eMedicine Specialties > Emergency Medicine > Rheumatology

Sarcoidosis

Author: Ramy Yakobi, MD, MBA, Medical Director of Emergency Department, Beth Israel/Kings Highway Division; Lecturer, Physician Assistant School, Cornell School of Medicine; Lecturer, Pre-hospital Management of Patient, Cornell/New York Presbyterian Hospital; Director of Emergency Department, New York Community Hospital
Contributor Information and Disclosures

Updated: Jul 28, 2009

Introduction

Background

Since 1865-75, when Sir Jonathan Hutchinson first described the disease that today is believed to be sarcoidosis, attempts to determine its primary etiology have failed. Sarcoidosis is a chronic noncaseating granulomatous disease of unknown etiology that affects many organs and tissues, most commonly the lungs.

Although sarcoidosis may be suspected by a patient's history, it usually is diagnosed by using chest radiography and histology. Emergency medicine physicians may diagnose this disease de novo or treat its exacerbations, recurrences, and/or complications.

Pathophysiology

The basic pathological finding in sarcoidosis is a noncaseating granuloma that is formed in response to an exaggerated immune reaction mediated by T-helper cells. The etiology is unknown, although increased immunoglobulin M (IgM) and hyperglobulinemia against various infectious agents are present.

Granulomas also share characteristics of infectious and noninfectious (eg, inhaled agents) etiologies. Cutaneous anergy, lymphopenia, and inversion of the CD4/CD8 ratio in the blood suggest the involvement of T-helper cells. The T-helper cells, together with other inflammatory cells (eg, macrophages, B cells), compose the granuloma.

Within the basic structure, centrally located multinucleated giant cells contain Schaumann bodies (ie, calcifications) and asteroid bodies. In addition to multinucleated cells, granulomas also contain monocytes, lymphocytes, fibroblasts, and macrophages, which confirms the exaggerated immune response of unknown etiology. The macrophages release interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF), 1,25-dihydroxyvitamin D, and angiotensin-converting enzyme.

If the inflammatory reaction is prolonged, fibroblast proliferation mediated by IL-1, IL-6, and TNF occurs with consequent fibrosis of healthy tissue. Fibroblast proliferation occurs in about 20% of patients.

No evidence indicates that the inflammatory cells release chemical mediators to affect the function of the involved organ. Rather, the organ involved is believed to manifest its symptoms because of the volume occupied by granulomas.

Granulomas can decrease in number if sarcoidosis is contained spontaneously or if it responds to treatment.

Frequency

United States

The overall prevalence of sarcoidosis is 10-40 cases per 100,000 population.

Although initially thought to be more prevalent in the southeastern United States, recent studies find this statistic to be inaccurate. The disease is 3-4 times more prevalent among the African American population.

International

The overall prevalence of sarcoidosis is similar to that in the United States. Sweden is most affected, with 64 cases per 100,000 population. Incidence in Poland is rare, with 3 cases per 100,000 population. Sarcoidosis is almost unknown among persons of Native Indian, Australian Aboriginal, or southern Asian (eg, Korean) descent.

Mortality/Morbidity

The disease can present as acute, subacute, or chronic.

• Most patients who present with acute disease are left with minimal or no symptoms, even if damage to the affected organ, although clinically silent, is permanent.
• Approximately 15-20% of patients have intermittent recurrences, and fatality occurs in 10% of patients because of extensive organ involvement.
• No conclusive studies have confirmed whether smoking worsens the course or the outcome of sarcoidosis. In some studies, it was observed that smoking had a protective role on incidence and outcome because cigarette smoking reduced IL-6 levels and the consequent immune response. Other studies concluded that airflow obstruction was more frequent among smokers than nonsmokers.¹

Race

While the sarcoidosis affects all races, in the United States, incidence among black persons is 3-4 times higher than among the white population. A recent theory has advanced that African Americans with HLA-DR 11, 12, 14, 15, and 17 are more prone to develop sarcoidosis while HLA DRI, DR4 seem to have protective effect.

Sex

Females are affected more often than males.

Age

Although 20- to 40-year-old individuals are most commonly affected (70-90% of cases are in this age group), sarcoidosis is also known to occur in persons aged at the extremes of life. Geographic and environmental factors may explain differences in age of onset. It may be familial and can affect twins.

Clinical

History

In the ED, a patient may present with nonspecific complaints or be diagnosed incidentally by radiograph and/or other findings. Approximately 50% of patients are asymptomatic at diagnosis. Patients may present to the ED with a known diagnosis of sarcoidosis and complain of symptoms consistent with a recurrence. Because sarcoidosis is a multiorgan disease, patients may complain of a variety of symptoms that may complicate diagnosis.

