Congenital Rosai–Dorfman disease presenting with anemia,thrombocytopenia, and hepatomegaly

Rosai–Dorfman disease (RDD) is a rare entity of non‐Langerhans cell histiocytoses (non‐LCH) which usually presents with bilateral painless cervical lymphadenopathy. We describe a neonate with RDD who presented with anemia, thrombocytopenia and hepatomegaly. He recovered spontaneously with conservative management. This represents an atypical presentation of RDD. Conservative management with close monitoring can be adopted for some with systemic involvement. Pediatr Blood Cancer 2009;52:415–417. © 2008 Wiley‐Liss, Inc.     

双阴性T细胞检测在自身免疫性淋巴细胞增生综合征诊断中的重要性：1例报告并文献复习

目的 提高对自身免疫性淋巴细胞增生综合征（ALPS）的认识、减少漏诊,并认识TCRαβ＋ CD3＋ CD4-CD8-T细胞（DNTs）检测在本病诊断中的重要性.方法 对1例ALPS患者资料进行临床分析及文献复习.结果 该例患儿反复发生溶血性贫血、血小板减少.通过颈部淋巴结活检、骨髓形态及病理、染色体核型及DNTs比例、免疫球蛋白定量检测,发现患儿病史长达7年余,反复发生溶血性贫血、血小板减少、淋巴结及肝脾肿大.外周血DNTs比例为8.99％（＞5％）,1gG升高.糖皮质激素治疗有效.结论 临床上出现无法解释的淋巴结肿大、肝脾肿大及自身免疫性溶血、血小板减少的患者应考虑ALPS可能,外周血DNTs比例检测有助于ALPS的早期诊断.     

Recurrent hepatosplenomegaly and peripheral blood cytopenia, persistent Epstein-Barr virus infection and central nervous system manifestation in a patient with lymphadenopathy and low serum uric acid

Abstract We describe a 27-month-old boy who was first admitted to our hospital on 7 January 1995 with nasal bleeding. From 6 months of age he has had lymphadenopathy, low levels of serum uric acid, increased levels of serum lactate dehydrogenase and hyper -y-globulinemia. From the age of 18 months he has had persistent Epstein-Barr virus (EBV) infection (target cells; B cells), recurrent episodes of thrombocytopenia, anemia and hepatosplenomegaly. Dysmobility of the left leg and arm from a central nervous system complication during a relapse with pancytopenia on March 1995, was also observed. Relapses of thrombocytopenia with increases of platelet-associated immunoglobulin G and hepatosplenomegaly have been observed approximately every 2 months, and two relapses of pancytopenia were accompanied with weak positivity of Coombs test and low level of haptoglobin. These recurrent episodes were improved with prednisolone. However, now in June 1997 we have not been able to diagnose what underlies the above clinical symptoms, except that the patient has a persistent EBV infection.     

Unusual presentation of Rosai-Dorfman disease (RDD) in the bone in adolescents

Rosai-Dorfman disease (RDD), or sinus histiocytosis with massive lymphadenopathy (SHML), is a rare idiopathic histiocytic disorder. The usual presentation of RDD is painless bilateral cervical lymphadenopathy. Extranodal RDD with lymphadenopathy occurs in almost 50% of patients but extranodal RDD, without lymphadenopathy, is very rare. Isolated RDD in the bone occurs in only 2% of patients but it is histologically similar to its nodal counterpart. There are only 14 previously reported cases of RDD in the bone without lymph node involvement in children. Here we describe two new patients--one with rib and lung involvement and the other with multi-osseous involvement.     

Trisomy 6 in a childhood acute mixed lineage leukemia

The patient is a 12-year-old boy with acute mixed lineage leukemia (AMLL) and with a rare karyotype of trisomy 6. He was referred to our hospital with gingival swelling, bleeding at the conjunctiva and huge hepatosplenomegaly. Complete blood count revelead leukocytosis with 79% blasts, anemia and thrombocytopenia. Bone marrow examination revealed 82.5% blasts which were morphologically judged as Ml according to the French-American-British classification. Immunophenotyping of leukemic cells showed the presence of CD2, CD7, CD19 and CD13 antigens, suggesting the diagnosis of AMLL. Cytogenetic analysis revealed a single abnormal karyotype of 47, XY,+6, add(15)(q22) which was successfully detected by fluorescence in situ hybridization (FISH) with the probe mapping at the a-satellite region of chromosome 6. Although the patient was treated with several chemotherapy regimens, he could not achieve complete remission and he died of progressive disease 11 months after admission. Fluorescence in situ hybridization analysis was very informative in assessing the residual leukemic cells in interphase during his clinical course.     

