the simultaneous or sequential development of autoimmune hemolytic anemia ( aiha ) and immune thrombocytopenia ( itp ) and/or immune neutropenia in the absence of any underlying cause was described as the evans syndrome ( es ) by evans et al . , in 1951 . since its first description ,
es was considered as an idiopathic condition , and mainly as a diagnosis of exclusion .
however , few case reports showed a common association of es with other diseases , such as , systemic lupus erythematous , lymphoproliferative disorders , and immunodeficiency , which warranted the classification of es into primary and secondary .
only three case reports of the association of evans syndrome with hashimoto 's thyroiditis were found in the literature review , and to the best of our knowledge , this is the fourth case , with a complete evaluation .
a 34-year - old female , who is a known case of hashimoto 's thyroiditis , on synthetic thyroid hormone intake ( 50 g / day ) since five years , presented with high - grade intermittent fever associated with chills and rigors , headache , and breathlessness .
there was no significant family history of thyroid disease and she was on no other medication except for the thyroxine intake . on examination ,
her blood pressure was 110/90 mm of hg , body temperature was 101f , and pulse rate was 120 per minute .
she had minimal , firm thyromegaly , tenderness in the right hypochondrium , and mild splenomegaly , on an ultrasound scan of the abdomen .
there were neither enlarged peripheral lymph nodes nor any enlargement of them on the abdominal ultrasound scan .
further investigations were negative for malaria , hepatitis b surface ( hbs ) antigen , hepatitis c virus ( hcv ) antibody , dengue , hiv , syphilis , and leptospirosis .
she had low hemoglobin , hematocrit , red blood cells ( rbc ) , and platelet count along with high mean corpuscular volume ( mcv ) .
peripheral blood smear examination showed a marked anisocytosis comprising of macrocytes , polychromatic cells , and microspherocytes .
a high percentage of nucleated rbc and thrombocytopenia were also seen [ figure 1 ] .
peripheral blood smear shows features of hemolysis manifested as spherocytes , macrocytosis , nucleated rbc , and polychromatic cells along with thrombocytopenia ( 400 ) bone marrow aspiration was done to rule out any underlying lymphoproliferative conditions and the slides showed only hypercellular marrow with erythroid hyperplasia and increased megakaryopoiesis [ figure 2 ] .
the overall impression on hematological examination was hemolytic anemia with thrombocytopenia and reactive marrow hyperplasia .
to summarize , the patient had a positive direct antiglobulin test , evidence of hemolysis in the form of reticulocytosis , elevated indirect bilurubin , and serum lactate dehydrogenase ( ldh ) .
the constellation of the clinical and laboratory data suggested that the patient was a case of hashimoto 's thyroiditis complicated by evans syndrome .
her present hemoglobin is 13.2 grams% and total serum bilirubin is 0.8 mg / dl .
autoimmune diseases comprise of a heterogeneous group of disorders and are sometimes defined as a clinical syndrome caused by alterations in the immune system such as activation of t cells or b cells or both , resulting in a spectrum of diseases that can target specific organs or affect the body systemically .
autoimmune thyroid diseases , thus comprise of a series of interrelated conditions including hyperthyroid graves disease , hashimoto 's thyroiditis , atrophic autoimmune hypothyroidism , postpartum thyroiditis , and thyroid - associated ophthalmopathy .
the initiation of autoimmune events in hashimoto 's thyroiditis may be caused by a molecular mimicry mechanism , abnormal antigen - specific induction of t cells due to abnormal human leukocyte antigen ( hla)-related genes , mutation of t cells to form abnormal clones , or an immune defect causing reduced induction of t - suppressor cells by specific antigens .
the detection of anti - thyroid peroxidase ( tpo ) is one of the reliable diagnostic tests for hashimoto 's thyroiditis ( ht ) and our patient showed a high antibody level .
