Cheilitis granulomatosa (Miescher granulomatous macrocheilitis) with trisomy 21Topiwala National Medical College and BYL Nair Hospital Mumbai, Maharashtra, India
Bhushan Sevakram Madke MBBS MD, Deepti Ghia MBBS, Reshma Gadkari MBBS, Chitra Nayak MBBS MD
Dermatology Online Journal 18 (6): 7
A 30-year-old male with Down syndrome presented to us with diffuse swelling of the lower lip of seven years duration. On examination, there was gross enlargement of his lower-lip with fissuring at places. A histopathological specimen from the lower lip showed non-caseating granulomas. We treated our patient with intralesional triamcinolone acetonide and oral clofazimine. We report this case because of the rare association of cheilitis granulomatosa with Down syndrome.
Miescher granulomatous macrocheilitis (cheilitis granulomatosa) is a mono-symptomatic form of Melkersson-Rosenthal Syndrome (triad of recurrent labial and/or recurrent facial edema, relapsing facial paralysis, and fissured tongue) . The complete classical presentation of Melkersson-Rosenthal syndrome is considered to be rare, occurring in only 25 to 40 percent of cases . The condition was first described by Miescher in 1945 . Orofacial granulomatosis is a unifying terminology showing similar clinical features and a broad spectrum of non-necrotizing granulomatous inflammation in the oral and facial region . Other entities that need to be considered in the differential diagnosis of orofacial granulomatosis include sarcoidosis, Crohn disease, and infectious disorders (e.g., tuberculosis). Until now, there is only a single case report of Melkersson-Rosenthal syndrome with Down syndrome .
|Figure 1||Figure 2|
|Figure 1. Diffuse enlargement of lower lip with fissuring in the midline. Note complete closure of both eyes ruling out facial
Figure 2. Simian crease on both the palms.
A 30-year-old male with Down syndrome was brought to our outpatient department with the chief complaint of gross swelling and deformity of the lower lip of seven years duration. Initially the swelling over the lower lip was episodic and recurrent in nature. However, for last three years, the swelling had tended to be persistent. Past history was significant for pleural effusion of tuberculous origin for which adequate treatment was completed. On detailed examination, our patient showed massive enlargement and protuberance of the lower lip with fissuring at the midline (median cheilitis) (Figure 1). The lips were firm and rubbery in consistency on palpation. No regional lymph gland enlargement was present. There was no other mucosal abnormality. His cutaneous examination showed a single palmar crease (simian crease), incurving of fifth finger (clinodactyly) (Figure 2), and increased gap between great and first toes (Figure 3). There was also a crease between the great and second toes of both feet (Kennedy crease) (Figure 3a).
|Figure 3||Figure 3a|
|Figure 3. Increased sandal gap between great and first toes.
Figure 3a. Note the Kennedy crease between the great and first toes.
Oral cavity and genital examination revealed no abnormality. Scalp examination showed greasy white flakes and mild erythema. There was no evidence of any facial nerve or other cranial nerve paralysis in our patient. We made a probable diagnosis of cheilitis granulomatosa with Down syndrome in our patient. His hemogram, serum biochemistry, and urinalysis were normal. Chest roentgenogram did not showed any abnormality. Mantoux test was negative in the patient. A 4 mm punch biopsy obtained from the lower lip showed foci of non-necrotizing granulomas composed of epitheloid cells interspersed with lymphocytes (Figures 4a and 4b).
|Figure 4a||Figure 4b|
|Figure 4a and 4b. H&E stained specimen showing foci of non-necrotizing granulomas in the mid dermis composed of epitheloid cells, plasma cells, and lymphocytes (x200).|
Stains for mycobacteria (Fite-Faraco) and fungi (PAS) were negative. The patient received intralesional triamcinolone acetonide 20 mg/ml at two-week interval along with oral clofazimine 100 mg three times a day.
Cheilitis granulomatosa is considered a form fruste of Melkersson-Rosenthal syndrome. Cheilitis granulomatosa has been reported in association with Crohn disease [6, 7, 8]. However, to be precise the exact association of cheilitis granulomatosa and Crohn disease remains unknown. Cheilitis granulomatosa is found in only 0.5 percent of patients with Crohn disease . Cheilitis granulomatosa usually presents with recurrent and episodic swelling of the upper lip (common), which subsides in a matter of a few hours. Hence it is commonly mistaken for angioedema without subjecting the patient to a thorough investigation. Gradually, the frequency of painless lip swelling increases and leads to a more persistent and firm swelling of both lips. Compression of lymphatics by the enlarging granulomas leads to an aggravation of swelling.
The differential diagnosis of acquired swelling of the lips is given in Table 1.
Patients with Down syndrome are burdened with an extra chromosome 21. The list of important phenotypic (Table 2) and mucocutaneous (Table 3) manifestations in an individual diagnosed with trisomy 21 is long and varied [10, 11].
Diagnosis of cheilitis granulomatosa relies on the typical history, clinical features and supportive evidence of non-caseating granulomas on histopathology. Two types of histology have been described for cheilitis granulomatosa (i) the sarcoid type with non-caseating granuloma consisting of epithelioid cells (histiocytes), lymphocytes, plasma cells, macrophages, and diffuse edema within the interstitial connective tissue and the (ii) lymphedematous type showing lymphatic distension, lymphedema, and plasma cell infiltration . However, one should bear in mind that granulomatous inflammation may not be evident in all biopsies of clinically involved lips and can only show edema, lymphangiectasia, and a sparse perivascular lymphoplasmacytic infiltrate. Our patient had the sarcoidal type of granulomatous inflammation present in the upper and mid dermis with edema, which corresponded to the massive swelling of his lower lip. However, no perilymphatic pathology was seen on pathology.
Treatment of cheilitis granulomatosa is a challenge for a physician. There are many drugs, which are reported to be useful in the management of cheilitis granulomatosa. Intralesional triamcinolone acetonide with lignocaine 2 percent is the first line of treatment for cheilitis granulomatosa . Intralesional triamcinolone acetonide (10-20 mg/ml) in the volume of 1.0-1.5 ml into each side of the lip leads to prompt resolution of inflammatory granulomas. Mental nerve blockade prior to corticosteroid injection will gain patient co-operation and one can inject a higher volume of corticosteroid. However, the response to intralesional steroid is of short duration and requires frequent painful injections. Other drugs that have been successfully used in cheilitis granulomatosa include dapsone, clofazimine , metronidazole , and roxithromycin . Because of a similar pathogenesis of cheilitis granulomatosa and Crohn disease, the TNF antagonist (infliximab) has been reported to be successful in the management of cheilitis granulomatosa . Owing to similar clinical and pathological features of cheilitis granulomatosa and sarcoidosis, hydroxychloroquine might prove useful in the treatment of cheilitis granulomatosa . Treatment resistant and disfiguring cases of cheilitis granulomatosa need surgical intervention in the form of surgical reduction and cheiloplastic procedures with adjuvant intralesional steroid injection to prevent relapse [22, 23].
To summarize, we have presented a rare case of cheilitis granulomatosa (Miescher granulomatous macrocheilitis) in a patient with Down syndrome.
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