X-linked familial hemophagocytic lymphohistiocytosis; XIAP deficiency; X-linked lymphoproliferative syndrome type 2 (XLP-2)-MAS

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SAID group:
Macrophage Activation Diseases


X-linked. X-linked dominant male inheritance (typical presentation). There are some female carriers with some symptoms. Testing recommended for XIAP (and also SAP) in males with symptoms of HLH after Epstein-Barr virus (EBV) infections, or HLH presenting in childhood or adolescence. [84]



Timing of symptoms:
Onset of HLH may be the first sign of this disease, and may occur after Epstein-Barr infections (that can be severe). [85] Some cases developed pancytopenia and splenomegaly after MMR vaccine. [88]

Age of onset:
Infancy to early childhood. A few with school-age onset. [84] [88]

Skin cutaneous:
Some patients may have erythema nodosum, including female carriers of an XIAP deficiency. [85] One case of recurrent rashes with fevers. [83]

Prolonged, periodic fevers >7 days. [84] A few with pathologic cerebrospinal fluid (CSF). [85]

Uncommon. One case with sensorineural hearing loss in childhood. [83] Hearing loss not noted in other cases. [84] [85]

Uveitis [83] [87]. One case with bilateral cataracts in early childhood. [83]

Severe cases of infectious mononulcleosis leading to HLH is common. [84] [85] Some with increased risk for severe, recurrent or rare respiratory infections. [88]

Higher risk for early-onset inflammatory bowel diseases (Crohns, colitis, IBD), even in female carriers of the XIAP deficiency mutation. [85] Hepatomegaly, splenomegaly, granulomatous hepatitis. [83] [88] Chronic and/or hemorrhagic colitis that can be fatal (one case with portal hypertension). [88] Crohns-like disease, celiac-like disease. [87] Some patients with chronic liver failure and/or hepatitis. [85] Cholangitis (sometimes associated with colitis). [88]

Splenomegaly (may be the first presenting symptom). [88] Hemophagocytic lymphohistiocytosis (HLH) affects 90% of cases [85] and many can have recurrent HLH. HLH can occur after Epstein-Barr virus (EBV). [85] [88] No known patients with lymphoma or aplastic anemia. [84]

Joints bones muscles cartilage:
Uncommon. [84] [85] [88] One case with arthritis in the hips and knees that also developed myositis. [83]

Not noted. [83] [84] [88]

One case with elevated serum amyloid. [83] Not tested in other cases in the literature.

Abnormal labs:
High: ESR, CRP, liver function tests (LFTs), triglycerides, ferritin, [85] IL-18 [86] cytopenia. [85] Low: fibrinogen, platelets, anemia, neutropenia, hemophagocytosis. [88] Normal NK cell function [85] Variable NKT cell defects. [84] IgG normal in untreated patients. [85] Low IgG secondary to treatments. [84] [85]

Search Keywords:
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