Sulfasalazine hypersensitivity with hepatotoxicity, thrombocytopenia, and erythroid hypoplasia

Sulfasalazine, a commonly prescribed drug for the treatment of inflammatory bowel disease, can cause an allergic reaction with hepatotoxicity, lymphadenopathy, and rash. In addition, many hematologic complications have been observed with sulfasalazine, including aplastic anemia, thrombocytopenia, and erythroid hypoplasia. However, thrombocytopenia in association with sulfasalazine hypersensitivity has not been previously reported. We report a child who developed severe thrombocytopenia and anemia during a hypersensitivity reaction to sulfasalazine.     

Visceral leishmaniasis and Coombs' positive hemolytic anemia: a rare association in an infant treated with liposomal amphotericin B

Visceral leishmaniasis is a worldwide, disseminated intracellular protozoal infection that usually manifests by fever, hepatosplenomegaly, anemia, thrombocytopenia, leukopenia and hypergammaglobulinemia. Although anemia is a usual finding, Coombs' positive hemolytic anemia has rarely been reported in association with this disease. Pentavalent antimonials have been the preferred treatment for this disease for decades, but increasing numbers of treatment failure with antimony are being reported. Liposomal amphotericin B is a new drug which is highly efficacious in the treatment of visceral leishmaniasis and produces minimal toxicity. Here we report an infant with visceral leishmaniasis associated with Coombs' positive hemolytic anemia who was successfully treated with liposomal amphotericin B.     

Childhood Kikuchi-Fujimoto disease

To investigate the clinical features of Kikuchi-Fujimoto disease (KFD) and the relationship between viral infection and this disease in children will be better as Kikuchi-Fujimoto disease (KFD) is a lymphadenopathy. The aim of study is to investigate the clinical features of KFD and the relationship. The age, gender, clinical features and aetiopathogenesis of 36 Chinese children with FKD were reviewed, and the viral antigens were detected. Mean age was 10.1 ± 2.8 yr with a male to female ratio of 1.8:1. Fever and lymphadenopathy were the most common complaints, noted in 23 and all cases respectively. Skin rash and hepatosplenomegaly were also noted. Leukopenia, anemia, thrombocytopenia and raised ESR were noted in 21, 6, 4 and 31 cases respectively. Epstein-Barr virus (EBV) IgM and IgG was positive in 1 and 24 of 29 cases respectively. Antigens of EBV and herpes simplex virus 2 (HSV 2) were found in the biopsy tissue section from 2 and 1 case respectively. Autoantibodies were noted in 3 of 15 cases. Steroid hormones were administrated for 19 cases with good efficacy. These results imply that children with lymphadenopathy and/or fever may have KFD and thus excisional biopsy of lymph nodes should be performed earlier on. A hyperimmune reaction of immune cells to EBV and HSV2 may play a role in the pathology of KFD.     

Thrombocytopenic purpura as a presenting manifestation of tubercular lymphadenitis

A 11-year-old girl presented with thrombocytopenic purpura along with cervical lymphadenopathy. There was no hepatosplenomegaly; no evidence of microangiopathy; bone marrow examination was normal. Acid fast bacilli were seen in fine needle aspiration cytology of the lymph node. A diagnosis of tubercular lymphadenitis in association with immune thrombocytopenia was made, and the platelet count recovered with antitubercular therapy. This report illustrates immune thrombocytopenia as a rare manifestation of childhood tuberculosis; the authors also discuss other causes of thrombocytopenia in childhood tuberculosis.     

Angioimmunoblastic Lymphadenopathy with Dysproteinemia: Report of a Case in Infancy with Review of Literature

A case of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) in infancy is reported. The disease had a mild onset with generalized lymphadenopathy, hepatosplenomegaly, thrombocytopenia, polyclonal hypergammaglobulinemia, and T-cell deficiency. The AILD course lasted more than 100 months, alternating clinical remission to recurrent relapses. Hepatitis B viral infection suddenly evolving to hepatic failure was the cause of death. From a rapid survey of the present knowledge, the nosology, immunological features, and therapy of AILD are discussed and a possible presumptive pathogenetic pathway is proposed.     

