Akram Pourshams MD, Assistant Professor, Mohammad Yaghoobi MD, Research Fellow, Ahmad–Reza Soroush MD, Associate Professor, Bahram Mohebbi MD, Resident of Internal Medicine, Masoud Sotoudeh MD, Associate Professor, Rasoul Sotoudemanesh MD, Assistant Professor, Digestive Disease Research Center, Tehran University of Medical Sciences.

The patient symptoms deteriorated with time. Palatal ulceration and muscle weakness added to the clinical picture, and she sought medical attention 1 month later because of continuous fever, jaundice, hepatosplenomegaly and mid-palate necrotic ulcer, and was referred to another hospital.

Table 1. The patient’s characteristics at first admission.

At the time of her referral to Shariati Hospital, she was conscious and neurologic, cardiovascular and pulmonary examinations were normal. There was no evidence of ascites or peripheral lymphadenopathy. Table 2 presents the laboratory findings after her second admission.

Pathologic examination showed acute necrotizing inflammation in the palatal lesion, a megaloid reaction and mild reactive lympho-plasmocytosis in bone marrow aspiration, and extensive steatohepatitis with a large bile duct obstruction.

Because the initial diagnostic evaluation methods did not lead to a definite diagnosis, she underwent diagnostic laparotomy. During laparotomy, a splenectomy was performed and biopsies were taken from the liver and mesenteric lymph nodes.

Table 2. The patient’s characteristics at second admission.

Your Diagnosis?

The pathologist reported the following:

1- In the spleen: Malignant lymphoma with erythrophagocytic syndrome (Figure).

2- In the lymph node: Hyperplasia and reactive lymph node with atypical sinus histocytosis.

3- In the liver: Cholangiohepatitis with marked fatty changes and focal hemorrhage.

Hemophagocytic syndrome (HPS) is a rare fulminant disease characterized by generalized histiocytic proliferation associated with phagocytosis of erythrocytes, platelets and, to a lesser extent, white blood cells.^1,2

To our knowledge, there have been no reports of this condition in Iran. HPS has been reported as a condition associated with certain diseases, but not as an independent entity. Review of the literature suggests that HPS is a very rare disease in Western countries, but is more common in Southeast Asia. It is reported that children and young adults are involved more frequently than older people.^3–5 The majority of reported cases, including ours, are female, but no sex predominance was mentioned in published series.^3,4 High numbers of female case reports may suggest autoimmunity as a contributory factor in the etiology of HPS.

Clinical, laboratory and histopathologic features of HPS are shown in Table 3.⁷ Fever and splenomegaly are the most frequent clinical signs, and hepatomegaly, lymphadenopathy, jaundice and rash are less common findings.⁸ Encephalopathy, meningismus, and seizures are the most frequent neurologic manifestations.^9,10 These clinical findings may suggest an acute viral infection, such as infection with Epstein-Barr virus (EBV) or cytomegalovirus (CMV), viral hepatitis, or acute HIV seroconversion. When these conditions actually coexist with HPS, the situation is more complicated.

Among laboratory abnormalities, cytopenia is the most frequent and may be profound. Serum chemistry profile may suggest hemolysis, with hyperbilirubinemia and elevation of lactate dehydrogenase (LDH) as well as hypertriglyceridemia and marked elevation of ferritin.^11,12 Serum fibrinogen is typically low if disseminated intravascular coagulation has occurred.¹³ Increases in circulating fibrin degradation products and serum ferritin are reported to be associated with an elevated risk of death in patients with HPS.¹⁴

Table 3. Clinical and laboratory abnormalities associated with HPS

Hemophagocytosis can be found in bone marrow, spleen and lymph nodes,^15,16 and less frequently in the central nervous system^9,17 and skin⁸. Activated macrophages are able to ingest erythrocytes, leukocytes and platelets, their precursors, and cellular fragments. Hemophagocytosis may be present in the liver, and infiltration of the hepatic portal tracts with lymphocytes is also common.^15,16

Rare occurrence of HPS, especially in Western countries may explain the lack of sufficient knowledge about this condition.