systemic lupus erythematosus should be included in the differential diagnosis of every adolescent with pancytopenia . an accurate diagnosis with the appropriate therapy is vital and can cause lasting reversal of this condition . systemic lupus erythematosus should be included in the differential diagnosis of every adolescent with pancytopenia . an accurate diagnosis with the appropriate therapy is vital and can cause lasting reversal of this condition . systemic lupus erythematosus ( sle ) is an autoimmune disease of unknown etiology characterized by the presence of autoantibodies and immune complex deposition . hematological manifestations are very common and are one of the classification criteria of the american college of rheumatology ( acr ) . thrombocytopenia occurs in 2550% of the patients , leucopenia in approximately 50% and coombs ' positive hemolytic anemia in about 10% . they are usually the result of autoantibody - mediated peripheral destruction with associated hypercellular bone marrow . although hematological manifestations are common , they are seldom the sole presenting feature of the disease . most often , cytopenias appear during the course of the disease , but occasionally aplastic anemia is the initial manifestation of sle [ 47 ] . this may be underestimated due to the presumed peripheral destruction of the blood cells . in this paper , we describe 2 adolescents with aplastic anemia as the presenting feature of pediatric sle . full functional inquiry was normal , but her parents had noticed photosensitivity of the face especially in the summer at a young age . she was born in canada ; her parents are of asian descent and are non - consanguineous . physical examination revealed a malar rash , three caf - au - lait spots , but was otherwise normal without lymphadenopathy , hepatosplenomegaly or arthritis . laboratory examination showed a platelet count of 23  10/l , white cell count of 3.9  10/l with absolute neutrophil count ( anc ) 1.34  10/l , lymphocyte count 1.41  10/l , and hemoglobin 147 the international normalized ratio ( inr ) was 1.0 and the partial thromboplastin time ( ptt ) was 26 sec . g / l and 5.6 g / l , respectively , with a normal igm at 1.0 antinuclear antibody ( ana ) was positive at 1:160 but anti - double stranded dna , rheumatoid factor , anti - sm , anti - rnp , anti - ro , and anti - la antibodies were all negative . anticardiolipin antibodies were equivocal by enzyme - linked immunosorbent assay , but lupus anticoagulant was negative . spontaneous and induced ( mmc ( mitomycin c ) , deb ( diepoxybutane ) ) chromosomal breakage studies , to exclude fanconi anemia , were not elevated . bone marrow aspiration and trephine biopsy ( narrow , cylindrically shaped solid piece of bone marrow ) revealed a hypocellular marrow with a cellularity of less than 20% ( fig.1 ) . bone marrow biopsy is revealing hypocellular marrow with a cellularity of far less than 20% ( case 1 ) . she fulfilled the classification criteria for sle ( photosensitivity , a malar rash , hematologic criteria and immunologic criteria [ positive ana ] ) and a diagnosis of sle was made . hydroxychloroquine 300 mg once daily was started , and her blood counts have gradually improved . laboratory examination after 2 years showed a platelet count of 105  10/l , anc 1.84  10/l , and hemoglobin 128 functional inquiry revealed a history of resolved hepatitis of unknown etiology ( all viral studies were negative and no toxins or reactions to medication were noted ) 1 year previously . physical examination revealed bruises and petechiae ; the remainder was unremarkable without lymphadenopathy , hepatosplenomegaly or arthritis . laboratory examination showed a platelet count of 31  10/l ( lowest 12  10/l ) , hemoglobin of 135 g / l , and white blood cell count of 3.5  10/l with an anc of 1.31  10/l . he had a normal urinalysis with normal renal , liver function , serum immunoglobulins , and mildly elevated c-3 complement . bone marrow examination showed a hypocellular marrow , consistent with aplastic anemia ( fig.2 ) . bone marrow biopsy showed hypocellular marrow , consistent with aplastic anemia ( case 2 ) . he was treated with a short course of prednisone and ivig ( intravenous imunoglobulin ) under the suspicion of acute itp ( idiopathic thrombocytopenic purpura ) , and a mild improvement on the platelet count was noticed , but he developed normocytic anemia with absolute reticulocyte count of 65  10/l and neutropenia . over the ensuing months he complained of bilateral wrist pain with swelling and morning stiffness with no other new symptoms . the only change in laboratory blood work was a