AUTHOR INFORMATION

Section 1 of 12

Authored by Ramy Yakobi, MD, MBA, Assistant Professor of Emergency Medicine, Adjunct Lecturer at Physician Assistant School, Cornell Weill Medical School; Consulting Staff, Department of Emergency Medicine, New York Presbyterian Hospital

Coauthored by David Cheng, MD, Assistant Professor, Department of Surgery, Division of Emergency Medicine, New York Presbyterian Hospital, Cornell University

Ramy Yakobi, MD, MBA, is a member of the following medical societies: Society for Academic Emergency Medicine

Edited by Joseph A Salomone III, MD, Associate Professor, Department of Emergency Medicine, Truman Medical Center, University of Missouri at Kansas City School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Gino A Farina, MD, Program Director, Associate Professor of Clinical Emergency Medicine, Department of Emergency Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Robert E O'Connor, MD, MPH, Director of Education and Research, Department of Emergency Medicine, Christiana Care Health System; Professor of Emergency Medicine, Thomas Jefferson University

Author's Email:	Ramy Yakobi, MD, MBA
Editor's Email:	Joseph A Salomone III, MD

eMedicine Journal, February 7 2005, VOLUME 6, Number 2

INTRODUCTION

Section 2 of 12

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.

While sarcoidosis may be suspected by a patient's history, it usually is diagnosed by chest x-ray 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. The macrophages release IL-1, 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, it is believed that the organ involved manifests 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:

• In the US: 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.

• Internationally: The overall prevalence of sarcoidosis is similar to 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 and the consequent immune response. Other studies concluded that airflow obstruction was more frequent among smokers than nonsmokers.

Race: While the disease affects all races, in the United States, incidence among black persons is higher than among white persons, with a ratio of 10-20:1. A recent theory has advanced that black persons with HLA-Bw15 are more prone to develop sarcoidosis than white persons, but this conclusion requires further investigation.

Sex: Females are affected more often than males.

Age: Although 20- to 40-year-old individuals are most commonly affected, 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

Section 3 of 12

History: In the ED, a patient may present with nonspecific complaints or be diagnosed incidentally by x-ray 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 x-ray 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)

  • Kidney (mainly as a kidney stone)

  • Central nervous system (5%)

  • Joint (25%)

  • Heart (5%)

  • Endocrine system

  • Gastrointestinal system

• Patients may present with the following:
  • No symptoms; diagnosed incidentally because of chest radiograph 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-Waldenstrom syndrome)

• Pulmonary: Approximately 90% have an abnormal x-ray finding at some stage of the disease; 10% have pulmonary fibrosis.

• Dry cough

• Dyspnea that worsens upon/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

• Plaques

• Lupus pernio (specific for sarcoidosis)

• Erythema nodosum is the (most common skin manifestation); referred to as Lofgren syndrome when it occurs with x-ray findings of bilateral hilar or paratracheal adenopathy and joint involvement

• Subcutaneous nodules

• Neurologic: Given such a range of neurological involvement, patients may present with virtually any neurological 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, shows decreased glucose, increased protein, increased lymphocytes)

• Involvement of the hypothalamic-pituitary axis (manifests with pituitary insufficiency, optic chiasm compression, DI)

• Seizures

• Vasculitis

• Stroke/transient ischemic attack

• Peripheral neuropathy (possibly manifesting with paresthesias and decreased deep tendon reflexes [DTRs])

Physical:

• Skin

• Skin plaques and lesions

• Lupus pernio (violaceous lesions on face and/or extremities)

• Erythema nodosum (red painful lesion on 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.

  • 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); is 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 its hematological 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

• Clinically significant renal failure (uncommon)

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

DIFFERENTIALS

Section 4 of 12

Arthritis, Rheumatoid
Multiple Sclerosis
Pericarditis and Cardiac Tamponade
Pneumothorax, Iatrogenic, Spontaneous and Pneumomediastinum
Pulmonary Embolism
Systemic Lupus Erythematosus
Tuberculosis

Other Problems to be Considered:

Angina
Bronchitis
Fungal pneumonia
Histiocytosis X
Leprosy
Lymphoma
Lung cancer
Pulmonary alveolar proteinosis (PAP)
Pneumoconiosis (eg, silicosis, berylliosis)

WORKUP

Section 5 of 12

Lab Studies:

• Complete blood count

• Leukocytosis

• With or without eosinophilia

• Elevated erythrocyte sedimentation rate (ESR)

• Hypercalcemia is observed in 10-15% of cases. (It may be helpful to remember the mnemonic "Pam P. Schmidt," in which P represents parathyroid hormone [PTH], A represents Addison, M represents multiple myeloma, P represents Paget, S represents Sarcoidosis [or other granulomatous disease], C represents cancer [lungs, multiple myeloma, breast], M represents milk alkali syndrome, I represents immobilization, D represents vitamin D, and T represents thiazides). Although hypercalcemia is present by definition, it is rarely clinically significant. If other organs are involved, such as the liver, kidney, or endocrine, laboratory results pertinent to these organs are abnormal.

