1Department of Dermatology, Bahla Hospital, Bahla, Oman; 2Dermatology Program, Oman Medical Specialty Board, Muscat, Oman; 3Department of Pathology, Khoula Hospital, Muscat, Oman; 4Department of Dermatology, Al Nahdha Hospital, Muscat, Oman *Corresponding Author’s e-mail: mhhh1414@gmail.com التهاب اجللد الورمي احلبييب حول الفم يف شخص بالغ تقرير حالة مع مراجعة املعت�صم الق�صابي، خالد البو�صعيدي، كوثر البكو�س، عبلة الإ�صماعيلية abstract: Granulomatous periorificial dermatitis (GPD) is a benign, self-limiting eruption that is considered a clinical variant of periorificial dermatitis, also known as perioral dermatitis. It presents primarily in prepubertal children as monomorphic scaly papules over perioral, paranasal and periorbital areas of the face with rare occurrence in adults. We report a 36-year-old Omani male patient who presented to the Dermatology Clinic at Bahla Polyclinic, Bahla, Oman, in 2018 with a papular eruption over his face for the previous six months. Based on clinical and histopathological findings the patient was diagnosed with GPD with sarcoid-like histology. He was treated effectively with oral doxycycline and topical metronidazole. This report provides a review of the literature on GPD and summarises all reported cases in adults to date. Keywords: Perioral Dermatitis; Dermatitis; Granulomas; Case Report; Oman. امللخ�ص: التهاب اجللد الورمي احلبيبي حول الفوهة هو مر�س حميد ي�صفى تلقائيا ويعترب اأحد الأ�صكال ال�رشيرية لداء التهاب اجللد حول الفوهة والذي يعرف اأي�صا بالتهاب اجللد حول الفم. ي�صيب غالبا الأطفال ما قبل �صن البلوغ ويظهر على �صكل حبوب مت�صابهة عليها طبقة من الق�صور يف مناطق حول الفم والأنف والعني بالوجه مع ندرة حدوثه يف البالغني. نعر�س هنا حالة لذكر عماين عمره 36 �صنة قدم اإىل عيادة اجللد مبجمع بهالء ال�صحي، عمان، يف عام 2018 وهو يعاين من ثوران حطاطي يف الوجه منذ �صتة اأ�صهر. بناء على النتائج ال�رشيرية و فح�س الهي�صتوباثولوجيا مت ت�صخي�صه مبر�س التهاب اجللد الورمي احلبيبي حول الفوهة مع تغريات �صبيهه بال�صاركويد ن�صيجيًا. مت عالج املري�س بنجاح باإ�صتخدام عقار الدوك�صي �صيكلني عن طريق الفم ومرهم ميرتونيدازول. يقدم هذا التقرير مراجعة لالأدبيات املتعلقة بالتهاب اجللد الورمي احلبيبي حول الفوهة ويلخ�س جميع احلالت املبلغ عنها يف البالغني حتى الآن. الكلمات املفتاحية: التهاب اجللد حول الفم؛ التهاب اجللد؛ اأورام حبيبية روماتزمية؛ تقرير حالة؛ عمان. Granulomatous Periorificial Dermatitis in an Adult A case report with review of literature *Al-Mutasim Al-Qassabi,1 Khalid Al-Busaidi,2 Kaouthar Al Baccouche,3 Abla Al Ismaili4 Sultan Qaboos University Med J, February 2020, Vol. 20, Iss. 1, pp. e100–103, Epub. 9 Mar 20 Submitted 7 Aug 19 Revisions Req. 25 Sep & 14 Oct 19; Revisions Recd. 29 Sep & 16 Oct 19 Accepted 31 Oct 19 Case report A 36-year-old Omani male patient presented to the Dermatology Clinic at Bahla Polyclinic, Bahla, Oman, in 2018 with a papular eruption over his face for the previous six months. He reported no itching, burning sensation or facial redness. He had no known comorbidities and denied a history of fever, shortness of breath or other systemic complaints. In addition, he denied having used any topical or oral medications prior to the eruption. There was no recent history of travel and no abnormal environmental exposure. He was prescribed topical mometasone cream for two months and tacrolimus (0.1%) ointment for three months with partial response and recurrence once the treatment was discontinued. Following the reoccurrence of the papular eruption, examination showed monomorphic scaly erythematous papules localised to the perioral, paranasal and peri- orbital areas of the face [Figure 1]. The vermilion border Granulomatous periorificial dermatitis (GPD), also known as childhood granulo- matous periorificial dermatitis (CGPD), is an uncommon, benign inflammatory skin