positive ana at a titer of 1:40 and positive anti - ro antibodies but negative anti - double stranded dna , anti - sm , anti - rnp , anti - la antibodies , and rheumatoid factor . his c-3 complement was still mildly elevated , while his c-4 complement level was normal . physical examination was remarkable for a malar rash , some palatal petechiae , and polyarthritis . on the basis of a malar rash , arthritis , and the hematologic and immunologic criteria , he fulfilled the classification criteria for sle and a diagnosis of sle was made . prednisone at 20 mg once daily and hydroxychloroquine 400 mg once daily were started and after several weeks marked clinical improvement was noted . his follow - up blood counts revealed a normal hemoglobin and white blood cell count with an improvement in the platelet count to > 50  10/l . full functional inquiry was normal , but her parents had noticed photosensitivity of the face especially in the summer at a young age . she was born in canada ; her parents are of asian descent and are non - consanguineous . physical examination revealed a malar rash , three caf - au - lait spots , but was otherwise normal without lymphadenopathy , hepatosplenomegaly or arthritis . laboratory examination showed a platelet count of 23  10/l , white cell count of 3.9  10/l with absolute neutrophil count ( anc ) 1.34  10/l , lymphocyte count 1.41  10/l , and hemoglobin 147 the international normalized ratio ( inr ) was 1.0 and the partial thromboplastin time ( ptt ) was 26 sec . g / l and 5.6 g / l , respectively , with a normal igm at 1.0 antinuclear antibody ( ana ) was positive at 1:160 but anti - double stranded dna , rheumatoid factor , anti - sm , anti - rnp , anti - ro , and anti - la antibodies were all negative . anticardiolipin antibodies were equivocal by enzyme - linked immunosorbent assay , but lupus anticoagulant was negative . spontaneous and induced ( mmc ( mitomycin c ) , deb ( diepoxybutane ) ) chromosomal breakage studies , to exclude fanconi anemia , were not elevated . bone marrow aspiration and trephine biopsy ( narrow , cylindrically shaped solid piece of bone marrow ) revealed a hypocellular marrow with a cellularity of less than 20% ( fig.1 ) . bone marrow biopsy is revealing hypocellular marrow with a cellularity of far less than 20% ( case 1 ) . she fulfilled the classification criteria for sle ( photosensitivity , a malar rash , hematologic criteria and immunologic criteria [ positive ana ] ) and a diagnosis of sle was made . hydroxychloroquine 300 mg once daily was started , and her blood counts have gradually improved . laboratory examination after 2 years showed a platelet count of 105  10/l , anc 1.84  10/l , and hemoglobin 128 a 15-year old boy presented with bruising and petechiae . functional inquiry revealed a history of resolved hepatitis of unknown etiology ( all viral studies were negative and no toxins or reactions to medication were noted ) 1 year previously . physical examination revealed bruises and petechiae ; the remainder was unremarkable without lymphadenopathy , hepatosplenomegaly or arthritis . laboratory examination showed a platelet count of 31  10/l ( lowest 12  10/l ) , hemoglobin of 135 g / l , and white blood cell count of 3.5  10/l with an anc of 1.31  10/l . he had a normal urinalysis with normal renal , liver function , serum immunoglobulins , and mildly elevated c-3 complement . bone marrow examination showed a hypocellular marrow , consistent with aplastic anemia ( fig.2 ) . bone marrow biopsy showed hypocellular marrow , consistent with aplastic anemia ( case 2 ) . he was treated with a short course of prednisone and ivig ( intravenous imunoglobulin ) under the suspicion of acute itp ( idiopathic thrombocytopenic purpura ) , and a mild improvement on the platelet count was noticed , but he developed normocytic anemia with absolute reticulocyte count of 65  10/l and neutropenia . over the ensuing months he complained of bilateral wrist pain with swelling and morning stiffness with no other new symptoms . the only change in laboratory blood work was a positive ana at a titer of 1:40 and positive anti - ro antibodies but negative anti - double stranded dna , anti - sm , anti - rnp , anti - la antibodies , and rheumatoid factor . his c-3 complement was still mildly elevated , while his c-4 complement level was normal . physical examination was remarkable for a malar rash , some palatal petechiae , and polyarthritis . on the basis of a malar rash , arthritis , and the hematologic and immunologic criteria , he fulfilled the classification criteria for sle and a diagnosis of sle was made . prednisone at 20 mg once daily