the diagnostic features of autoimmune hemolytic anemia include a combination of clinical and laboratory signs of rbc hemolysis , together with the detection of autoantibodies , as represented mostly by a positive direct antiglobulin test ; which has been demonstrated in our case
. the formation of autoantibodies in autoimmune hemolytic anemia ( aiha ) may be due to the break down in t - cell regulation of b cells , with the emergence of a hostile clone of immunocytes , or to a change in the structure of the antigen on the patient 's red cells , which is then recognized as non - self by its immune system .
a rise in serum bilirubin greater than 5 mg / dl seldom occurs in uncomplicated hemolysis unless hepatobiliary disease is also present , however , increased bilirubin with normal alkaline phosphatase suggests constitutional hyperbilirubinemias or hemolytic crisis . an elevated aspartate transferase ( sgpt ) alone can be of nonspecific etiology , such as , anemia .
patients with isolated unconjugated hyperbilirubinemia ( gilbert 's syndrome ) may develop more pronounced hyperbilirubinemia in intercurrent illness , such as , febrile illness .
we attribute the high bilirubin and altered serum glutamic pyruvate transaminase ( sgpt ) noted in our patient to hemolytic crisis and anemia
. we could not evaluate the hepatic conjugating enzyme uridine diphosphate glucuronyl transferase in our case , to exclude gilbert 's disease .
the clinical presentation of febrile illness , hyperbilirubinemia , and hemolytic crisis , with relatively normal liver function tests , as a scenario in our case , has provocated us to exclude a previously unrecognized gilbert 's syndrome in the follow - up .
there is a diversity of autoimmune mechanisms in idiopathic thrombocytopenic purpura ( itp ) , such as , antiplatelet antibodies and b - cell , and t - cell tolerance .
platelet antibodies are only detected in approximately 60% of the patients and failure to detect may be due to limited test specificity or undetected antigens . the immune tolerance defects in itp can arise during early development ( central tolerance defects ) , due to differentiation blocks with skewed peripheral b - cell subsets or peripheral tolerance defects arising in the setting of immune stimulation .
a negative antiplatelet antibody in our case may be due to the above - mentioned reasons and in cases of concomitant active aiha , the presence of mild splenomegaly is not an exclusion criterion for itp .
approximately 2% of the patients with itp have coexisting immune hemolytic anemia ( evans syndrome ) .
however , in clinical practice true cases of es may show a variety of underlying diseases , and thus , es should be classified as primary or secondary .
the increased relative risk of acquiring a second autoimmune disease may be due to a genetic susceptibility that affects both diseases , the alteration of the body 's homeostasis by one disease that creates a susceptibility to another or some as - yet undefined shared mechanism .
the present case is a rare clustering of three autoimmune diseases ; hashimoto 's thyroiditis , autoimmune hemolytic anemia , and immune thrombocytopenia , and can be attributed to any of the above - mentioned causes .
polyglandular autoimmune syndromes ( pgas ) are rare immune endocrinopathies characterized by the coexistence of at least two endocrine gland insufficiencies , and associations with nonendocrine immune diseases may occur . the serum electrolytes and glucose levels of the patient had been normal , thus ruling out adrenal insufficiency in our case .
organ - specific autoantibody screening facilitates the identification of those that are at risk of developing pgas . in view of financial constraints
we have not been able to screen for all the organ - specific autoantibodies , but the patient is kept under regular follow - up .
detection of such cases needs close collaboration and good communication between the laboratory physician and the clinician .
patients with clustered autoimmunological diseases necessitate evaluation over time , and detection of various organ - specific antibodies as well as hla - gene polymorphisms , will broaden the entities under autoimmune polyendocrine syndromes .
 evans syndrome is a rare combination of autoimmune hemolytic anemia and immune thrombocytopenia . 
 their association with autoimmune thyroid diseases has been reported by few authors ; however , a sequential development of the evans syndrome in cases of hashimoto 's thyroiditis is extremely rare . 
 the clustering of these autoimmune diseases might share a common pathogenic pathway . 
 we present the fourth such case in world literature , of a 34-year - old female diagnosed with hashimoto 's thyroiditis in 2006 , who has been taking synthetic thyroid hormone since then . 
 her condition is now clinically complicated with the development of the evans syndrome . 
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