Extrafacial and Generalized Granulomatous Periorificial Dermatitis

OBSERVATION Extrafacial and Generalized Granulomatous Periorificial Dermatitis

Amy J. Urbatsch, MD; Ilona Frieden, MD; Mary L. Williams, MD; Boni E. Elewski, MD; Anthony J. Mancini, MD; Amy S. Paller, MD

Background: Granulomatous periorificial dermatitis is limiting, and were not associated with systemic involve- a well-recognized entity presenting most commonly in ment. Resolution seemed to be hastened with the use of prepubertal children as yellow-brown papules limited to systemic antibiotic therapy in 4 of the 5 patients. the perioral, perinasal, and periocular regions. The condition is self-limiting and is not associated with sys- Conclusions: Extrafacial lesions can occur in granulo- temic involvement. matous periorificial dermatitis and do not appear to ad- versely affect the duration, response to therapy, or risk Observations: We reviewed the medical charts of 5 of extracutaneous manifestations. Overly aggressive evalu- healthy children presenting with extrafacial granuloma- ation and inappropriate systemic therapy should be tous papules in addition to the typical periorificial avoided. papules. These extrafacial lesions were clinically and histologically identical to the facial lesions, were self- Arch Dermatol. 2002;138:1354-1358

1 N 1970, Gianotti et al described REPORT OF CASES 5 children with monomorphic perioral papules that showed a CASE 1 granulomatous pattern when lesional biopsy sections were ex- A 23-month-old white boy with no history amined.I Since then, several additional pa- of skin disease developed lesions on his right tients have been reported and the condition leg at the injection site 2 weeks after vari- has been variably called Gianotti-type peri- cella vaccination. During the subsequent oral dermatitis, sarcoidlike granulomatous month, lesions became widely dissemi- dermatitis, facial Afro-Caribbean child- nated, but were asymptomatic and had never hood eruption (FACE), granulomatous peri- been associated with fever, weight loss, oral dermatitis, and, most recently, granu- cough, shortness of breath, or ocular com- lomatous periorificial dermatitis (GPD).2-9 plaints. He was otherwise healthy and there All affected patients have been healthy pre- was no family history of similar skin le- pubertal children, and the eruption was sions. The skin lesions were initially treated confined to the skin surrounding the with 0.1% triamcinolone acetonide oint- mouth, nose, and eyes in 56 of 59 pa- ment for 3 weeks without improvement. From the Department of tients described.1-14 The 3 patients with The findings from the physical ex- Dermatology, University of extrafacial involvement who were de- amination 4 months after the onset of the Alabama at Birmingham scribed in the literature had lesions on the rash showed an active boy with thou- (Drs Urbatsch and Elewski); neck, upper trunk, extensor wrists, and sands of discrete 1- to 3-mm red to yellow- Department of Pediatric vaginal area.14,15 brown papules on his scalp, face, trunk, Dermatology, University of We describe 5 prepubertal children and extremities (Figure 3). The highest California at San Francisco with periorificial granulomatous derma- concentration of lesions was around his (Drs Frieden and Williams); Figure 4 and Department of Pediatric titis, but with extensive extrafacial in- mouth, nose, and eyes ( ). The Dermatology, Northwestern volvement as well. The clinical character- rest of the physical examination findings University Medical School, istics of our 5 patients and the 3 cases from were normal. Chicago, Ill (Drs Mancini the literature are summarized in Table 1. The examination of 3 serial lesional and Paller). Two of the cases are outlined herein. biopsy specimens showed noncaseating

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©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Table 1. Demographic and Clinical Data of Patients With Extrafacial Periorificial Granulomatous Dermatitis

Patient No./ Extracutaneous Treatment Sex/Age, y Distribution Involvement Histologic Features Treatment Duration, mo* 1/M/2 Face, scalp, trunk, None Perifollicular granulomas Topical triamcinolone acetonide; 3wk;2mo extremities oral erythromycin estolate 2/F/12 Face, scalp, neck, ears Blepharitis Perifollicular granulomas Topical desonide; oral hydroxychloroquine 2wk;2mo;6wk sulfate, oral cyclosporine; oral minocycline, topical metronidazole 3/F/8 Face, upper trunk, Blepharitis, Perifollicular granulomatous Oral azithromycin, 1mo extremities lower tarsal infiltrate topical metronidazole papules 4/F/6 Face, labia majora None No data Oral and topical erythromycin 2 mo 5/F/8 Face, arms, abdomen, None Perifollicular granulomatous Oral erythromycin, Unknown labia majora† infiltrate topical metronidazole 6/M/415 Face, neck, upper trunk None Perifollicular granulomatous None 3 mo infiltrate 7/F/814 Face, ears, None Perifollicular granulomatous Oral macrolide antibiotic 6 mo extensor wrists infiltrate 8/F/814 Face, labia majora None Perifollicular granulomatous Oral macrolide antibiotic 6 mo infiltrate

*Time to resolution after treatment was started. †See Figure 1 and Figure 2.