and hydroxychloroquine 400 mg once daily were started and after several weeks marked clinical improvement was noted . his follow - up blood counts revealed a normal hemoglobin and white blood cell count with an improvement in the platelet count to > 50  10/l . aplastic anemia has been described in patients with sle and is most commonly seen following the diagnosis of sle while presentation before or at the time of diagnosis of sle is unusual   and only a limited number of patients are reported in the pediatric medical literature ( see table 1 ) . in a 2002 review , 17 patients with sle and aplastic anemia ( 13 adults and 4 children ) , wherein the aplastic anemia preceded the diagnosis of sle in only 18% of the cases ( 3 adults ) . since that report , there has been one additional case of aplastic anemia reported at the time of diagnosis in a 22-year - old woman [ 46,9,10 ] . children with lupus who presented with pancytopenia reported in the literature pp , plasmapheresis ; mp , methyl prednisolone ; pred , prednisone ; hchl , hydroxychloroquine . the only previously reported case of aplastic anemia around the time of diagnosis of pediatric sle was in a 6-year old girl with a 3-year history of chronic itp , presenting with fever , arthralgia , oral ulcers , pleuritis , alopecia , and a malar rash . although cyclosporine and antithymocyte globulin are commonly used in idiopathic aplastic anemia ; its use in aplastic anemia associated with sle is very limited and as suggested by our patients , intensive immunotherapy may not be required for sle patients . our patients , with mild pancytopenia , responded to hydroxychloroquine and moderate doses of prednisone and hydroxychloroquine , respectively . this is in contrast to the previous reports in the literature which showed that the majority of cases required a second immunosuppressive agent in addition to oral corticosteroids or pulse methylprednisolone to obtain a response [ 46,9,10 ] . in children , plasmapheresis has been used in addition to corticosteroids , while in adults also cyclophosphamide , azathioprine , and oxymethalone have been used . the long - term outlook after the recovery from aplastic anemia with sle is very good , especially in comparison with idiopathic acquired aplastic anemia . in patients with sle , the immune - mediated cytopenia is secondary to antibodies directed to one or more cell lines resulting in peripheral destruction . however , in our cases and in the previously reported cases of aplastic anemia secondary to bone marrow failure , studies have failed to demonstrate peripheral destruction and in most cases the etiology of the bone marrow failure was not defined . an igg complement - dependent antibody   or a non - complement - dependent antibody suppressing early hematopoietic progenitor cells , but also an auto - immune cellular process inhibiting bone marrow progenitor cells   or a cytotoxic lymphocyte activation suppressing the hematopoiesis   have been proposed . one showed either global hypocellularity or granulocytic hypoplasia   while the other showed stromal bone marrow damage , bone marrow necrosis and dysplasia of all hematopoietic lineages . the latter study did not find a correlation of the severity of peripheral cytopenias with the cellularity and distribution of individual hematopoietic lineages . only limited number of cases of aplastic anemia associated with sle are described in the literature . we suggest that this is likely the result of the presumption that the pancytopenia in sle is always secondary to the peripheral destruction of the blood cells . we therefore suggest that sle should be included in the differential diagnosis of a child with pancytopenia and the appropriate investigations for sle should be undertaken . in addition , as demonstrated by our second case , patients should be serially followed for the subsequent development of sle . similar to what is seen in other sle manifestations , both antibody - mediated and t lymphocyte - mediated mechanisms may lead to the bone marrow failure in sle patients . an accurate diagnosis with the appropriate therapy is vital and can cause lasting reversal of this condition .
key clinical messagesystemic lupus erythematosus should be included in the differential diagnosis of every adolescent with pancytopenia . 
 an accurate diagnosis with the appropriate therapy is vital and can cause lasting reversal of this condition.systemic lupus erythematosus should be included in the differential diagnosis of every adolescent with pancytopenia . an accurate diagnosis with 
 the appropriate therapy is vital and can cause lasting reversal of this condition .