A 75 year old Caucasian woman, previously diagnosed ET and atrial fibrillation, presented to emergency room with acute on chronic shortness of breath. Her dyspnea was earlier attributed to chronic bronchitis in the absence of evidence of any other pathology. However, this time she had bilateral coarse crackles which correlated with her chest X-ray findings of bilateral interstitial infiltrates. On discussing with her pulmonologist, it was learnt that patient was being evaluated for a working diagnosis of sarcoidosis as evidenced by bilateral interstitial infiltrates and hilar lymphadenopathy on CT scan along with myocardial uptake on FDG-PET scan. Her EKG showed changes suggestive of an old left bundle branch block and an echocardiogram revealed an ejection fraction of 35%. Subsequent biopsy of her pulmonary nodules demonstrated non-caseating granuloma, thus confirming the diagnosis of sarcoidosis. The patient was started on steroids acutely followed by rituximab, which initially helped with keeping her in remission.
In retrospect, much prior to her onset of shortness of breath, this patient was diagnosed with ET with platelet counts of more than 1,000,000 and was found to be JAK-2 mutation positive. On routine evaluation at that point in time she was noted to have small pulmonary nodules of unclear significance. As these nodules were small in size and given the fact that she was asymptomatic from a pulmonary standpoint and a non-smoker by history, outpatient follow-up for these nodules was recommended. In the meanwhile, she was started on treatment with anagrelide followed by hydroxyurea for her ET. Although initially the patient tolerated the treatment with a good platelet response, she started developing shortness of breath after a few weeks of treatment initiation and was eventually diagnosed with sarcoidosis as is detailed above.
Discussion:
Sarcoidosis has been reported in the literature in association with various myeloproliferative disorders. It can precede the onset of MPD by several years, occur concomitantly or develop after initiation of treatment for MPD. There have been case reports of patients with chronic myelogenous leukemia in whom sarcoidosis was precipitated after treatment with interferon. However, there are very few case reports of patients with ET who develop sarcoidosis after treatment with hydroxyurea. We report yet another intriguing case of sarcoidosis developing after treatment with anagrelide and hydroxyurea. It is unclear whether one or both of these medications may have played a role in this occurrence. However, it is likely that the manifestation of sarcoidosis may have been caused by the increased T-cell response of the body to tumor cells, which in our case was related to her ET. This mechanism may have also been exaggerated by further destruction of tumor cells following chemotherapy.
Conclusions:
Sarcoidosis Is a multisystem disorder of unknown etiology, which lately has been observed to occur in association with myeloproliferative disorders (MPD). Essential Thrombocythemia (ET) is a type of MDS characterized by unexplained proliferation of megakaryocytes, which leads to permanent, usually slow, progressive increase in platelet count, typically up to levels of >450,000/microL. There are very few cases of ET occurring in association with sarcoidosis as reported in literature and in a patient with diagnosed myeloproliferative disease presenting with pulmonary complaints this association should be kept in mind.