|Ahead of print publication
Behcet's diseases' coexistence with idiopathic thrombocytopenic purpura
Saloni Abhijit Desai, Uddhao S Zambare, Chitra S Nayak
Department of Skin and V.D., TNMC and BYL Nair Ch. Hospital, Mumbai, Maharashtra, India
|Date of Submission||16-Apr-2020|
|Date of Decision||04-Jun-2020|
|Date of Acceptance||24-Jul-2020|
Saloni Abhijit Desai,
Department of Skin and V.D., TNMC and BYL Nair Ch. Hospital, Mumbai - 400 008, Maharashtra
Source of Support: None, Conflict of Interest: None
Behcet's disease (BD) is a chronic multisystem disorder characterized by a triad of oral ulcers, genital ulcers, and uveitis. Association between BD and other autoimmune disorders is not well documented. BD with idiopathic thrombocytopenic purpura has rarely been reported. Here, we present the case of a 16-year-old female presenting with recurrent oral and genital ulcers with a low platelet count diagnosed as BD with idiopathic thrombocytopenic purpura based on clinical and laboratory findings. The patient showed an excellent response to systemic corticosteroids.
Keywords: Behcet's disease, Idiopathic thrombocytopenic purpura,corticosteroids
| Introduction|| |
Behcet's disease (BD) is a poly-symptomatic systemic vasculitis disorder with a relapsing and remitting course, caused by genetic and environmental factors. It is characterized by a triad of oral ulcers, genital ulcers, and cutaneous manifestations and is diagnosed as per the Indian study group criteria, 1990.
Although the pathology of BD involves vascular injury, the autoimmune responses with circulating immune responses are thought to be responsible for the mucocutaneous lesions. Association between BD and other autoimmune disorders is not well documented. There are few case reports of its association with Sjogren's syndrome, diabetes insipidus, vitiligo.
To our knowledge, there is only one other case report of BD occurring with idiopathic thrombocytopenic purpura in literature, and none from India.
| Case Report|| |
A 16-year-old female patient came to the Dermatology department with multiple raw lesions on genitals for 10 days, progressively increasing in size. The lesions bled profusely on scratching. She had painful ulcers in the oral cavity for 1 month with a burning sensation during eating. She had an episode of profuse bleeding from the nose 5 days ago, which lasted about 5 min and resolved on applying pressure. On inquiry, she gave accounts of similar lesions in the mouth on and off along with recurrent genital ulcers 1–2 times a month for 2 years. There was neither history of any fluid-filled lesions preceding the ulcers nor any cutaneous lesions.
Examination revealed multiple shallow ulcers on an erythematous base ranging in size from 0.5 cm to 1.5 cm on the vulva and labia minora with bleeding and crusting on the surface. Multiple purpuric macules were present on lower limbs [Figure 1]. The oral cavity had three small superficial ulcers with erythema of surrounding mucosa, ranging in size from 0.2 cm to 0.3 cm at the lower gingivobuccal sulcus below lower incisors.
|Figure 1: (a-c) Multiple shallow ulcers on an erythematous base ranging in size from 0.5 cm to 1.5 cm on the vulva and labia minora with bleeding and crusting on the surface. Multiple purpuric macules were present on lower limbs|
Click here to view
At this stage, differential diagnoses considered were-BD, herpes simplex, aphthous stomatitis, syphilis, and Reiter's disease.
The ocular examination was normal. The patient was anemic with Hemoglobin of 10.8 g/dl, while the platelet count was only 47,000/cmm. White blood cell count was 6200/cmm, and differential counts, as well as peripheral smear, were normal. Bleeding time was raised, clotting time was normal. A pathergy test was performed, which turned out to be negative. Liver and renal function tests, chest X-ray, electrocardiogram, and abdominal ultrasound were all within the normal limits. ELISA for antibodies against HIV, hepatitis C virus (HCV), and hepatitis B surface antigen was nonreactive. Venereal disease research laboratory test was also nonreactive. Immature platelet fraction was found to be raised at 9.2 (normal: 0.7–4.3). A Tzanck smear was performed to look for multinucleated giant cells to rule out herpes simplex and was negative.
Skin biopsy from labia minora lesion showed dense infiltrate in the dermis consisting of neutrophils and few eosinophils along with a predominantly neutrophilic vasculitis [Figure 2]a.
|Figure 2: (a) (H and E, ×100): Dense infiltrate in the dermis consisting of neutrophils and few eosinophils along with a predominantly neutrophilic vasculitis (b) Complete resolution of ulcers over genitals|
Click here to view
A diagnosis of BD with associated idiopathic thrombocytopenic purpura was confirmed on the basis of clinico-pathological correlation. The patient was treated with oral prednisolone 1 mg/kg, i.e., 50 mg, tapered by 10 mg every 2 weeks, along with supportive treatment. Topical anesthetic lidocaine 2% was used before meals for the oral ulcers along with triamcinolone acetonide ointment at night and chlorhexidine mouthwash. The patient showed excellent response with near-complete resolution of ulcers and purpuric lesions on limbs [Figure 2]b. and a rise in platelet count to 262,000/cmm 1 month after starting therapy. The patient was followed up monthly for 6 months and did not have any recurrence of lesions during this period. She was unfortunately lost to follow up after that.
| Discussion|| |
Adamantiades-BD, first described by Hulusi Behcet in 1937, is a chronic multisystem disorder characterized by a triad of oral ulcers, genital ulcers, and uveitis. The exact etiology is unknown, but both genetic and environmental factors have been implicated. Its association with human leukocyte antigens-B51 is well known, especially in patients from North India, and hyper-reactivity against streptococcal antigens or other infective agents such as HCV, herpes simplex virus, and parvovirus 19 is thought to be involved.
