Characteristics of Sarcoidosis-Associated Immune Thrombocytopenia: a Consecutive Study of 20 Cases.

Although sarcoidosis is far from being a classical cause of secondary-immune thrombocytopenic purpura (ITP), isolated thrombocytopenia may occur during the course of the disease. To better assess the main characteristics and outcome of patients with a sarcoidosis-associated ITP, a survey was initiated throughout the French study group on sarcoidosis and the national referral center for adult's immune cytopenias. The data of the 20 first cases are reported.

To be included, all patients had to fulfil the following criteria: 1) Definite diagnosis of sarcoidosis according to the standard international criteria (Am J Respir Crit Care Med 1999; 736-55) and 2) Presence of an immune thrombocytopenia according to the ASH criteria twith platelet count below 100 × 10⁹/L on at least two separate occasions 2 weeks. Drug-induced thrombocytopenia were excluded as well as patients with a hypogammaglobulinemia suggesting a underlying common variable immunodeficiency (CVI) and thrombocytopenia related to hypersplenism. All clinical and biological data were reviewed and analyzed by the same investigator by using a standard form. A complete response (CR) was defined as sustained (> 3months) platelet count > 100 × 10⁹/L with at least a twofold increase for baseline. A partial response (PR) was defined as a platelet count 30×10⁹/L or more and at least twice the initial value.

Twenty patients (50% men) were included. Median age at ITP diagnosis was 37.5 years (21 to 83) and median age at sarcoidosis diagnosis was 36 yrs (10 to 83). In 4 patients, ITP preceded the diagnosis of sarcoidosis (median: 67.5 months; 15 to 153). In 11 patients (55%), ITP occurred in the course of prior diagnosed sarcoidosis with a median of 48 mths (6 to 216), and concomitantly with the diagnosis of sarcoidosis in 5 patients (25%). In 13 patients (65%), an active localization of sarcoidosis was present at the diagnosis of ITP. Median platelet count at onset was 11×10⁹/L (3 to 90) and nadir platelet count was 10×10⁹/L (1 to 60). Seven patients (35%) had severe (mucosal) bleeding manifestations and a bleeding score ≥ 8 (described by Khellaf et al). Regarding sarcoidosis, during the follow up, 17 patients (85%) had thoracic involvement, and an extra-thoracic involvement was found in 14 patients (70%) including: eye (n=7), liver (n=5), sinus (n=4), peripheral lymph nodes (n=4), skin (n=3), salivary gland (n=2), spleen (n=1) and kidney (n=1).

Nineteen out of the 20 patients were treated specifically for their secondary ITP. After the first line therapy (prednisone at 1mg/kg/day for at least 3 consecutive weeks in all patients associated with IVIg in 10 patients), 12/19 (63%) patients achieved a complete response (CR), 6 a partial response (PR) (32%) and only 1 patient failed to respond. The course of ITP was chronic in 4 patients, among them 2 underwent splenectomy and achieved a CR and 2 were treated with Rituximab (375mg/m², 4 infusions) and achieved a PR at one year. After a median follow up of 70 months (12 to142), 18 patients (90%) were in CR and 2 in PR with chronic ITP. Eight patients were in remission off therapy whereas 12 patients (60%) were still on corticosteroids at time of analysis with a median dose of 10mg/day (5 to 30). During the follow-up period, 11 patients (55%) had a relapse or flare of sarcoidosis (intra thoracic in 5 patients, extra-thoracic in 6 patients). In 2 patients, a simultaneous relapse of both sarcoidoisis and associated-ITP was observed.

Our preliminary data suggest that the association of sarcoidosis and ITP is not fortuitous and that sarcoidosis should be considered as a potential cause of secondary ITP. ITP in this setting is frequently initially severe and symptomatic and therefore requiring treatment. The overall response rate to treatments commonly used in primary ITP is however good and the long term outcome is favorable suggesting that patients with sarcoidosis-associated ITP should be managed as patients with primary ITP. In contrast, relapse of sarcoidosis is frequent and frequently affect extra-thoracic sites. That a majority of the patients had an active and/or relapsing sarcoidosis during the course of ITP suggests that granuloma may be a predisposing condition for triggering autoimmunity and especially ITP as observed in some cases of CVI-associated immune thrombocytopenia.

No relevant conflicts of interest to declare.