Zdrav Vestn | A case of sarcoidosis with hematologic manifestation 861 Abstract A 30 year-old male with a history of pulmonary sarcoidosis presented with relapse and hemato-logic manifestations after successful treatment with corticosteroids and antimycotic itracona-sole for pulmonary sarcoidosis (included in our previous study) is presented herein to discuss possible environmental fungal trigger since high exposure to fungi was found when the activity of mould enzyme β-glucan was measured in his home. Introduction Sarcoidosis is a systemic granulomatous disorder of unknown cause. Haematologic manifestations are rare and may include haemolytic anaemia, leukopenia, eosino- philia and thrombocytopenia.1 Although thrombocytopenia associated with sarcoid-osis was first described in 1938 by Jersilf, the actual frequency is still unknown.2 There is just one report from Maycock et al., who re- ported an incidence of 1,9 % in his review of 324 cases.3 In 1972, Dickerman et al. studied pathophysiological mechanisms of throm-bocytopenia in sarcoidosis and therapeutic possibilities.4 They suggested two patho- physiological mechanisms: increased plate- let destruction by hypersplenism and a pe-ripheral destruction led by auto-immune processes. Mahevas et al. conducted a case study and a thorough review of the literature, and concluded that different mechanisms were responsible. Among them are granulo-mas in the bone marrow, hypersplenism and immune thrombocytopenic purpura. How-ever, other possible mechanisms including viral and Aspergillus infections were also mentioned. 5 Case report A 30-year-old male was diagnosed with sarcoidosis in 2005. From January 2006 to January 2007 he was treated with cortico- steroids for the first time due to exacerba- tion of pulmonary sarcoidosis stage II ; the treatment being gradually discontinued by March 2007. The patient was enrolled in the interventional study of itraconazole in patients with sarcoidosis6 and received itra-Izvleček Pri 30-letnem moškem s preteklo pljučno sarko- idozo (vključen je bil v našo prejšnjo raziskavo) je po uspešnem zdravljenju plučne sarkoidoze s kortikosteroidi in antimikotikom itrakonazo-lom prišlo do ponovitve bolezni in hematoloških sprememb; predstavljeni primer odpira razpra-vo o možnih sprožilnih glivičnih dejavnikih iz okolja, saj je bila ob meritvah aktivnosti encima plesni beta glukana v njegovem bivališču ugoto-vljena visoka izpostavljenost glivam.1 Clinical Departement of Haematology, University Medical Centre, Ljubljana, Slovenia 2 Clinical Department of Pulmolonary Diseases and Allergy, University Medical Centre, Ljubljana, Slovenia Korespondenca/ Correspondence: Irena Preložnik Zupan, Md, Phd , Clinical departement of Haematology, University Medical Centre, Ljubljana, Slovenia Ključne besede: thrombocytopenia, chitotriosidase, β-glucan, itraconazole, hypersplenism Key words: trombocitopenija, hitotriozidaza, β-glukan, itrakonazol, hipersplenizem Citirajte kot/Cite as: Zdrav Vestn 2010; 79: 861–3 Prispelo: 22. maj 2009, Sprejeto: 27. jul. 2009A case of sarcoidosis with hematologic manifestation Primer sarkoidoze s hematološkimi spremembami Irena Preložnik Zupan,1 Marjeta T erčelj,2 Barbara Salobir,2 Matevž Škerget1KlInIčnI PRImeR/CASe RePORT 862 Zdrav Vestn | december 2010 | Letnik 79KLInIčnI PRIMeR/CASe RePORT causative. A combination of all three mech- anisms was probably the cause of throm-bocytopenia in our patient. An excellent response to immunosupresive and antimy- cotic therapy was observed in our patient and a relapse after discontinuation of ther - apy was preceded by a slow increase of ACE levels, a marker of granuloma burden. We suggested that there must be a continuous disturbance in the immune system and/or some yet unidentified environmental agent, which continuously triggers immune reac-tions with granuloma formation. According to our previous experience with antimycotic treatment and relapse of sarcoidosis with systemic and hematologic manifestations in this patient after discontinuation of both an-timycotic and corticosteroid treatment, pro-longed environmental exposure to fungi has been suggested as a possible triggering fac- tor of the disease.6,7 The hypothesis was sup- ported by increased levels of chitotriosidase, an enzyme produced by activated macro-phages