Melkersson-Rosenthal syndrome in a patient with tubercular panuveitis

We report a rare presentation of Melkersson-Rosenthal syndrome in presented unilateral, right upper eyelid Excision biopsy showed granulomatous in ﬂ ammation involving the lymphatics. Immunohistochemistry con ﬁ rmed the presence of histiocytes around the lymphatics.

causing retinal edema. This further leads to exudative retinal detachment. The consequence of this entire process is retinal hypoxia and further neovascularization. [6] Sun et al. showed elevated levels of VEGF in Coats' disease which rapidly reduced aft er injection of pegaptanib sodium. VEGF levels reduced from 908 pg/ml to 167 pg/ml (normal -100 pg/ml) and an improvement of exudation, hemorrhage and near complete reatt achment of the retina . Thus, they suggested that there may be a component of dysregulation of VEGF-mediated angiogenesis in Coats' disease. [4] In our case series, we had not obtained consent for biochemical analysis except in Case 3 where we confi rmed our diagnosis with light microscopy and histopathology of the drainage fl uid.
More recently, Venkatesh et al. reported two older children (14 years and 16 years) with Coats' disease treated with intravitreal bevacizumab (1.25 mg/0.05 ml). They concluded that despite reduction of macular edema, exudation and telangiectasia aft er injection, intravitreal injection may not alone suffi ce in all cases. [5] In none of the cases reported so far, there has been any consideration for titrating the dose of anti-VEGF agents considering the smaller volume of eye in children. [4,5] Anti-VEGF being an adjunct treatment, the timing of this may be varied depending on the clinical judgment. In cases with extensive exudation and media haze, laser may be deferred while anti-VEGF agents may be the preferred treatment. Due to their anti-permeability role, they may be utilized to clear the exudation and media haze to visualize the vessels for ablation. Also, in cases such as Case 1, with previous unsuccessful laser treatment for macular edema, anti-VEGF agents may be the preferred treatment.
Our communication highlights the merit of augmenting intravitreal injection with conventional treatment (laser/cryo/ needle drainage). With increasing use of anti-VEGF agents in younger age patients for diseases such as retinopathy of prematurity (ROP) and Coats' disease, clinicians should also bear in mind the role of VEGF in the development of retinal vessels not only in the retinal periphery, but also in the macula. Long-term visual outcomes of the use of anti-VEGF agents in children are unknown. Until such time cautious use of anti-VEGF agents is advisable. Repeated injections of anti-VEGF agents are required to control the neovascular response in age-related macular degeneration (AMD). In Coats' disease, it is possible that with anti-VEGF therapy, repeated injections may be needed. However, with the use of concomitant therapeutic modalities such as laser, cryo and needle drainage, we can minimize the need for repeated injections.
Due to the multiple procedures done before injection of anti-VEGF agents in our cases, it is diffi cult to determine if anti-VEGF agents alone were responsible for the anatomical success that was seen especially in Cases 2 and 3. We did not encounter any systemic or ocular side-eff ects (e.g.: increased intraocular pressure) in these three patients. A larger study would be needed to affi rm the safety and effi cacy of intravitreal injections in the pediatric population.
involvement is more common. [1,2] Histopathology showing the presence of perilymphatic granuloma, lymphangiectasia and granulomatous lymphangitis is diagnostic of the above syndrome. [3] Occasional reports of isolated painless, nonpitt ing and unilateral eyelid edema due to MRS has been described. [1,2,4] We report a case of isolated eyelid edema due to MRS, confirmed histopathologically, in a patient with tubercular panuveitis.

Case Report
A 45-year-old male was being treated for tubercular panuveitis in both eyes since one year with four-drug regimen of antitubercular therapy (ATT) which included isoniazid, rifampicin, pyrazinamide, ethambutol for two months followed by isoniazid, rifampicin and pyrazinamide for ten months. ATT was given for a possible tubercular etiology on the basis of a strongly positive Mantoux test (25-mm induration), a calcifi ed nodule on chest X-ray and demonstration of Mycobacterium tuberculosis (MTb) genome by polymerase chain reaction (PCR) on the vitreous sample. He had no recurrences and there was complete resolution of ocular infl ammation following treatment with ATT. During his follow-up visits, he gave a history of intermitt ent right upper eyelid swelling since the last four months, which was more prominent during the day. Past history revealed a history of recurrent left -sided facial edema five years previously for which no investigations were done at that point of time. He did not have any facial nerve palsy or furrowed tongue at presentation. On ocular examination, a firm, non-tender and non-pitting edema involving the entire right upper eyelid was seen. [Fig. 1] His best corrected visual acuity was 20/20 in both eyes. Slit-lamp examination was unremarkable. Fundus examination showed areas of healed retinal vasculitis and multifocal choroiditis. Thyroid function tests, renal function tests and computed tomography of the cranium and orbits were normal. A right upper eyelid biopsy was done. Histopathology showed many empty, ectatic, thin-walled vessels consistent with lymphatics [ Fig. 2]. An infl ammatory infi ltrate consisting of lymphocytes and histiocytes was seen surrounding these vessels. One area of section showed intralymphatic histiocytic infi ltration [ Fig.  3]. Immunohistochemistry was positive for CD68 marker confi rming the presence of histiocytes [ Fig. 4]. Quantitative PCR (qPCR) on the paraffi n-embedded skin biopsy specimen was negative for MTb. The excision of a part of eyelid skin improved the patient's appearance and the patient preferred to be under observation [ Fig. 5].

Discussion
In our case, the complete clinical triad of MRS was not present. Although eyelid edema due to MRS is an unusual entity, the clinical fi ndings may be diffi cult to diff erentiate from blepharochalasis or thyroid-associated ophthalmopathy.
There is an isolated report of a possible association with tuberculosis. [3] However, in our case, the paraffi n-embedded skin biopsy specimen did not demonstrate the MTb antigen by qPCR. The association in our case with tubercular panuveitis may be casual. Treatment is challenging and includes intralesional usage of corticosteroids and or oral treatment with dapsone, clofazimine, tetracycline, clindamycin and methotrexate without any reproducible improvement. A combination of surgical debulking and intralesional steroid therapy has been advocated to improve cosmesis. Because of its rarity, this syndrome is usually ignored and misdiagnosed. MRS may be considered in all cases of isolated eyelid edema and a diagnostic incision biopsy may be performed to establish a diagnosis.