• The serum PO₄ and alkaline phosphatase can be increased.

• A 24-hour urinalysis assessment indicates that calcium levels are increased.

• A slit lamp examination generally is obtained periodically, even if the patient is asymptomatic.

• Immunologic studies can show falsely elevated antinuclear antibodies (ANA), rheumatoid factor (RF), and hypergammaglobulinemia.

• Patients with sarcoidosis may have myocardial involvement and elevated creatine kinase (CK) and CK-MB levels.

Imaging Studies:

• Chest x-ray is an integral part of the diagnosis and staging. In addition, the x-ray may demonstrate pleural involvement, such as a pneumothorax or pleural effusion.

• Stage O - No findings

• Stage I - Hilar adenopathy

• Stage II - Hilar adenopathy and parenchymal involvement

• Stage III - Parenchymal involvement without adenopathy

• Stage IV - Pulmonary fibrosis

• Gallium 67 scanning is used for staging of disease and to detect extrapulmonary sarcoidosis. Gallium bound by inflammatory tissue and not by fibrotic tissue can distinguish areas of fibrosis from inflammation.

Other Tests:

• Skin anergy with PPD is common in sarcoidosis patients but obviously not specific.

• Kveim-Stilzbach test

• A suspension from the spleen or a lymph node of a patient with a confirmed diagnosis of sarcoidosis is injected intradermally into a patient suspected to be affected by the disease.

• Test results are considered positive if a nodule appears within 2-7 weeks.

• The nodule is then biopsied to find similarities to sarcoid granuloma.

• The time required for this test, the incidence of false-negative and false-positive results, and the availability of more timely diagnostic tests make this procedure unpopular in the United States.

• Electrocardiogram

• Signs of hypercalcemia (eg, decreased QT interval)

• Ventricular tachycardia

• Bundle branch block or complete heart blocks

• ST elevation, PR depression caused by pericarditis, or ST elevation caused by ventricular aneurysm

• A Holter monitor may be indicated to detect arrhythmias.

Procedures:

• Bronchoalveolar lavage

• A bronchoalveolar lavage (BAL) shows increases in the CD4/CD8 ratio, lymphocytes, and cytokines.

• Studies performed to correlate the presence of these markers with prognosis were not conclusive.

• Biopsy is an integral part of the diagnosis and is of very high yield.

• The site of biopsy is dictated by clinical presentation of the organ involved.

• The sensitivity is highest from lung parenchyma and 5-10 biopsies generally are needed.

• Pulmonary function tests (PFTs) are not required for diagnosis, but may range from reference range to findings consistent with restrictive lung disease.

TREATMENT

Section 6 of 12

Prehospital Care: Focus prehospital care on immediate or potential life threats. Initial assessment of the patient always begins with attention to the ABCs. Focus on respiratory support and ensuring adequacy of oxygenation because patients generally present with respiratory complaints.

• Provide supplemental oxygen to all patients. Patients with signs of impending respiratory failure should have ventilatory assistance with bag-valve-mask and high flow oxygen. Consider intubation if a patient's condition continues to deteriorate. Perform continuous pulse oximetry if available.

• Obtain intravenous access for all patients except those who have minimal complaints. Provide judicious fluid boluses to patients with evidence of dehydration.

• Monitor cardiac function of all patients with a history of sarcoidosis because the potential for cardiac involvement exists.

• Because many patients with sarcoidosis are treated with steroids, consider the possibility of altered glucose metabolism and perform blood glucose determinations.

Emergency Department Care: Perform a primary evaluation of the ABCs. Because pulmonary complaints predominate, pay attention respiratory effort, monitor oxygenation, and evaluate for evidence of respiratory failure.

All patients should be provided with supplemental oxygen. Patients with impending or obvious respiratory failure should have ventilatory assistance with bag-valve-mask and high-flow oxygen. Patients with respiratory failure should be intubated and placed on ventilator control.

Perform pulse oximetry tests. Hypoxemic patients and those with evidence of respiratory failure should have arterial blood gas determination. With the possibility of cardiac involvement, cardiac monitoring is generally indicated. Consider intravenous access and administration of fluid boluses to patients with evidence of volume depletion.

Because sarcoidosis patients may have taken long courses of steroids, consider alteration in glucose metabolism and the possibility of secondary adrenal insufficiency. Blood glucose determination, urinalysis, and serum chemistries may be indicated.

Sarcoidosis generally is treated with steroids, but this is not endorsed by all physicians. The dosage and duration of treatment varies among institutions and studies because the prognosis is difficult to determine with the course of the disease varying from one individual to another; however, a consensus exists among most physicians to treat symptomatic patients and patients who show signs of deterioration from baseline. These guidelines are discussed below and are arbitrarily classified into pulmonary and extrapulmonary.

• Pulmonary
  • Stage I-III: If the patient is asymptomatic and pulmonary function test (PFT) results are normal, the patient is monitored for a few weeks with x-rays and PFTs. If symptoms worsen, steroids are begun.

  • Patients in Stage IV are symptomatic and treated with steroids. Even though stage IV stands for pulmonary fibrosis, patients taking steroids show improvement probably because the steroids act on ongoing inflammation.

