Evans syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2] Fizza Zulfiqar, MD[3]

Evans’ Syndrome is an autoimmune disease in which an individual’s antibodies attack their own RBCs as well as their platelets. Its overall pathology is therefore effectively a combination of the two autoimmune induced conditions: autoimmune hemolytic anemia and immune thrombocytopenic purpura. Autoimmune hemolytic anemia is a condition in which the red blood cells that normally carry oxygen and carbon dioxide are destroyed by an autoimmune process. Immune thrombocytopenic purpura is a condition in which the platelets in the blood are destroyed by an autoimmune process. Platelets are a component of blood that contribute to the formation of blood clots in the body to prevent bleeding. Patients with Evans syndrome usually appear normal. Physical examination of patients with Evans syndrome is usually remarkable for jaundice, hepatosplenomegaly, and lymphadenopathy. Laboratory findings consistent with the diagnosis of Evans syndrome include anemia, direct coombs test positive, and antineutrophil antibody positive. Pharmacologic medical therapies for Evan’s syndrome include prednisone, intravenous immunoglobulin, and rituximab. Surgery is not the first­line treatment option for patients with Evans syndrome. Splenectomy is usually reserved for patients who are unresponsive to treatment.

Evans syndrome was first described by Dr. Robert S. Evans, an American physician, in 1951. Evans suggested that thrombocytopenia was likely due to an autoantibody directed against the platelets.

The exact pathogenesis of Evans syndrome is not fully understood. It is thought that Evans syndrome is an autoimmune disorder in which autoantibodies are produced against red blood cells and platelets mainly, but also antibodies can be found against neutrophils and lymphocytes.It is also called “immune pancytopenia”.^[1] On gross pathology, circumscribed mass with microscopic infiltration is a characteristic finding of Evans syndrome. On microscopic histopathological analysis, the alternating fibrous and myxoid stroma of low-grade/low malignant potential, and small tumor cells with scanty eosinophilic cytoplasm with a round to oval nuclei and no nucleoli are characteristic findings of Evans syndrome.

The cause of Evans syndrome has not been identified. It is assumed that excess immune dysregulation is the probable cause of Evans Syndrome.^[2]

Evans syndrome must be differentiated from acquired thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, Kasabach-Merritt syndrome, fibromatosis, fibrosarcoma, myxofibrosarcoma, nodular fasciitis, and myxoid neurofibroma. Other differential diagnosis includes: Vitamin defficiencies, Paroxysmal nocturnal hemoglobinuria (PNH) or HELLP (hemolysis-elevated liver enzymes – low platelets) seen in pregnancy.^[3]

The incidence of Evan’s Syndrome is not precisely known. Evan’s Syndrome affects males and females equally. Evan’s Syndrome is a rare disease that tends to affect children.

Any history of malignancy, positive family history, and presence of the immune defect.

If left untreated, patients with Evans syndrome have periods of exacerbation. Common complications of Evans syndrome include thrombocytopenia and autoimmune hemolytic anemia. Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as good.

Symptoms of Evans syndrome include breathlessness, fatigue, jaundice, dark urine, pallor, weakness, petechiae, ecchymosis, and epistaxis.

Due to prolonged immune suppressive therapies they are more prone to respiratory tract infections.^[4]

Patients with Evans syndrome usually appear normal. Physical examination of patients with Evans syndrome is usually remarkable for jaundice, hepatosplenomegaly, and lymphadenopathy.

Laboratory findings consistent with the diagnosis of Evans syndrome include anemia, direct Coombs test positive, and antineutrophil antibody positive.

Following tests are indicated for the diagnosis of Evans’s syndrome: Complete blood count, Reticulocyte count, Haptoglobin, LDH, indirect bilirubin, Direct Antiglobulin Test, Monoclonal Antibody Immobilization Platelet Assay (MAIPA), Anti-neutrophil antibodies against CD16/FcγRIII, CD11b, CD35/CR1, CD32/FcγRII^[3]

Pharmacologic medical therapies for Evans syndrome include corticosteroids (prednisone), intravenous immunoglobulin (IVIG), rituximab, anabolic steroids, vincristine, alkylating agents, or cyclosporine.Plasma exchange therapies have also been implicated in its treatment. Refractory disease can be treated by splenectomy and allogeneic hematopoietic stem cell transplant (HSCT).^[5][3]

Surgery is not the first­line treatment option for patients with Evans syndrome. Splenectomy is usually reserved for patients who are unresponsive to treatment.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Evans syndrome was first described by Dr. Robert S. Evans, an American physician, in 1951.

