. Australas J Dermatology 2000;41:34-8.
17. Kammler H (2002). http://www.emedicine.com/derm/topic321.htm. (Accessed January 6, 2004).
18. el Darouti M, Zaher H. Lupus miliaris disseminatus faciei--pathologic study of early, fully developed, and late lesions. Int J Dermatol 1993;32:508-11.
19. Ruffi T, Buchner SA. T-Cell subsets in acne rosacea lesions and the possible role of Demodex follicularum. Dermatologica 1984;169:1-5.
20. Amichai B, Grunwald MH, Avinoach I, et al. Granulomatous rosacea associated with Demodex folliculorum. Int J Dermatol 1992;31:718-9.
21. Erbagci Z, Ozgoztasi O. The significance of Demodex folliculorum density in rosacea. Int J Dermatol 1998;37:421-5.
22. Walchner M, Plewig G, Messer G. Lupus miliaris disseminatus faciei evoked during pregnancy in a patient with cutaneous lupus erythematosus. Int J Dermatol 1998:37;864-7.
23. Skowron F, Causeret AS, Pabion C, et al. F.I.GU.R.E.: facial idiopathic granulomas with regressive evolution. is 'lupus miliaris disseminatus faciei' still an acceptable diagnosis in the third millennium? Dermatology 2000;201:287-9.
24. Hodak E, Trattner A, Feuerman H, et al. Lupus miliaris disseminatus faciei--the DNA of Mycobacterium tuberculosis is not detectable in active lesions by polymerase chain reaction. Br J Dermatol 1997;137:614-9.
25. van de Scheur MR, van der Waal RI, Starink TM. Lupus miliaris disseminatus faciei: a distinctive rosacea-like syndrome and not a granulomatous form of rosacea. Dermatology 2003;206:120-3.
26. Andry P, Bodemer C, Teillac-Hamel D, et al. Granulomatous perioral dermatitis in childhood: eight cases [abstract]. Pediatr Dermatol 1995;12:76.
27. Urbatsch AJ, Frieden I, Williams ML, et al. Extrafacial and generalized granulomatous periorificial dermatitis. Arch Dermatol 2002;138:1354-8.
28. Knautz MA, Lesher JL Jr. Childhood granulomatous periorificial dermatitis. Pediatr Dermatol 1996;13:131-4.
29. Williams HC, Ashworth J, Pembroke A, et al. FACE: Facial Afro-Caribbean childhood eruption. Clin Exp Dermatol 1990;15:163-6.
30. Landow K. Unraveling the mystery of rosacea: keys to getting the red out. Postgrad Med Online 2002;6.
31. Dahl MV, Katz HI, Krueger GG, et al. Topical metronidazole maintains remissions of rosacea. Arch Dermatol 1999;134:679-83.
32. Veien NK, Stahl D, Brodthagen H. Granulomatous rosacea treated with tetracycline. Dermatologica 1981;163:267-9.
33. Bikowski JB. Treatment of rosacea with doxycycline monohydrate. Cutis 2000;66:149-52.
34. Caro I. Rosacea Briefs 2000;1;1-8.
35. Rebora A. The management of rosacea. Am J Clin Dermatol 2002;3:489-96.
36. Mayr-Kanhauser S, Kranke B, Kaddu S, et al. Resolution of granulomatous rosacea after eradication of Helicobacter pylori with clarithromycin, metronidazole and pantoprazole. Eur J Gastroenterol Hepatol 2001;13:1379-83.
37. Dahl MV, Jarratt M, Kaplan D, et al. Once-daily topical metronidazole cream formulations in the treatment of the papules and pustules of rosacea. J Am Acad Dermatol 2001;45:723-30.
38. Del Rosso JQ. Medical treatment of rosacea with emphasis on topical therapies. Expert Opin Pharmacother 2004;5:5-13.
39. Maddin S. A comparison of topical azelaic acid 20% cream and topical metronidazole 0.75% cream in the treatment of patients with papulopustular rosacea. J Am Acad Dermatol 1999;40:961-5.
40. Krause MH, Torricelli R, Kundig T, et al. Dapsone in granulomatous rosacea. Hautarzt 1997;48:246-8.
41. Taub AF. Treatment of rosacea with intense pulsed light. J Drugs Dermatol 2003;2:254-9.
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