Figure 1. Confluent erythematous scaly papules around the mouth and nose of patient 5.

granulomas in the dermis, many alongside the hair follicles (Figure 5). The results of special stains for acid- fast bacilli and fungus were negative, and cultures yielded no organisms. A polarization test for foreign material was negative. A chest x-ray film and findings of an ophthalmologic examination were normal and a purified pro- tein derivative test was nonreactive. Because of the resemblance of the patient’s condition to GPD, oral erythromycin estolate, 125 mg 3 times daily, was administered. This treatment resulted in dra- matic flattening of the lesions after 1 month of therapy and resolution of all lesions 6 months after the initiation of therapy and left mild atrophodermic scarring. The erythromycin regimen was tapered and discontinued af- Figure 2. Small dome-shaped papules and erythema on the labia majora of ter 9 months of treatment. Within 1 month after discon- patient 5. tinuation of the erythromycin, the lesions began to re- cur, once again initially at the site of the varicella vaccination. Treatment with oral erythromycin es- CASE 2 tolate, 125 mg 3 times daily, was restarted and again resulted in flattening of the lesions within 1 month. The A 12-year-old white girl with no significant medical his- resolved lesions left shallow pitted scars that resembled tory had a 1-year history of diffuse hair thinning. Two follicular atrophoderma (Figure 6). months later, she also developed hundreds of nonpru-

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©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Figure 3. Thousands of discrete reddish brown papules on the trunk and extremities of patient 1. The confluence of these lesions periorificially is striking.

Figure 5. Noncaseating perifollicular granulomas on histologic examination of a papule from the trunk of patient 1 (hematoxylin-eosin, original magnification ϫ100).

Figure 4. Diffuse reddish brown papules were most concentrated in the perioral region of patient 1.

ritic lesions on her face and neck. She denied fever, weight loss, cough, shortness of breath, or arthralgias. She had had recurrent episodes of blepharitis during the previ- ous year, but had never experienced any visual distur- bances. There was no family history of skin lesions, eye abnormalities, or hair loss. The results of a physical examination 14 months after the onset of hair loss showed diffuse thinning of her scalp hair that was most pronounced on the vertex of the Figure 6. Resolution of the lesions on the trunk of patient 1 after the scalp, with widening of the central part. Scarring was not initiation of therapy with erythromycin estolate. The shallow pitted scarring apparent. She had hundreds of discrete flesh-colored pap- resembles follicular atrophoderma. ules with varying amounts of surrounding erythema and scale, on her scalp, face, ears, and neck. The facial le- showed no abnormalities. A chest x-ray film, results of sions were predominantly located periorally. The re- pulmonary function tests, and an electrocardiogram were sults of the examination also disclosed erythema and scale also normal. along the margins of her eyelids and shotty posterior cer- The patient was initially treated with desonide lo- vical lymphadenopathy. tion for 2 weeks, with worsening of the skin lesions. A Four lesional skin biopsy specimens were obtained presumptive diagnosis of sarcoidosis was made and oral from the scalp and neck; all showed granulomas in the hydroxychloroquine sulfate, 200 mg daily, and oral cy- dermis, mostly around the hair follicles (Figure 7). Fo- closporine, 150 mg daily, were administered. Medica- cal epidermal spongiosis overlay some of the hair fol- tions were discontinued after 2 months of therapy when licles. The results of special stains and cultures were nega- no improvement occurred. Because of the resemblance tive for mycobacteria and fungus. to granulomatous perioral dermatitis, oral minocycline Laboratory evaluation, including a complete blood hydrochloride, 100 mg twice daily, and topical 0.75% met- cell count, chemistry panel, calcium level, erythrocyte ronidazole, administered twice daily, were initiated, lead- sedimentation rate, VDRL test, thyroid function tests, and ing to resolution of all skin lesions within 6 weeks with- serum levels of antinuclear antibody and testosterone, out scarring. The minocycline was tapered during a