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): a clinicoradiological profile of three cases including two with skeletal disease

Originally described as sinus histiocytosis with massive lymphadenopathy, Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder with a distinctive microscopic appearance. A rare entity, RDD is often under-diagnosed because of a low index of suspicion by both radiologist and pathologist. Through this article, we wish to apprise radiologists of the spectrum of disease that can be encountered in this disorder. RDD can mimic other common childhood skeletal diseases including benign Langerhans cell histiocytosis and lymphoma. The clinical and radiological manifestations of RDD vary depending upon organ involvement, and its imaging features are often confused with those of other disorders. RDD should be considered in the differential diagnosis of unifocal and multifocal skeletal involvement caused by granulomatous diseases, infections, pseudogranulomatous lesions and malignancy. As long-term outcome is usually good, a conservative approach is justified in most cases. Contrasted with its typical appearance, presenting with bilateral symmetrical cervical adenopathy (as shown in one patient), we also report extranodal involvement of bone in two patients. Extranodal disease occurs along with concomitant nodal disease in about 43% of patients. In 23% of patients, isolated extranodal RDD can be seen, most commonly in the head and neck. In two of our patients, we observed extranodal involvement with skeletal involvement away from the head and neck not associated with lymphadenopathy. Skeletal involvement in RDD without lymphadenopathy is rare, occurring only in 2% of all the patients reported to date.     

Faisalabad histiocytosis mimics Rosai-Dorfman disease: brothers with lymphadenopathy, intrauterine fractures, short stature, and sensorineural deafness

Rosai-Dorfman disease (RDD) is a rare, sporadic histiocytic disorder characterized by painless but protracted lymphadenopathy. Its etiology remains unclear. The observation of congenital disease and reports of familial cases with seven pairs of siblings including three sets of identical twins suggests a genetic predisposition in some patients with this condition. We now report two brothers of consanguineous Palestinian parents, whose lymphadenopathy, lymph node histology, and polyclonal hypergammaglobulinemia indicated RDD. The presence of intrauterine fractures, short stature, and sensorineural hearing impairment suggested a rare familial form of the disorder. Moynihan et al. recently described a Pakistani family with a familial histiocytic disorder highly reminiscent of the brothers reported here, whose lymph node morphology was apparently consistent with RDD as well. The presence of sensorineural deafness, short stature, and joint contractures, however, suggested a separate, rare autosomal recessive syndrome referred to as Faisalabad histiocytosis, after the family's place of origin. We believe that the brothers described here represent a second family with Faisalabad histiocytosis, which mimics RDD histologically.     

Peripheral blood lymphocyte subpopulations in three infants with hepatosplenomegaly caused by cytomegalovirus infection

Mononucleosis is defined as atypical lymphocyte proliferation which causes clinical symptoms such as tonsillitis, lymphadenopathy, or hepatosplenomegaly. Mononucleosis syndrome is caused by cytomegalovirus (CMV), Toxoplasma, hepatitis virus, adenovirus, or other agents as well as by Epstein — Barr virus. The syndrome is immunologically characterized by the proliferation of activated T cells (HLA-DR⁺ T cells). We encountered three infants with hepatosplenomegaly who were diagnosed as primary CMV infection by the detection of anti-CMV IgM antibody. Although the patients were otherwise asymptomatic, analysis of lymphocyte subpopulations showed a decreased ratio of CD4⁺ to CD8⁺ T cells and augmented expression of HLA-DR antigen on T cells characteristic of infectious mononucleosis. We conclude that inapparent CMV disease may affect the immunologic status of infected children even if it is asymptomatic.     

Extranodal Rosai-Dorfman disease in children

Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease (RDD), is a histiocytic disorder that usually presents with painless massive cervical lymphadenopathy. The course is usually self-limited, but treatment may be required in cases with compression of vital organs. Patients may present with extranodal involvement only, and in these cases the clinical and histologic diagnosis may be difficult. The authors describe three patients with RDD who had exclusive extranodal disease in the head and neck area, in whom the clinical presentation mimicked other more common conditions.     

