Page 876 - Clinical Immunology_ Principles and Practice ( PDFDrive )

848 Part Seven Organ-Specific Inflammatory Disease

Therapy
TABLE 62.2 Causes of Immune
The first line of therapy is corticosteroids, and 80% of patients neutropenia
achieve a partial or complete response to 1 mg/kg/day of pred-
nisone (orally). Once a response is achieved, the prednisone Primary
dose is tapered slowly. Approximately 50% of patients require Isoimmune neonatal neutropenia
prednisone at a dose of 15 mg/day or less to maintain the Autoimmune neutropenia of childhood
Adult autoimmune neutropenia
hemoglobin level >10 g/dL, and it may take up to 3 weeks for
patients to achieve a response. Patients who do not respond in Secondary
3 weeks should be started on second-line therapy. It is estimated Systemic autoimmune disease
that long-term complete responses not requiring prednisone Rheumatoid arthritis (i.e., Felty syndrome)
can be achieved in 20% of patients. 15 Systemic lupus erythematosus
Sjögren syndrome
tHeraPeUtIC PrInCIPLeS Lymphoproliferative malignancy
Autoimmune Anemia Large granular lymphocyte (LGL) leukemia
Lymphoma
• Hemolytic anemia induced by “warm” antibody Drug-Induced
• Acute: corticosteroids, transfusion if severe
• Chronic: splenectomy, rituximab, immunosuppression Antiplatelets—ticlopidine
• Hemolytic anemia induced by “cold” antibody Inflammatory bowel disease drug—sulfasalazine
• Cold agglutinin disease: avoidance of cold; rituximab +/− fludarabine Antipsychotic—clozapine, phenothiazines
• Paroxysmal cold hemoglobinuria: avoidance of cold; corticosteroids Antithyroid medications—propylthiouracil, methimazole
• Hemolytic disease of the newborn Retrovirals
• Neonatal exposure to fluorescent light Antibiotics—beta-lactams, cefepime, trimethoprim-sulfamethoxazole,
• Intrauterine transfusion or exchange transfusion vancomycin, rifampicin, quinine/quinidine
Diuretics—furosemide, spironolactone
Antiepileptic—lamotrigine
Splenectomy and anti-CD20 antibody (rituximab) are Rituximab, infliximab, etanercept
considered second-line therapy. Splenectomy is associated with
short-term partial or complete responses in two-thirds of patients.
The overall response rate to rituximab is approximately 80%, but antibodies usually disappear within 12–15 weeks, but occasionally
rituximab is contraindicated in patients with untreated hepatitis it can persist as long as 24 weeks after delivery.
B. The rare, but most severe, long-term complication of rituximab
therapy is progressive multifocal leukoencephalopathy. 15 Primary Autoimmune Neutropenia
Danazol, a synthetic anabolic steroid, has been used as a Primary autoimmune neutropenia is an antibody-mediated
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first-line agent in conjunction with prednisone; its effectiveness disease that presents commonly in early childhood. Patients
appears to be less in relapsed or refractory disease. The role of typically have normal blood counts at birth and develop neu-
high-dose intravenous immunoglobulin (IVIG) remains con- tropenia at 3–36 months of age. Children presenting at <2 years
troversial; its effectiveness remains to be determined in larger of age most commonly recover spontaneously within 2–3 years
trials. Third-line therapy consists of immunosuppressive agents of diagnosis. Nevertheless, some children, particularly those
(e.g., azathioprine, cyclophosphamide, alemtuzumab, mycophe- presenting at older ages or manifesting other autoimmune
nolate mofetil, cyclosporine). 1,15 findings, develop a chronic neutropenia disorder. Primary immune
neutropenia (in the absence of other disease manifestations) is
IMMUNE-MEDIATED NEUTROPENIA less common in adults. Rigorous incidence data are lacking, but
a small retrospective study in Sheboygan County, Wisconsin,
Immune neutropenia constitutes a heterogeneous group of found an annual incidence of 5–10 cases of primary or secondary
acquired diseases in which the immune system responds to neutropenia per 100 000 people.
circulating neutrophils, selectively reducing their level to below
3
1500 cells/mm (Table 62.2). Neutropenia Associated With Systemic Autoimmune or
Lymphoproliferative Diseases
KeY COnCePtS Most patients with active systemic lupus erythematosus (SLE)
Immune Neutropenia develop neutropenia as part of a more global leukopenia (Chapter
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51). Separately, a smaller subset develops severe neutropenia,
• Immune neutropenia in children is caused by antineutrophil antibodies presumably mediated by ANAs. Sjögren syndrome (Chapter 54)
(ANAs). and other systemic autoimmune diseases are also sometimes
• Immune neutropenia in adults has a more complex etiology. complicated by immune neutropenia. Lymphoproliferative
• Immune complex-mediated neutrophil clearance and cell-mediated disorders, such as chronic lymphocytic leukemia (Chapter 78),
suppression of myelopoiesis often play a major role.
can occasionally be complicated by immune neutropenia as well.
Isoimmune Neonatal Neutropenia Felty Syndrome
Transient neutropenia analogous to neonatal immune hemolysis Immune neutropenia develops in about 1% of patients with
or thrombocytopenia develops when IgG antineutrophil antibod- rheumatoid arthritis, most commonly (but not exclusively) in
ies (ANAs) from an allosensitized or autoimmune mother cross association with splenomegaly, a combination designated as Felty
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the placenta and destroy fetal neutrophils. Neutropenia is syndrome. Patients typically express human leukocyte antigen–
typically present at birth and resolves spontaneously, as maternal DR4 (HLA-DR4) and have long-standing seropositive rheumatoid