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©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 4-month period. The patient continues to use the 0.75% The primary lesion is a discrete 1- to 3-mm dome- metronidazole lotion twice a day. Her scalp hair is still shaped papule that is red or yellow-brown. In some in- thin, but no further hair loss or new skin lesions have stances erythema surrounds the papule and overlying scale been noted 6 months after the discontinuation of the mi- is present. As in classic periorificial dermatitis, the face nocycline. is always involved, with lesions concentrated around the mouth, nose, and eyes. Some cases of GPD have de- COMMENT scribed prominent involvement of the helices of the ears as an important diagnostic feature.2,6 Granulomatous periorificial dermatitis is thought to be Scarring is variable. The initial cases described by a less common variant of perioral dermatitis. Perioral der- Gianotti et al1 and several subsequent authors2,13,14 re- matitis is an eruption characterized by grouped red pap- ported the occurrence of small pitted scars after resolu- ules, pustules, or papulovesicles and diffuse erythema and tion of the papules. This same type of scarring was seen scaling around the mouth, nose, and eyes that can be seen in one of our patients (patient 1) and is likely a result of in children.16 The lack of pustules and the presence of the inflammatory process. discrete yellow-brown papules, less prominent ery- Although the histologic appearance alone is not di- thema and scaling, and a perifollicular granulomatous in- agnostic, cases in which skin biopsy was performed have filtrate on examination of a biopsy specimen can differ- shown a dermal granulomatous infiltrate, usually con- entiate GPD from perioral dermatitis.9 Most reported cases centrated around the upper half of normal, nondis- of GPD have occurred in prepubertal children. The dis- rupted hair follicles. In some biopsy specimens, the in- ease affects both sexes almost equally. According to the filtrate has been more diffuse, with multiple epithelioid literature, GPD is seen more commonly in dark- macrophages, lymphocytes, and giant cells; in others, well- skinned patients, but this observation may reflect popu- formed noncaseating granulomas are surrounded by lym- lation bias and, in fact, all but 1 of our cases occurred in phocytes. Focal epidermal spongiosis is occasionally white patients. described. The results of special stains and cultures for acid-fast bacilli and fungi are always negative. The etiology of this condition is unknown. In some cases the eruption was linked to an external allergic or irritant contactant. The essential oils in bubble gum, an- tiseptic solution, formaldehyde, and black synthetic mesh are among the incriminated agents.2-4,12 Topical fluori- nated corticosteroids have been incriminated in trigger- ing and exacerbating GPD.5 In patient 1, the eruption was temporally and positionally related to varicella vaccination. Granulomatous periorificial dermatitis may repre- sent a nonspecific granulomatous response to a variety of topical or systemic agents. Granulomatous periorificial dermatitis is a benign and self-limited condition without any systemic manifestations. Occasionally, blepharitis or conjunctivitis is an associated finding, and blepharitis occurred in patients 2 and 3. Results of routine laboratory studies and ophthalmologic examination are usually normal; a chest radiograph is likewise usually normal. Spontaneous reso- Figure 7. Small, well-formed dermal perifollicular granulomas on histologic examination of a papule from the scalp of patient 2 (hematoxylin-eosin, lution usually occurs by a few months to 3 years after original magnification ϫ200). onset.1-15 The administration of oral macrolides or tetra-

Table 2. Differential Diagnosis of Granulomatous Papules in Children

Disorder Clinical Characteristics Extracutaneous Manifestations Histologic Features Sarcoidosis18 Red to yellow-brown papules on face; Constitutional symptoms, uveitis, Noncaseating epithelioid granulomas violaceous plaques on trunk; arthritis, lymphadenopathy, ichthyosis pulmonary involvement Infection (fungal, mycobacterial)19 Papules, nodules, pustules on face or Constitutional symptoms, Caseating granulomas, giant cells, body multiorgan involvement epithelioid macrophages, neutrophils Granulomatous rosacea17 Diffuse red or brown papules; Blepharitis, conjunctivitis Perifollicular granulomas, diffuse erythema, pustules, telangiectasias lymphohistiocytic infiltrate Familial juvenile systemic Translucent skin-colored papules on Uveitis, synovitis, arthritis Noncaseating epithelioid granulomas granulomatosis (Blau trunk and extremities syndrome)20 Granulomatous periorificial Small red to brown papules clustered Blepharitis Perifollicular noncaseating granulomas, dermatitis8 around mouth, nose, eyes, genital diffuse granulomatous infiltrate region

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©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 cyclines, alone or in combination with topical erythro- was expanded to periorificial because lesions could oc- mycin, metronidazole, or sulfur-based lotions, hastens cur around the nose and eyes, it may be necessary to fur- resolution in most patients. ther expand this entity to include extrafacial lesions as The differential diagnosis of small papules with well. granulomatous histologic features in children includes sarcoidosis, fungal or mycobacterial infection, familial ju- Accepted for publication February 21, 2002. venile systemic granulomatosis (Blau syndrome), and Corresponding author: Amy J. Urbatsch, MD, Depart- granulomatous rosacea (Table 2). In typical cases of ment of Dermatology, University of Alabama at Birming- GPD, these entities can be differentiated clinically. In cases ham, 70018th St S, Suite 414, Birmingham, AL 35233 with extrafacial involvement, other disorders can be dif- (e-mail: [email protected]). ferentiated by a thorough history and physical examination, a review of symptoms, examination of a chest ra- REFERENCES diograph, an ophthalmologic examination, and the use

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