disease that affects primarily dark-skinned prepubertal children; few cases have been reported in adults.1–5 It is characterised by a monomorphic, skin-coloured to yellow-brown or red papular eruption around the mouth, nose and eyes that usually heals with no scarring. However, extra-facial lesions have been reported.6 GPD shares many similarities with granulomatous rosacea (GR) and cutaneous sarcoidosis. Some authors consider it a variant of GR, while others suggest that it may be a variant of sarcoidosis.7,8 This case report describes a rare case of GPD in an adult with sarcoid- like histology that was successfully treated with oral doxycycline and topical metronidazole. In addition, this report discusses controversies and distinguishing features of GPD from GR and sarcoidosis as well as a review of literature of all reported cases of GPD in adults. This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License. https://doi.org/10.18295/squmj.2020.20.01.015 case report https://creativecommons.org/licenses/by-nd/4.0/ Al-Mutasim Al-Qassabi, Khalid Al-Busaidi, Kaouthar Al Baccouche and Abla Al Ismaili Case Report | e101 was involved. There was no facial erythema or telan- giectasia. There were no other skin lesions and other orifices were not involved. The rest of the physical examination was unremarkable. The differential diagnoses included periorificial dermatitis, GR, cutaneous sarcoi- dosis and lupus miliaris disseminatus faciei (LMDF). Laboratory investigations, including angiotensin converting enzyme (ACE) levels, were normal. The chest X-ray was also normal. A punch biopsy was taken from the area with erythematous papules and sent for histo- logical investigation. Histopathological examination of an erythem- atous papule showed non-caseating naked granulomas containing histiocytes, multinucleated giant cell of Langhans type and focally surrounded lymphocytes [Figure 2]. Periadnexal and perivascular lymphocytic infiltrate was also present. Stains for fungi (i.e. periodic acid–Schiff ) and acid-fast bacilli (i.e. Ziehl-Neelsen and Wade-Fite) were negative. As a result of the clinical and histopathological findings, the patient was diagnosed with GPD. The patient was treated with oral doxycycline (100 mg) once daily and topical metronidazole cream twice daily. He showed marked improvement after six weeks with complete resolution of the lesions without scarring after 12 weeks, after which treatments were stopped [Figure 3]. He had no recurrence on follow-up visits after three and six months. The patient gave consent for his images and clinical information to be reported in a journal. The authors explained that while the patient’s name would not be published, complete anonymity could not be guaranteed. Discussion GPD is a well-recognised entity that affects commonly dark-skinned prepubertal children. While topical steroids are considered to be the most important and frequently reported pathogenic factor, other reported factors include cosmetic products, physical factors and microorganisms.1,8–11 GPD is a controversial disease as it shares many similarities with other granulomatous disorders such as GR and cutaneous sarcoidosis. GDP is distinguished from cutaneous sarcoidosis by the absence of systemic involvement and a self-limiting nature. Antony et al. reported a case of GPD that could be a variant of sarcoidosis with raised ACE levels and a chronic nature.8 GR usually shows similar histology to GPD but it mainly affects the central face and may show classic signs of telangiectasia, oedema and erythema.7 LMDF is distinguishable from GPD as it has a tendency to affect periorbital areas only, a presence of caseation on histology and resolution with scarring. Misago et al. reported a case of