ocelot

I am posting this because I have finally (after 20 years!) for the first time received a diagnosis for an unusual set of symptoms that may be of interest to many anemic individuals diagnosed with autoimmune disorders.

I have macrocytosis (enlarged red cells), deteriorating red cell counts, low platelet volume and plateletcrit, large and giant platelet forms and, more recently, teardrop red cells and fragments of megakaryocytes (platelet precursor cells) on the blood smear. I also have had an unidentified autoimmune disease with constitutional symptoms (night sweats, body aches, malaise) resembling microangiopathic vasculitis (intermittent bleeding under the fingernails and in the kidneys), seronegative tenosynovitis and arthritis, as well as intermittent low levels of various immunoglobulins (A and G subgroup 2) for over twenty years.

Last week my hemo gave me the first provisional diagnosis that actually fits all of the symptoms and history, and which is accordingly obscure. It is primary autoimmune myelofibrosis (PAIF), an autoimmune mediated proliferation of lymphocytes, megakaryocytes and reticulin fibers in the bone marrow caused by atypical autoimmune disease. It suggests that the immune system (the B and T lymph cells, in particular) are aggregating in the marrow and and producing autoantibodies to cells, proteins or other molecules found in the marrow that are disrupting the function of marrow fibroblasts, erythroblasts and megakaryocytes. The fibers progressively destroy the bone marrow, resulting in eventual bone marrow failure. Untreated, the condition results in increasing pancytopenia (shortages of red, white and platelet cells) and resulting mortality due to beeding, infection or hypoxia.

The good news is that it can be controlled. The bad news is that treatment is with lifelong corticosteroids and, if required, chemotherapy. The differential diagnosis includes myelodysplastic syndrome, idiopathic myelofibrosis, acute myelofibrosis, CML, CLL, hairy cell leukemia, various lymphomas and acute megakaryoblastic leukemia (AML M7). I doubt any of those are present as my LDH and other typical signs of malignancy have remained normal.

This disease has remained underrecognized until recently because it effectively hides in the bone marrow, away from most rheumatologists' and other doctors' eyes. Rheums often don't recognize the seriousness of autoimmune features that don't fit neatly into the usual rheum diagnostic diseases. They also usually won't subject their patients to bone marrow biopsies or otherwise take very seriously the initially mild cytopenias that result as the myelofibrosis begins damaging the bone marrow, partly because they employ so many medications that cause those symptoms and thus assume the low blood counts are merely drug side effects (mine was so unconcerned with my relatively mild tenosynovitis and vasculitis that he took me off of plaquenil earlier this year, resulting in increased inflammation in my shoulders and all extemities; to be fair he also thought, plausibly, that the macrocytosis could be a side effect of the plaquenil). Significantly, these cytopenias are also regular findings in SLE, scleroderma, Sjogren's and other well-defined autoimmune conditions, and may often be caused by unrecognized autoimmune myelofibrosis (under those circumstances it may be characerized as secondary AIF).

Diagnosis requires high quality bone marrow biopsy and hematopathologic analysis (including complicated specimen staining, flow cytommetry, karyotyping and immunohistochemical analysis). In view of the condition's obscurity and the differential diagnosis, which includes a very dangerous form of leukemia (AML M7), I recommend finding a nationally recognized hematology-oncology practice associated with a national cancer laboratory to do the review. I will probably have my research-oriented Atlanta hemo-onco do the biopsy, but plan to get a second opinion on the diagnosis at Sloan Kettering in NYC or Anderson in Houston.

Best of luck.