• Evans syndrome was first described in 1951 by Dr. Robert S. Evans and colleagues.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Evans syndrome is an autoimmune disease in which an individual’s antibodies attack their own red blood cells and platelets. The exact pathogenesis of Evans syndrome is not fully understood. On gross pathology, a circumscribed mass with microscopic infiltration is a characteristic finding of Evans syndrome. On microscopic histopathological analysis, alternating fibrous and myxoid stroma of low malignant potential, and small tumor cells with scanty eosinophilic cytoplasm with round to oval nuclei with the absence of nucleoli are characteristic findings of Evans syndrome.

• Although Evans syndrome seems to be a disorder of immune regulation, the exact pathophysiology is unknown.
• Evans syndrome is an autoimmune disease in which an individual’s antibodies attack their own red blood cells and platelets.^[1] Both of these events may occur simultaneously or one may follow the other.^[2]
• Pathophysiology of this disease involves decreased cluster of differentiation (CD)4+ T-helper cell counts, increased CD8+ T-suppressor cell counts, a decreased CD4/CD8 ratio, and reduced serum immunoglobulin G, M and A levels – indicating a complex immune dysregulation.
• Pathology of Evans syndrome resembles a combination of autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura.^[1] Autoimmune hemolytic anemia is a condition in which the red blood cells that normally carry oxygen and carbon dioxide are destroyed by an autoimmune process. Idiopathic thrombocytopenic purpura is a condition in which platelets are destroyed by an autoimmune process. Platelets are a component of blood that contribute to the formation of blood clots in the body to prevent bleeding.
• It has been variously reported that between 10%^[3] to 23%^[4] of patients who have autoimmune hemolytic anemia, will also have thrombocytopenia and thus Evans syndrome. The two features may occur together or sequentially.^[5]
• Depending on the pathophysiology, Evans syndrome can be primary and secondary.

• There are no established causes for Evan’s syndrome. Evans syndrome overlaps with autoimmune lymphoproliferative syndrome.
• Autoimmune lymphoproliferative syndrome is caused by a mutation in the tumor necrosis factor receptor gene superfamily member (TNFRSF6) also called CD95 or Fas gene.

• Autoimmune hemolytic anemia
• Idiopathic thrombocytopenia purpura
• Viral infection^[6]
• Systemic lupus erythematosus
• Hashimoto thyroiditis
• Dermatomyositis
• Chronic inflammatory demyelinating polyneuropathy
• Autoimmune hepatitis

• On gross pathology, circumscribed mass with microscopic infiltration is a characteristic finding of Evans syndrome.

• On microscopic histopathological analysis, Evans syndrome may be characterized by:

• Alternating fibrous and myxoid stroma of low malignant potential
• Small tumor cells with scanty eosinophilic cytoplasm, round to oval nuclei, and no nucleoli

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

The cause of Evans syndrome has not been identified.

The cause of Evans syndrome has not been identified.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Evans syndrome must be differentiated from acquired thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, Kasabach-Merritt syndrome, fibromatosis, fibrosarcoma, myxofibrosarcoma, nodular fasciitis, and myxoid neurofibroma.

• Paroxysmal nocturnal hemoglobinuria (PNH)^[1]
• Acquired thrombotic thrombocytopenic purpura
• Hemolytic-uremic syndrome
• Kasabach-Merritt syndrome
• Fibromatosis
• Fibrosarcoma
• Myxofibrosarcoma
• Nodular fasciitis
• Myxoid neurofibroma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

The incidence of Evan’s Syndrome is not precisely known. Evan’s Syndrome affects male and female equally. Evan’s Syndrome is a rare disease that tends to affect children.

• The incidence of Evan’s Syndrome is not precisely known. The syndrome is reported to be a complication affecting 4-10% of those individuals with a particular type of thrombocytopenia known as idiopathic thrombocytopenic purpura.^[1]

• The syndrome is more prevalent in children than in adults.

• Males and females are affected equally by Evans syndrome.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Faizan Sheraz, M.D. [2] Ammu Susheela, M.D. [3]

If left untreated, patients with Evans syndrome have periods of exacerbation. Common complications of Evans syndrome include thrombocytopenia and autoimmune haemolytic anaemia. Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as good.

• The disease has a chronic course with periods of exacerbation and remissions. The remissions are induced by treatment.

• Thrombocytopenia
• Autoimmune haemolytic anaemia

• The prognosis depends on the patient’s response to treatment. Spontaneous remissions of each of the individual component conditions have been reported. If the child responds well to the treatment and the levels of platelets and red blood cells increase, the child can expect to live a normal life. Medications will be needed life long, and laboratory tests will need to be constantly monitored to detect any abnormal changes so that treatment can be adjusted.
• In more serious cases Evans syndrome can reduce life span and may be seriously life threatening.
• Evan’s Syndrome is rare and has a reported mortality rate of just under 18%.
• It has been observed that there is a risk of developing other autoimmune problems and hypogammaglobulinemia,^[1] with recent research finding that 58% of children with Evans syndrome have CD4-/CD8- T cells which is a strong predictor for having autoimmune lymphoproliferative syndrome.^[2]