CGPD with similar features to LMDF suggesting that the term ‘facial idiopathic granulomas with regressive evolution’ should include both CGPD and LMDF.12 Since GPD sometimes presents with eczematous features, seborrheic dermatitis is also an accepted differential diagnosis, but the latter usually involves other areas such as the eyebrows and scalp with a dramatic response to topical steroids and different histologic features without granulomas. Dermatoscopy may show additional features that aid in diagnosis.13 Table 1 summarises the differential diagnoses with Figure 1: Photographs of the face of a 36-year-old male showing monomorphic erythematous scaly papules localised to (A) periorbital, (B) paranasal and perioral areas with involvement of vermilion border. Figure 3: Photographs of the face of a 36-year-old male showing complete resolution after 12 weeks of treatment with oral doxycycline and metronidazole cream. Figure 2: Haematoxylin and eosin stains at (A) x10 mag- nification showing non-caseating granulomatous inflamm- ation with some naked granulomas and (B) at x40 mag- nification showing surrounding lymphocytic infiltrate. Granulomatous Periorificial Dermatitis in an Adult A case report with review of literature e102 | SQU Medical Journal, February 2020, Volume 20, Issue 1 clinical and dermoscopic features of granulomatous papules on the face. GPD has a self-limiting nature, therefore treatment is not necessary. However, many topical and systemic treatments have been reported to hasten clearance.1,2,6,7,11,18 Topical treatments include metronidazole, erythromycin or pimecrolimus.1,6,11 Systemic treatments mainly include tetracycline antibiotics such as tetracycline and doxy- cycline; oral erythromycin and clarithromycin are also effective.2,7,18 To date, there are a total of six reported cases of GPD in adults [Table 2].1–5 The present case is the only case in a male. In two cases, the lesions were erythematous plaques and the remainder had erythematous papules as in the present case. All cases showed dermal non- caseating granulomas upon histopathological exam- ination. One case was treated with oral isotretinoin while the others were treated with oral antibiotics. All cases showed complete resolution without recurrence. Table 1: Differential diagnosis of granulomatous papules on the face11,13–17 Disease Typical patient characteristics Clinical features Main dermoscopic features Histopathological findings Prognosis GPD • Prepubertal children • Rarely seen in adults • Monomorphic, skin-coloured to yellow- brown or red papules confined to the periorificial areas of the face • Not described • Dermal non- caseating granulomas • Spontaneous resolution without scarring GR • Middle-aged women • Yellow-brown or pink papules on the cheeks, periorbital or perioral skin • Blushing, erythema or telangiectasia, may be seen • Linear reddish or purple vessels arranged in a polygonal network (vascular polygons) • Epithelioid granulomas adjacent to hair follicles • Caseation in 10% of the cases • Chronic nature Cutaneous sarcoidosis • Any age and gender • Non-inflammatory facial papules and nodules with systemic symptoms such as fatigue, weight loss, joint pain and pulmonary symptoms • Structure-less, orangish areas and well-focused linear or branching vessels • Naked, non-caseating granulomatous infiltration • Chronic nature LMDF • Young adults • Reddish-yellow or yellowish-brown papules on the central face and eyelids • Follicular keratotic plugs and vascular structures • Caseating granulomas • Spontaneous resolution with scarring GPD = granulomatous periorificial dermatitis; GR = granulomatous rosacea; LMDF = lupus miliaris disseminatus faciei. Table 2: Summary of reported cases of granulomatous