Granulomatous Vulvitis in Association with Takayasu Arteritis

Dear Editor, Granulomatous vulvitis (GV) is clinically characterized by a circumscribed, firm oedema in the vulvar region. This is an uncommon localized inflammatory disease when the vulva is affected by granulomatous inflammation similar to that observed in sarcoidosis, TB, and Crohn’s disease. Here, we present a 36-year-old female with a known case of Takayasu arteritis having vulval swelling for 2 years. The swelling started over the left side of the labia majora and extended to involve the labia minora and peri-anal region. The swelling was associated with itching and frequent appearance of red raised lesions in the last 6 months. There was a history of hospitalization due to fever, fatiguability, and weight loss 8 years back. Relevant history to rule out other causes of chronic genital swelling was negative [Table 1].Table 1: Causes of chronic vulval oedemaOn general examination, the patient had pallor, left absent radial pulse, and a difference of systolic blood pressure greater than 10 mm Hg in both arms (right arm – 120/80 mmHg; left arm – 92/64 mmHg), and lower extremities pulse was found to be regular and normal in volume and character in both limbs. Local examination of the vulva revealed swelling of both labia majora and minora extending to the perianal region. There were few overlying erythematous papules and swelling was non-tender and firm to palpate [Figure 1]. Per vaginal and speculum examination were normal.Figure 1: Swelling of both labia majora and minora extending to the perianal regionOn systemic examination, S1 and S2 were heard, and there was no added murmur. Per abdomen examination revealed no organomegaly or abdominal distension. Chest on palpation and auscultation had normal breath sounds with no crepitations. Investigations revealed haemoglobin (10.8 g/dl) with normal renal and hepatic parameters. CT aortogram revealed narrowing of distal 2/3rd of the left subclavian artery and thrombosis of distal 1/3rd of the right subclavian artery with narrowing of middle 1/3rd of the right subclavian artery. Both upper limb Doppler revealed aortoarteritis involving bilateral subclavian and medium-sized upper arm arteries. The patient was treated with a short course of systemic steroids during the episode which occurred 8 years back and is on tablet clopidogrel 75 mg once a day till date. Chest X-ray and angiotensin converting enzyme levels done to rule out sarcoidosis were normal. HbsAg, HIV, HCV, VDRL, and TPHA were non-reactive. High-frequency local ultrasound revealed diffuse subcutaneous oedema with overlying skin thickening in labia majora. Tissue was taken from labia majora and was sent for cartridge-based nucleic acid amplification test (CBNAAT) and histopathology. In histopathology, the epidermis showed irregular hyperplasia with dense and diffuse mixed inflammatory infiltrate in the dermis composed of many lymphocytes, histiocytes, plasma cells, and an occasional eosinophil. The dermis showed focal collections of epithelioid cell granulomas with multinucleated cells but no caseation. Dermis also showed endothelial cell thickening of blood vessels and perifollicular inflammation [Figure 2]. Sinus tract or dysplasia or fungal colonies or AFB were not evident. Tissue was negative for mycobacterium in CBNAAT.Figure 2: Histopathology showing focal collections of epithelioid cell granulomas with multinucleated cells but no caseation (H&E 40x)We reached to a diagnosis of GV in association with Takayasu arteritis (TA). TA is a large-vessel, granulomatous, idiopathic arteritis that mostly affects the aorta, major branch arteries, and, less frequently, the pulmonary arteries. ‘A granulomatous inflammation of the aorta and its branches “usually” occurring in patients younger than 50 years of age’ is the definition of TA given by the Chapel Hill Consensus Conference. Wall thickening, stenotic or occlusive lesions, and thrombosis are caused by inflammation and intimal proliferation, whereas aneurysms and dissection are the result of the elastica and muscularis layers being destroyed. Large artery wall abnormalities, such as stenosis, aneurysms, occlusion, and signs of increased collateral circulation in angiography, MRA, or CTA imaging, are typically observed to corroborate the diagnosis. It is estimated that skin lesions occur in 2.8% to 28% of TA cases.[1] There can be correlation between TA and GV in terms of chronicity of the cutaneous lesion and the similar histopathological granulomatous mononuclear infiltration shared between both. The common cutaneous manifestations of TA are erythema nodosum (most common), pyoderma gangrenosum, livedo reticularis, facial lupus-like rashes, panniculitis, purpura, cutaneous necrotizing vasculitis, subcutaneous oedema (GV), urticaria, digital gangrene, and ulcers. Skin lesions tend to occur without any relationship without any distribution of vascular involvement; however, pathological findings include granulomatous features which suggests a shared pathogenesis.[1] GV is an uncommon condition that can strike people of any age, even the elderly. It usually starts as an acute inflammatory illness and progresses through a chronic phase of remission and relapses, The vulva enlarges, becomes indurated, and becomes deformed over time. On the vulva and nearby skin, surface lymphangiomas may appear.[2] Oedema, lymphangiectasia, and fibrosis are present. Granulomatous endolymphangitis may occur under specific circumstances. Although a connection to granulomatous illnesses like tuberculosis and sarcoidosis has been proposed, the exact cause of the illness remains unknown. Because these disorders share histologic characteristics with Crohn’s disease, there is a growing recognition of their association. Other documented examples of GV included non-necrotizing granulomas with giant cells and histiocytes that extended to the deep dermis along with a monocytic infiltration.[3] Treatment for granulomatous disorders, like GV, focuses on the inflammatory and autoimmune aspects of the illness in addition to treating its symptoms. This involves the use of topical or intralesional corticosteroids. Acute bouts can be made less severe with the help of systemic corticosteroids. Numerous long-term preventive treatments for GV have been proposed and implemented. These include medications used for their anti-inflammatory rather than their antibacterial properties, such as metronidazole, danazol, clofazimine, and antimalarials.[2] Anti-tumour necrosis factor monoclonal antibodies, such as infliximab and adalimumab, are an additional therapy approach that has demonstrated promising outcomes, particularly in refractory cases. Ultimately, in extreme situations including notable cosmetic deformities, surgical solutions must be taken into account.[4] Oral tranilast was also found to be effective in one case report of GV.[5] The prognosis is unknown, but given the fibrosis and chronic lymphoedema that follow, it is reasonable to assume that the vulva will always be swollen and deformed. We treated our patient with intralesional triamcinolone 10 mg/mL undiluted every 2 weeks which significantly reduced her itching and the softening of the swelling was noticed after three injections, but the results of this therapy are still awaited. We conclude that GV in our patient was in association with TA. Skin lesions in TA tend to occur without any relationship without any distribution of vascular involvement. One of the cutaneous manifestations mentioned in TA is subcutaneous oedema which was seen as chronic vulval oedema in our patient. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.