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CHaPter 73 Sarcoidosis 987

changes without erosive chondritis. Cystic lesions of the long female sex, lower socioeconomic status, poor access to care, and
bones, pelvis, sternum, skull, and vertebrae are rare. increased disease severity, but not with race.
Neurosarcoidosis
Neurosarcoidosis occurs in 5–15% of patients with sarcoidosis. KeY COnCePts
The most common manifestation is cranial neuropathy, most Clinical Relevance
frequently bilateral or unilateral seventh-nerve (facial) palsy. The
palsy may resolve spontaneously or with corticosteroids but • Multisystem disease with heterogeneous manifestations and clinical
sometimes recurs years later. Optic neuritis may result in blind- course
ness. Manifestations of central nervous system (CNS) involvement • Diagnosis based on consistent manifestations and biopsy showing
include mass lesions, aseptic meningitis, obstructive hydrocepha- typical pathology
• No useful biomarkers for diagnosis or prognosis
lus, and hypothalamic/pituitary dysfunction. Seizures, headache, • Differential includes infections (mycobacterial, fungal), malignancy
change in mental status, confusion, and diabetes insipidus may (e.g., lymphoma), immunoglobulin G4 (IgG4)–related disease;
be presenting symptoms. Myelopathy with paraparesis, hemi- interstitial lung diseases
paresis, and back and leg pain have been described. Peripheral • Association with T-helper 1 (Th1) –promoting therapies
neuropathies account for ≈15% of cases of neurosarcoidosis, • After treatment with interferon (IFN)-α, IFN-γ, and interleukin (IL)-2
and other biologicals
often presenting as mononeuritis multiplex or a primary sensory • After immune reconstitution in patients with human immunodefi-
neuropathy. Small-fiber neuropathies with or without autonomic ciency virus (HIV) infection undergoing highly active retroviral therapy
neuropathy are increasingly recognized in patients with sarcoid- (HAART)
osis, particularly those with pain and chronic disease. • Goal of treatment with immunosuppressive medications is to preserve
function of affected organs while improving quality of life
Salivary, Parotid, and Lacrimal Gland Sarcoidosis • Clinical trials needed to establish roles of individual therapies
• Benefit of anti–tumor necrosis factor (TNF) therapies point to a role
Parotid or lacrimal gland enlargement and sicca syndrome may
be the dominant clinical manifestations of sarcoidosis. Heerfordt for TNF in sarcoidosis
syndrome, also known as uveoparotid fever, manifests as fever,
parotid and lacrimal gland enlargement, uveitis, and bilateral
hilar adenopathy, sometimes with cranial neuropathies (usually Associated Conditions
facial palsy). Sarcoidosis and Pregnancy
Pregnancy usually has little effect on the course of sarcoidosis,
Hematological Sarcoidosis although some patients experience spontaneous improvement.
Peripheral lymph node enlargement occurs in 20–30% patients In those whose condition improves during pregnancy, exacerba-
as an early manifestation of sarcoidosis but then typically remits tions frequently follow several months after delivery. The tem-
spontaneously. Persistent, bulky lymphadenopathy occurs in porary clinical improvement may relate to suppressed Th1
<10% of patients. Splenomegaly occurs in <5% of cases. It is immunity during pregnancy.
occasionally massive and often associated with hepatomegaly or
hypercalcemia. Polyclonal hypergammaglobulinemia is present Th1-Promoting Therapeutics
in ≥25% of patients. Administration of Th1-promoting therapeutics, such as IFN-α,
IFN-γ, IL-2, and IFN-β, has been linked to initiation or recru-
Sarcoidosis Myopathy descence of sarcoidosis.
Although random muscle biopsy specimens at autopsy have
demonstrated muscle granulomas in most patients with sarcoid- Common Variable Immunodeficiency
osis, symptomatic myopathy with weakness and tenderness is Sarcoidosis is associated with common variable immunodeficiency
uncommon. Rarely, sarcoidosis can present as a polymyositis (CVID) in both adults and children. A high index of suspicion
with profound weakness and elevated serum creatine kinase and must be maintained for this in patients with sarcoidosis who
aldolase. have recurrent infections.
Hypercalcemia, Hypercalciuria, and Renal Disease IgG4-Related Disease
Hypercalcemia is present in 2–5% of patients; hypercalciuria is This lymphoproliferative disorder involves multiple organ systems
more common. Abnormal calcium regulation may cause kidney and can be mistaken for sarcoidosis, particularly when central
stones or nephrocalcinosis and is thought to result from enhanced or peripheral adenopathy are present. Distinguishing features
conversion of 25-OH vitamin D 3 to the active 1,25-(OH) 2 vitamin of IgG4-related disease include the presence of dense lympho-
D 3 by macrophages and epithelioid cells in granulomas expressing plasmacytic infiltrates on biopsy, autoimmune pancreatitis and
1α-hydroxylase (also known as cytochrome p450 27B1). Impor- other autoimmune phenomena, and the presence of fibrosis in
tantly, if patients with sarcoidosis are screened for vitamin D organs not commonly involved in sarcoidosis, such as the
deficiency, they may have low 25-OH vitamin D 3 levels and peritoneum, aorta, and thyroid gland.
elevated active 1,25-(OH) 2 vitamin D 3 levels, placing them at
risk of nephrocalcinosis with renal failure if they are given vitamin Human Immunodeficiency Virus
D supplements. Sarcoidosis may develop in patients infected by human immu-
nodeficiency virus (HIV) with immune reconstitution after
Psychosocial Manifestations starting antiretroviral therapy, perhaps from reconstituted Th1
Depression and/or fatigue have been found in 30–60% patients immunity. Granulomatous inflammation of skin or lungs is most
with symptomatic sarcoidosis. Depression is associated with often reported.