ALTERNATE NAMES

Erythrophagocytic Lymphohistiocytosis; Familial Erythrophagocytic Lymphohistiocytosis; Familial Hemophagocytic Lymphohistiocytosis; Familial Histiocytic Retulosis; FHL; FHLH Types 1, 2, 3, 4, and 5; HLH; HPLH

DESCRIPTION

Hemophagocytic lymphohistiocytosis - familial type (FHLH) is a rare, genetic disease that is caused by mutations in the perforin 1 (PRF1) gene. FHLH is characterized by uncontrolled activation of the immune system. The T cells, macrophages, and overproduced inflammatory cytokines infiltrate the liver, spleen, bone marrow, and central nervous system resulting in a multi-system disorder. The highly stimulated and ineffective immune response threatens the life of the individual and may lead to death unless appropriate and timely treatment is provided. The condition commonly appears in infants and during early childhood, although it can appear in all age groups. FHLH can be triggered by infections, viruses such as Epstein-Barr, rheumatic diseases, and malignancies.

DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM/ICD-10-CM CODING

Diagnostic testing: A molecular diagnosis confirms the disease. Clinical evaluation of fever and splenomegaly (enlarged spleen), and blood tests which measure high triglycerides, ferritin, transaminases, bilirubin, coagulation time, and decreased fibrinogen.

Physical findings: Children with FHLH present with:

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  Prolonged high fever;

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  Splenomegaly;

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  Liver abnormalities;

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  Cytopenia (low blood cell or platelate levels);

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  Hypofibrinogenemia (low or unmeasurable plasma fibrinogen antigen levels) or hypertriglyceridemia (high level of triglycerides in the blood);

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  Hematophagocytosis (engulfment and destruction of blood cells in the bone marrow and other tissues);

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  Skin rashes on the scalp and behind the ears;

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  Swollen or hemorrhagic gums;

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  Abdominal pain;

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  Vomiting;

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  Diarrhea;

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  Weight loss;

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  Jaundice (yellowing of skin or whites of the eyes); and

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  Failure to thrive.

ICD-9: 288.4

ICD-10: D76.1

PROGRESSION

FHLH is uniformly fatal if not treated. The prognosis is varied for those receiving treatment. The median survival time is two to six months after diagnosis without treatment, but survival time has dramatically improved with advent of recent treatment protocols.

Even with treatment, approximately 21% of individuals with FHLH can be expected to survive five years but survival rates of up to 66% have been reported in those receiving bone marrow transplantation (versus 10% of patients receiving chemotherapy alone). Success or failure of an allogenic bone marrow transplant is the most important long-term prognostic factor. Without treatment, the uncontrolled inflammatory response leads to sustained neutropenia and death from bacterial or fungal infections as well as from cerebral dysfunction.

TREATMENT

Individuals with FHLH may be classified into high-risk and low-risk groups. Patients who are at low risk may be treated effectively with cyclosporine, corticosteroids, or intravenous immunoglobulin (IVIG). Those at high-risk may require chemotherapy. The first goal of treatment is to achieve clinical stability and then to cure with bone marrow transplant.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

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  Clinical history and examination that describes the diagnostic features of the impairment; and

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  Laboratory studies measuring high triglycerides, ferritin, transaminases, bilirubin, coagulation time, and decreased fibrinogen.

Suggested Listings for Evaluation:

DETERMINATION

LISTING

REMARKS

Meets

Equals

114.06

114.07 A or B

Need to differentiate FHLH from acquired or secondary HLH, which has a very good prognosis.