periorificial dermatitis in adults1–5 Author and year of publication Age in years Gender Clinical presentation Histopathological findings Treatment (duration) Chintagunta et al.1 (2018) 34 Female Well-defined erythematous to pigmented plaques associated with scaling involving the perioral, paranasal and glabella Granulomatous inflammation in the dermis composed of lymphocytes, histiocytes, epitheliod cells and multinucleated giant cells Oral doxycycline 100 mg OD + pimecrolimus 1% cream BID (3 months) Vincenzi et al.2 (2000) 19 Female Numerous, flesh-coloured micropapular lesions involving the perioral and peri- nasal areas associated with a mild diffuse erythema and slight vesiculation Numerous well-formed granulomas containing occasional multinucl- eated giant cells in the dermis Oral clarithromycin 250 mg OD (6 weeks) then 125 mg OD (8 weeks) Vincenzi et al.2 (2000) 25 Female Numerous red micropapules involving the nasal folds and the perioral regions Perifollicular non-caseating epithe- lioid cell granulomas in the dermis with some multinucleated giant cells and a variable number of lymph- ocytes and histiocytes in perivas- cular and perifollicular areas Oral clarithromycin 250 mg OD (10 days) then 250 mg on alternate days (20 days) Tambe et al.3 (2018) 30 Female Multiple erythematous, scaly papules and plaques on the supra orbital, peri- orbital, perioral and perinasal area Perifollicular and perivascular granu- lomatous inflammatory infiltrate composed of lymphocytes, epithe- lioid cells and giant cells Oral isotretinoin 20 mg OD + metronidazole cream (3 weeks) Li et al.4 (2006) 28 Female Pink to normal skin-coloured, discrete and coalescing papules ranging from 1–3 mm in diameter over the face, nape and bilateral forearms Dermal granuloma formation around hair follicles, composed of lympho- cytes, epithelioid histiocytes and occasional multinucleated giant cells Oral doxycycline 100 mg OD + topical metronidazole gel (2 months) Loai and Huang5 (2015) 24 Female Multiple, discrete, red to brown papules on erythematous base on the perioral and periocular areas Granulomatous infiltration composed of lymphocytes, histiocytes, epithe- lioid cells and multinucleated giant cells, without caseation in the dermis Oral minocycline 50 mg bid + tacrolimus ointment 0.03% BID (50 days) Present case 36 Male Monomorphic scaly erythematous papules localised to the perioral, paranasal and periorbital areas of the face Non-caseating naked granulomas containing histiocytes, multinucl- eated giant cell of Langhans type and focally surrounded lymphocytes Oral doxycycline 100 mg OD + metronidazole cream (3 months) OD = once daily; BID = twice daily. Al-Mutasim Al-Qassabi, Khalid Al-Busaidi, Kaouthar Al Baccouche and Abla Al Ismaili Case Report | e103 Conclusion GPD is a well-recognised entity that may affect adults and should be differentiated from GR, cutaneous sarcoidosis and other granulomatous disorders of the face by clinicopathological correlation to minimise systemic treatment use. References 1. Chintagunta S, Manchala S, Arakkal G. Granulomatous peri- orificial dermatitis in an adult: A rare case report. J Dr NTR Univ Health Sci 2018; 7:143–6. https://doi.org/10.4103/2277- 8632.233845. 2. Vincenzi C, Parente G, Tosti A. Perioral granulomatous dermatitis: Two cases treated with clarithromycin. J Dermatolog Treat 2000; 11:57–61. https://doi.org/10.1080/09546630050517702. 3. Tambe S, Jerajani H, Pund P. Granulomatous periorificial dermatitis effectively managed with oral isotretinoin. Indian Dermatol Online J 2018; 9:68–70. https://doi.org/10.4103/idoj. IDOJ_129_17. 4. Li YW, Chuan MT, Hu SL. Granulomatous periorificial dermatitis in a young woman. Dermatol Sinica 2006; 24:38–41. https://doi.org/10.29784/DS.200603.0006. 