PEDIATRICS Vol. 114 No. 4 October 2004, pp. 1127 (doi:10.1542/peds.2004-1271)
Macrophage Activation Syndrome Mimicking Life-Threatening Infection in a Patient With Variable Immunodeficiency, Centromeric Instability, and Facial Anomalies
Nicolas André, MD, PhDDépartement Multidisciplinaire de Pédiatrie and Oncologie Pédiatrique
Hôpital Pour Enfants de "La Timone"
Marseille 13005, France
Bertrand Roquelaure, MD
Mathilde Caillez, MD
Département Multidisciplinaire de Pédiatrie
Hôpital Pour Enfants de "La Timone"
Marseille 13005, France
Marianne Chrestian, MD
Service d'Anatomie Pathologique et de Neuropathologie,
Hôpital de la Timone,
Marseille 13005, France
Anne Moncla, MD, PhD
Centre de Génétique Médicale
Hôpital Pour Enfants de "La Timone"
Marseille 13288, France
Carla Blanco-Betancourt, PhD
Claudine Schiff, PhD
Centre d'Immunologie de Marseille-Luminy
Marseille 13288, France
To the Editor.—
ICF syndrome is a rare autosomal recessive disease characterized by variable immunodeficiency, centromeric instability, and facial anomalies.1,2 In most ICF cases reported, mutations in the DNA methyltransferase 3B gene are implicated.1,2 Negative selection breakdown and peripheral B cell maturation blockage contribute to agammaglobulinemia in ICF syndrome.3 The consequences of immunodepression are a higher frequency of infections such as recurrent and prolonged respiratory infections and infections of the skin and digestive system, which can be frequently lethal, leading to premature death of affected patients.4
Macrophage activation syndrome (MAS) is a serious complication of childhood systemic inflammatory disorders that is caused by excessive activation and proliferation of T lymphocytes and macrophages.5 Although the clinical and biological diagnosis criteria of MAS are well established,6 early diagnosis remains difficult.
We report the case of a young girl with ICF syndrome who presented with MAS mimicking life-threatening septicemia who responded well to corticoids.
S.A. is a young girl in whom the diagnosis of ICF syndrome was made at the age of 2 years. She presented with recurrent infections, facial anomalies, and cytogenetic abnormalities. No DNA methyltransferase 3B mutations were found in this patient (patient 4 in ref 3).
At 5 years old, she presented with a high-grade fever, hepatomegaly, and diffuse edema. Her infectious disease work-up was negative. Because of her medical history, antibiotherapy with teicoplanin, imipenem, and amphotericin B was initiated. Over 20 days, she developed cardiovascular collapse and respiratory distress and was transferred into the pediatric intensive care unit of our hospital. Broad-spectrum antibiotherapy and systemic antifungal therapy were maintained. Cardiovascular support and artificial ventilation were started, but the situation became critical. MAS was suspected because of the association of fever, hepatosplenomegaly, and pancytopenia (platelet count: 115.109 per L; hemoglobin: 73 g/L [hemoglobinemia]; white blood cell count: 3.8 x 109 per L). Additional laboratory studies showed hypertriglyceridemia (triglycerides: 3.5 mmol/L) and hypofibrinogenemia (fibrinogen: 1.5 g/L), a lactate dehydrogenase level of 1800 IU/L, and a C-reactive protein level of 222 mg/mL). Testing on bone marrow aspirates were performed, and typical hemophagocytosis was found. Therefore, based on the guidelines from the FHL Study Group of the Histiocyte Society,6 the diagnosis of MAS was made. Corticotherapy was initiated at the dose of 10 mg/kg per day, and evolution was favorable within 3 days. She left the intensive care unit after 3 days and was discharged from the hospital after 2 weeks. Six months later, she did not show any relapse.
MAS bears close resemblance to secondary hemophagocytic lymphohistiocytosis, which can be met in a diverse group of diseases including infections, neoplasms, hematologic conditions, and rheumatic or autoimmune disorders.7 Whether the association of MAS and ICF is fortuitous or MAS is a feature of the underlying syndrome remains to be confirmed by additional reports. Nevertheless, although this is the first case of MAS in children with ICF, it could represent an underestimated complication in children with this disease. Physicians should be alert that MAS is a potentially lethal complication among patients with ICF.
REFERENCES
- Xu GL, Bestor TH, Bourc'his D, et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature. 1999;402 :187 –191[CrossRef][Medline]
- Erlich M. ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency disease. Clin Immunol. 2003;109 :17 –28[CrossRef][Web of Science][Medline]
- Blanco-Betancourt CE, Moncla A, Milili M, et al. Defective B-cell-negative selection and terminal differentiation in the ICF syndrome.
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[Abstract/Free Full Text] - Haas OA. Centromeric heterochromatin instability of chromosomes 1, 9, and 16 in variable immunodeficiency syndrome—a virus-induced phenomenon? Hum Genet. 1990;85 :244 –246[Web of Science][Medline]
- Ramanan AV, Schneider R. Macrophage activation syndrome—what's in a name!
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[Free Full Text] - Henter JI, Elinder G, Ost A. Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society. Semin Oncol. 1991;18 :29 –33[Web of Science][Medline]
- Athreya BH. Is macrophage activation syndrome a new entity? Clin Exp Rheumatol. 2002;20 :121 –123[Web of Science][Medline]
PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics
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