The pathology of BD involves vascular injuries and autoimmune responses. Circulating immune complexes and neutrophils appear to be responsible for the mucocutaneous lesions that are characterized histologically by a neutrophilic vasculopathy or vasculitis.
It usually occurs between 20 and 40 years of age. Aphthous stomatitis, the major criterion in International Study Group criteria, appears to be the most common manifestation in Indian patients as confirmed by various studies, followed by genital ulcers and cutaneous lesions. Of the skin manifestations, erythema nodosum is the most common, followed by papulopustular and acneiform lesions. Classic ocular manifestation is acute anterior uveitis, while conjunctival ulcers, retinal vasculitis may lead to long term complications. Our patient presented with characteristic oral and genital ulcers with a relapsing-remitting course but did not have any cutaneous or ocular manifestations.
Histopathology shows lymphocytes, macrophages, and neutrophils are observed at the base of an ulcer with more pronounced infiltrate around the vessels. Although classified as vasculitis, some studies report that most mucocutaneous lesions in BD do not present typical characteristics of an actual vasculitis with fibrinoid necrosis in the vessel walls reported to be very rare.
There is no standard regimen for treatment of BD, and none of the drugs used are curative. Systemic corticosteroids at a dose of 1 mg/kg/day for acute control of symptoms along with immunosuppressants such as dapsone, colchicines, azathioprine, cyclosporine, methotrexate, cyclophosphamide, thalidomide, levamisole, chlorambucil, etc., for long-term use form the mainstay of treatment. Dapsone is a cheap and easily available drug that is often used with good clinical response. Relapse of lesions after the stoppage of steroids remains a challenge, and multiple courses of steroids may be needed.
Idiopathic thrombocytopenic purpura is a diagnosis of exclusion. Almost causes appear to be related to antibodies against platelets, it is also known as immune thrombocytopenic purpura. It has a bimodal age distribution with an acute self-resolving form occurring in children and chronic form occurring in adults. Except for low platelet count, increased bleeding time and raised immature platelet fraction, there are no other abnormalities. Physical signs are only those of bleeding. Secondary causes of thrombocytopenia like leukemia, medications (e.g., quinine, heparin), lupus erythematosus, cirrhosis, HIV, hepatitis C, congenital causes, antiphospholipid syndrome, Von Willebrand factor deficiency, etc., should be ruled out.
Despite being a disorder primarily involving vascular injury and autoimmune responses with circulating immune responses thought to be responsible for the mucocutaneous lesions, association between BD and other autoimmune disorders is not well documented. There are few isolated case reports of BD occurring in patients of Sjogren's syndrome, diabetes insipidus, vitiligo. Thrombocytopenia in the setting of BD may occur due to bone marrow failure or hemolytic uraemic syndrome/thrombotic thrombocytopenic purpura due to cyclosporine therapy, as published in one case report.
A thorough literature search revealed only one other case report of idiopathic thrombocytopenic purpura in a patient of BD. Our case is unique since it is the first such case reported in an Indian patient, and only the second reported case worldwide.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Cebeci F, Onsun N, Pekdemir A, Uras AR, Kayataş K. “Thyroid autoimmunity and Behçet's disease: is there a significant association?” Sci World J 2013;2013:4.
Young SH, Jung NH, Kyoung SJ, Wook KS, Ok LS, Hyuk SD et al
. A case of idiopathic thrombocytopenic Purpura in a patient with Behcet's disease. J Korean Rheumatism Assoc 2005;12:137-42.
Singal A, Chhabra N, Pandhi D, Rohatgi J. Behçet's disease in India: A dermatological perspective. Indian J Dermatol Venereol Leprol 2013;79:199-204. [Full text]
Gündüz Ö. “Histopathological evaluation of Behçet's disease and identification of new skin lesions.” Patholog Res Int 2012;2012:7.
Saleh Z, Arayssi T. Update on the therapy of Behçet disease. Ther Adv Chronic Dis 2014;5:112-34.
Kayal L, Jayachandran S, Singh K. Idiopathic thrombocytopenic purpura. ContempClin Dent 2014;5:410-4.
Chatterjee A, D'Souza RJ. Haemolytic uraemic syndrome during cyclosporin therapy for Behcet's disease. Nephrol Dial Transplant 1997;12:2799-800
[Figure 1], [Figure 2]