Erythroleukemia: a clinco-hematological review of four cases

Erythroleukemia is an uncommon disorder in children. Four cases of pediatric erythroleukemia, diagnosed over a period of nine years are presented. The patients presented with pallor, fever and hepatosplenomegaly of recent onset. Peripheral smear examination showed anemia, thrombocytopenia and circulating blasts. The bone marrow displayed erythroid hyperplasia with dysplasia and PAS positive erythroblasts. Myeloid blasts were myeloperoxidase positive and one case showed positivity for non specific esterase, indicating monocytoid differentiation, a poor prognostic feature. Prognosis was poor and follow up period was short.     

Systemic Form of Juvenile Xanthogranuloma: Report of a Case with Liver and Bone Marrow Involvement

Systemic form of juvenile xanthogranuloma with involvement of liver and bone marrow is reported in a 2-month-old female infant who presented with hepatosplenomegaly, severe anemia, and thrombocytopenia. There was no skin lesion, nor bone lesion. The enlarged liver has generalized yellowish spots. The diagnosis of juvenile xanthogranuloma was made by pathologic findings of marrow and portal tract infiltration by S-100 negative, CD1a negative, CD68 positive, and Factor XIIIa positive large pale to foamy histiocytes with Touton giant cells, and lack of Langerhans cell granule by electron microscopic examination. The patient was treated with Vinblastine and Etoposide, and experienced slow and gradual disease regression in one year. To the best of knowledge, this is the first documented case of bone marrow involvement in systemic juvenile xanthogranuloma. published online December 6, 2004     

Transaldolase deficiency: a new cause of hydrops fetalis and neonatal multi-organ disease

Transaldolase (TALDO) deficiency is a newly recognized metabolic disease, which has been reported so far in 2 patients presenting with liver failure and cirrhosis. We report a new sibship of 4 infants born to the same consanguineous parents; all presented at birth or in the antenatal period with dysmorphic features, cutis laxa and hypertrichosis, hepatomegaly, splenomegaly, liver failure, hemolytic anemia, thrombocytopenia, and genitourinary malformations. The clinical courses were variable: the first child died of liver failure at 4 months of age; the second pregnancy was medically terminated at 28 weeks gestation because of hydrops fetalis with oligohydramnios. The third child is doing well at age 7 with liver fibrosis and mild kidney failure. The fourth child is now 21 months old and has hepatosplenomegaly, mild anemia, and thrombocytopenia. Urine assessment of polyols showed elevations of erythritol, arabitol, and ribitol consistent with TALDO deficiency. TALDO activity was undetectable in the patients' tissues, and mutation in the TALDO1 gene was found in the 4 patients.     

Simultaneous Occurrence of Viral-Associated Hemophagocytic Syndrome and Langerhans Cell Histiocytosis: A Case Report

Langerhans cell histiocytosis (LCH) is a class I histiocytosis characterized by the presence of the pathologic Langerhans cell, an unique histiocyte. In contrast to LCH, class II histiocytosis is characterized by the proliferation of mononuclear phagocytes other than Langerhans cells and includes sinus histiocytosis with massive lymphadenopathy, viral-associated hemophagocytic syndrome, and familial hemophagocytic lymphohistiocylosis. Until now, these two classes have been considered separate, if related, entities. We report a 10-month-old girl who presented with pyrexia, hepatosplenomegaly, an edematous skin rash, anemia, thrombocytopenia, and a markedly elevated serum IgG and IgM antibody level to cytomegalovirus. Histologic proof of both hemophagocytosis in the liver and bone marrow and LCH in the skin was obtained at presentation. The clinical course and response to treatment over 6.5 years is recorded. Although the etiology of both class I and class II histiocytosis remains unknown, we speculate that the monocytic/macrophage disorder, as well as the LCH, were both triggered by virus or viral-related monokines secreted by activated macrophages.     

Generalized Lymphadenopathy in Infancy; a Case Report

Background

Rosai-Dorfman disease (RDD) is a rare disease of histiocytic cells, a cause of benign cervical lymphadenopathy (LAP) and massive generalized lymph node enlargement in children and adults. There are also some reports on involvement of other human body organs with or without LAP.

Case Presentation

A 7-month-old infant with chief complaint of generalized massive LAP was referred to our center. RDD was diagnosed according to clinical manifestations and confirmed through histopathologic and immunoreactivity study on the obtained sample by cervical lymph node biopsy.

Conclusion

RDD is not a malignant illness and lymph node enlargement most often decreases in its size happens without special treatment.