involved in the defense against chi-tin containing organisms including fungi, which was recently found to correlate with the activity and progression of sarcoidosis.8,9 Prolonged environmental exposure to fungi has been suggested as a risk factor for sar - coidosis also in previous case-control stud-ies.10 Thus exposure to fungi was measured at his workplace, where a possible source of fungi was old cars’ climate equipment, and was found to be increased. Besides the treat-ment with corticosteroid and antifungal medications, strict antifungal measures in the home environment were advised to pre- vent further relapses of sarcoidosis in this patient.conazole. An excellent response to therapy was observed with complete regression of pulmonary changes and normalisation of se-rum angiotensin converting enzyme (ACE) levels during treatment. However, already at tapering of the therapy with corticosteroids, ACE levels started to increase and were again increased above normal levels after discon-tinuation of the therapy (ACE on start, dur - ing and after discontinuation of therapy: 0.56 µKat/L, 0.19 µKat/L, and 0.63 µKat/L; reference value 0.13–0.47 µKat/L). In May 2008 he was admitted to the haematology department with severe thrombocytope-nia (platelet count 4 x 109/L) and multiple petechiae on both legs and in the oral cav-ity. The complete blood count and blood smear were normal (leukocyte count was 5.9 x 109/L, haemoglobin level was 144 g/L). Coagulation screening tests and infectious parameters were negative. There was no fe- ver, coughing, dyspnoea or pain; urine and stool were without changes. At that time he was receiving no medication. Chest X-ray showed nodules in lung parenchyma without enlarged mediastinal lymph nodes. Ultrasound of the abdomen showed an en- larged spleen and enlarged retroperitoneal lymph nodes. A bone marrow aspirate and a biopsy specimen showed sarcoid nodules in the bone marrow. Treatment with high doses of corticosteroids was started and was suc- cessful. Laboratory investigations showed increased ACE (0.50 µKat/L) and chitotrio- sidase (825 nmol/h/mL) and normalization during treatment: ACE (0.17 µKat/L) and chitotriosidase (17.8 nmol/h/mL). In addi- tion β-glucan activity was measured at his working place, where he was working with old cars’ climate equipment. The activity was high: 9.2 ng/m3 as compared to 0–2.5 U/m3 usually found inside buildings. discussion and conclusion Different pathophysiologic mechanisms are responsible for haematologic changes in patients with sarcoidosis and thrombocyto- penia. Besides auto-immune thrombocyto- penic purpura, bone marrow involvement with granulomatous infiltration and spleen enlargement with hypersplenism may be Zdrav Vestn | A case of sarcoidosis with hematologic manifestation 863KLInIčnI PRIMeR/CASe RePORT 7. Tercelj M, Salobir B, Rylander R. Microbial anti- gen treatment in sarcoidosis – a new paradigm. Med Hypotheses 2008; 70: 831–4. 8. Tercelj M, Salobir B, Wraber B, Simcic S, Rylander R. Chitotriosidase activity in sarcoidosis and some other pulmonary diseases. Scand J Clin Lab In- vest. 2009; 69: 575–8. 9. Grosso S, Margollicci MA, Bargagli E, Buccoliero QR, Perrone A, Galimberti D, et al. Serum levels of chitotriosidase as a marker of disease activity and clinical stage in sarcoidosis. Scand J Clin Lab Invest 2004; 64: 57–62. 10. Newman LS, Rose CS, Bresnitz EA and the AC-CESS Research Group. A case control etiologic study of sarcoidosis: environmental and occu- pational risk factors. Am J Respir Crit Care Med 2004; 170: 1324–30.References 1. Judson MA. Extrapulmonary sarcoidosis. Semin Respir Crit Care Med 2007; 28: 83–101. 2. Jersilf M. The syndrome of Herfordt (Uveo-parot-id fever), a manifestation of Boeck’s sarcoid. Acta Med 1938: 322–6. 3. Maycock RL, Bertrand P , Morrison CE, Scott JH. Manifestations of sarcoidosis. Am J Med 1963; 35: 67–89. 4. Dickerman JD, Holbrook PR, Zinkham WH. Eti-ology and therapy of thrombocytopenia associ-ated with sarcoidosis. J Pediatr 1972; 81: 758–64. 5. Mahevas M, Le Page L, Salle V , Lescure FX, Smail A, Cevallos R, et al. Thrombocytopenia in Sar - coidosis. Sarcoidosis Vasc Diffuse Lung Dis 2006; 23: 229–35. 6. Tercelj M, Rott T, Rylander R. Antifungal treat- ment in sarcoidosis—a pilot intervention trial. Respir Med 2007; 101: 774–8.