• The organs most affected are as follows:
  • Lungs (90% with abnormal chest radiographic findings at some point)
  • Lymphatics (75% of pulmonary and 60% of peripheral)
  • Skin (25%)
  • Eyes (25%)
  • Bone marrow (30%)
  • Liver (60-90%)
  • Spleen (40%)
  • Upper respiratory tract (nose, tonsils in 20%)
  • Salivary glands (parotitis)
  • Musculoskeletal (acute or chronic arthritis; see Lofgren syndrome below)
  • Kidney (mainly as a kidney stone secondary to hypercalcemia; hypercalcemia is produced by calcitriol hyperactivity of macrophages)
  • Central nervous system (5%)
  • Joint (25%)
  • Heart (5%) (can present as a conduction defect; also, in advanced cases, pulmonary hypertension causes cor pulmonale)
  • Endocrine system
  • Gastrointestinal system
• Patients may present with the following:
  • No symptoms; diagnosed incidentally because of chest radiographic findings
  • Abrupt onset of signs and symptoms evolving over 1-3 weeks; occurs in 40% of cases and consists of constitutional complaints and/or other findings (see below)
  • Chronic onset that evolves over a few months and is observed in 60% of patients; respiratory signs and symptoms predominate (see below)
  • Recurrences
• Constitutional symptoms
  • Fever/night sweats
  • Malaise
  • Fatigue
  • Weight loss
  • Arthritis, uveitis, cranial nerve VII involvement, and parotid enlargement (ie, Heerfordt-Waldenström syndrome)
• Pulmonary: Approximately 90% of patients have an abnormal radiographic finding at some stage of the disease; 10% have pulmonary fibrosis.
  • Dry cough
  • Dyspnea that worsens upon or with exertion
  • Occasional hemoptysis
  • Pleural effusion and pneumothorax (rare)
• Lymph nodes: These are found in hilar and peripheral locations, such as cervical, axillary, and inguinal.
• Skin
  • Maculopapular eruptions, involving the nares, lips, eyelids, and previous trauma areas
  • Lupus pernio (specific for sarcoidosis), a plaquelike lesion of violaceous discoloration of the nose, cheeks, chin, and ears
  • Erythema nodosum (EN), the most common skin manifestation, referred to as Lofgren syndrome when it occurs with radiographic findings of bilateral hilar or paratracheal adenopathy and joint involvement (EN is associated with a good prognosis.)
  • Subcutaneous nodules
• Ocular lesions can manifest with the following:
  • Uveitis
  • Retinal vasculitis
  • Keratoconjuctivitis
• Neurologic: Given such a range of neurologic involvement, patients may present with virtually any neurologic complaint.
  • Facial numbness and dysphagia
  • Hoarseness
  • Decreased gag reflex
  • Headache
  • Visual deficit
  • Polydipsia
  • Deafness
  • Involvement of cranial nerves VII, VIII, IX, and X
  • Basal granulomatous meningitis with involvement of optic chiasm and optic nerve
  • Signs of meningitis (aseptic meningitis that, on CSF examination, shows decreased glucose, increased protein, increased lymphocytes)
  • Involvement of the hypothalamic-pituitary axis (manifests with pituitary insufficiency, optic chiasm compression, DI)
  • Seizures
  • Vasculitis
  • Stroke or transient ischemic attack
  • Peripheral neuropathy (possibly manifesting with paresthesias and decreased deep tendon reflexes [DTRs])

Physical

• Skin
  • Maculopapular eruptions (see Skin above)
  • Lupus pernio (violaceous lesions on the face and/or extremities)
  • Erythema nodosum (red painful lesion on the extensor surface of the lower extremities); considered to be the most common skin lesion in sarcoidosis
  • Granuloma formation in old scar or tattoo and subcutaneous nodules
• Cranial nerve VII involvement (unilaterally or bilaterally), Bell palsy, basal granulomatous meningitis (ie, aseptic meningitis), or peripheral neuropathies; each presenting with the proper constellation of symptoms
• Ocular: The number of patients who were later diagnosed with sarcoidosis initially presented with ophthalmologic or neuro-ophthalmologic findings before the systemic manifestations.
  • Uveitis presents with blurry vision, tearing, and photophobia.
  • Conjunctiva may present with infiltration that has the appearance of a yellowish nodule.
  • Keratitis sicca presents with complaints of dry eyes.
• Musculoskeletal
  • Myositis
  • Polyarthritis: Spondyloarthropathy, for example, has a higher incidence and prevalence in patients with sarcoidosis (6.6%) than in the general population (1.9%). An association with positive HLA-B27 was evident, suggesting an association between sarcoidosis and spondyloarthropathy. Thus, a patient with sarcoidosis may present with back pain or sacroiliac pain. Note that Lofgren syndrome includes arthritis.
  • Bony lesions
• Head, neck, and upper respiratory tract
  • Dry cough
  • Rales
  • Tonsillitis, parotitis (Heerfordt syndrome), and epiglottitis that presents as hoarseness, stridor, or cough
  • Nasal involvement (may present as damage to septum and turbinates)
• Cardiac
  • Cor pulmonale (most common cardiac complication); caused by pulmonary fibrosis
  • Complete heart block, ventricular tachycardia (most common arrhythmia), bundle-branch block (BBB), ventricular aneurysm, myocarditis, pericarditis, and congestive heart failure (CHF)
• Painless nonadherent lymph nodes
• Splenomegaly (occurs in 10% of cases); presents with hematologic and general complications (eg, rupture)
• Hepatomegaly (occurs in 25% of cases, with elevation in LFTs); usually not clinically significant
• Nephrolithiasis; may be caused by hypercalcemia and hypercalciuria secondary to increase in 1,25-dihydroxyvitamin D and calcitriol production by activated macrophages
• Clinically significant renal failure (uncommon)

Causes

The exact cause of sarcoidosis is unknown, but immune mechanisms are essential to the etiology.

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