5. Loai S, Huang C. Childhood granulomatous perioral dermatitis with good responses to minocycline and topical tacrolimus, extraordinary significance. Austin J Dermatol 2015; 2:1034. 6. Urbatsch AJ, Frieden I, Williams ML, Elewski BE, Mancini AJ, Paller AS. Extrafacial and generalized granulomatous periorificial dermatitis. Arch Dermatol 2002; 138:1354–8. https://doi.org/10.1 001/archderm.138.10.1354. 7. Lucas CR, Korman NJ, Gilliam AC. Granulomatous periorif- icial dermatitis: A variant of granulomatous rosacea in children? J Cutan Med Surg 2009; 13:115–18. https://doi.org/10.2310/77 50.2008.07088. 8. Antony FC, Buckley DA, Russell-Jones R. Childhood granulo- matous periorificial dermatitis in an Asian girl--A variant of sarcoid? Clin Exp Dermatol 2002; 27:275–6. https://doi.org/10.1 046/j.1365-2230.2002.01019.x. 9. Zalaudek I, Di Stefani A, Ferrara G, Argenziano G. Childhood granulomatous periorificial dermatitis: A controversial disease. J Dtsch Dermatol Ges 2005; 3:252–5. https://doi.org/10.1111/ j.1610-0387.2005.05009.x. 10. Hatanaka M, Kanekura T. Case of childhood granuloma- tous periorificial dermatitis. J Dermatol 2018; 45:e256–7. https://doi.org/10.1111/1346-8138.14296. 11. Lee GL, Zirwas MJ. Granulomatous rosacea and periorificial dermatitis: Controversies and review of management and treat- ment. Dermatol Clin 2015; 33:447–55. https://doi.org/10.1016/j. det.2015.03.009. 12. Misago N, Nakafusa J, Narisawa Y. Childhood granulomatous periorificial dermatitis: Lupus miliaris disseminatus faciei in children? J Eur Acad Dermatol Venereol 2005; 19:470–3. https://doi.org/10.1111/j.1468-3083.2004.01178.x. 13. Errichetti E, Stinco G. Dermatoscopy of granulomatous disorders. Dermatol Clin 2018; 36:369–75. https://doi.org/10.1016/j.det.2 018.05.004. 14. Khokhar O, Khachemoune A. A case of granulomatous rosacea: Sorting granulomatous rosacea from other granulomatous diseases that affect the face. Dermatol Online J 2004; 10:6. 15. Elder D, Elenitsas R, Johnson BL, Murphy GF. Lever's Histopathology of the Skin. 9th ed. Philadelphia, Pennsylvania, USA: Lippincott Williams and Wilkins, 2005. P. 469. 16. Ayhan E, Alabalik U, Avci Y. Dermoscopic evaluation of two patients with lupus miliaris disseminatus faciei. Clin Exp Dermatol 2014; 39:500–2. https://doi.org/10.1111/ced.12331. 17. Toda-Brito H, Aranha JMP, Tavares ES. Lupus miliaris dissemin- atus faciei. An Bras Dermatol 2017; 92:851–3. https://doi.org/10.1 590/abd1806-4841.20174534. 18. Choi YL, Lee KJ, Cho HJ, Kim WS, Lee JH, Yang JM, et al. Case of childhood granulomatous periorificial dermatitis in a Korean boy treated by oral erythromycin. J Dermatol 2006; 33:806–8. https://doi.org/10.1111/j.1346-8138.2006.00183.x. https://doi.org/10.4103/2277-8632.233845 https://doi.org/10.4103/2277-8632.233845 https://doi.org/10.1080/09546630050517702 https://doi.org/10.4103/idoj.IDOJ_129_17 https://doi.org/10.4103/idoj.IDOJ_129_17 https://doi.org/10.29784/DS.200603.0006 https://doi.org/10.1001/archderm.138.10.1354 https://doi.org/10.1001/archderm.138.10.1354 https://doi.org/10.2310/7750.2008.07088 https://doi.org/10.2310/7750.2008.07088 https://doi.org/10.1046/j.1365-2230.2002.01019.x https://doi.org/10.1046/j.1365-2230.2002.01019.x https://doi.org/10.1111/j.1610-0387.2005.05009.x https://doi.org/10.1111/j.1610-0387.2005.05009.x https://doi.org/10.1111/1346-8138.14296 https://doi.org/10.1016/j.det.2015.03.009 https://doi.org/10.1016/j.det.2015.03.009 https://doi.org/10.1111/j.1468-3083.2004.01178.x https://doi.org/10.1016/j.det.2018.05.004 https://doi.org/10.1016/j.det.2018.05.004 https://doi.org/10.1111/ced.12331 https://doi.org/10.1590/abd1806-4841.20174534 https://doi.org/10.1590/abd1806-4841.20174534 https://doi.org/10.1111/j.1346-8138.2006.00183.x