  • Other agents, mainly cytotoxic medications, also have been used in the treatment of sarcoidosis; however, success has been variable.

  • Consider a lung transplant if the patient does not respond to standard therapy or the disease is in the end stage.

  • Pulmonary symptoms may vary from dyspnea on exertion to severe respiratory failure. Patients require supplemental oxygen, pulse oximetry, ABGs, a chest x-ray, and intubation when indicated.

  • Review of the patient's medication is mandatory. If patient is not taking any medications or if the patient's medication dosage was recently changed, it is reasonable to start and/or restart them on medications.

  • In most cases, when symptoms are severe, 60 mg of prednisone daily is prescribed. In moderate cases, 40-60 mg of prednisone every other day is sufficient and tapered after 6 months by 5 mg per month. Many patients are treated with a maintenance dose of 20 mg.

  • It is mandatory to rule out other pulmonary pathologies, such as pneumonia (eg, bacterial, fungal, Pneumocystis carinii pneumonia [PCP]), CHF, or pulmonary hypertension.

• Extrapulmonary
  • The heart can manifest with mechanical and/or conduction defects. Standard treatment is indicated (see below). Holter monitoring is indicated in the outpatient setting. CNS or peripheral neuropathy is treated with systemic steroids.

  • Patients may present with CHF (diuretics and/or inotropics are the mainstays of therapy) or arrhythmias (eg, bundle branch blocks, atrioventricular [AV] blocks). ECG, chest x-ray, and telemetry are indicated. Cardiac manifestations are treated in the usual fashion with diuretics and inotropics, as indicated. Recently, steroids and other immunosuppressive treatments showed an improvement in 87% of patients and a cure in 54% of patients from a clinical and laboratory point of view.

• The eye commonly is involved in sarcoidosis. Topical steroids may be sufficient. Ocular manifestations can present with uveitis or conjunctivitis. A slit lamp examination and/or ophthalmology consultation is mandatory. Treatment is with local or systemic steroids.

• CNS manifestations may present with cranial nerve symptoms (eg, VII, IX, X), with signs of optic chiasm involvement (eg, papilledema, blurred vision), meningeal symptoms caused by aseptic meningitis (requires a lumbar puncture [LP] for confirmation), Symptoms of stroke/transient ischemic attack, decreased DTR, and paresthesias (caused by peripheral neuropathies).

• A CT scan of the head, MRI, and neurological consultation are appropriate. Once it is established that neurologic symptoms are secondary to sarcoidosis, systemic steroids are started.

• Hypercalcemia is generally responsive to IV hydration. If this is not sufficient or ECG manifestations are present, systemic steroids are indicated. In the outpatient setting, a decrease in sunlight exposure and sometimes ketoconazole (decreases 1,25-dihydroxyvitamin D) are helpful in minimizing hypercalcemia and hypercalciuria.

• Skin manifestations are treated with topical or systemic steroids. Methotrexate and retinoids are used occasionally. A dermatological consultation is suggested.

• Arthritis generally is treated with NSAIDs. Steroids and occasionally colchicine are reserved for severe cases.

• Asymptomatic elevation of LFTs does not require treatment.

Consultations: Consider consultations with other services, such as pulmonology, neurology, dermatology, ophthalmology, GI, and rheumatology, for all patients, except those with minimal findings. Patients considered for discharge should meet with a specialist in managing sarcoidosis for appropriate follow-up treatment.

MEDICATION

Section 7 of 12

The goal of treatment is to minimize the inflammatory process. Generally, all medications are started when the patient is symptomatic or worsening. Two major categories in the treatment of this disease are steroids and cytotoxics.

Drug Category: Glucocorticoids -- These agents minimize the activity of inflammatory cells and the formation of granulomas. They are used in symptomatic patients, and they commonly provide symptomatic improvement. Glucocorticoids administered through inhalation or intravenous infusions do not show significant benefit over oral dosage forms.

Drug Name	Prednisone (Deltasone) -- Used in the treatment of various allergic and inflammatory diseases. Decreases inflammation by reversing increased capillary permeability and suppressing PMN activity. Treatment should be followed with x-rays and PFTs before deciding when to taper the dose. Some patients are treated with long-term steroid therapy. When a satisfactory response is attained, taper by 5 mg/mo until a dose of 20 mg qd or qod is achieved.
Adult Dose	0.05-2 mg/kg/d PO divided bid/qid for 4 wk
Pediatric Dose	4-5 mg/m2/d PO; alternatively, 1-2 mg/kg PO qd; taper as in adults
Contraindications	Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI disease
Interactions	Coadministration with estrogens may decrease clearance; concurrent use with digoxin, may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Drug Category: Cytotoxic agents -- Antineoplastic (cell cycle and phase specific) and may inhibit T-cell production (how it is effective in sarcoidosis).

Drug Name	Methotrexate (Folex, Rheumatrex) -- Antimetabolite that inhibits DNA synthesis and cell reproduction in malignant cells and may suppress the immune system.
Adult Dose	10 mg PO qwk for 30 mo
Pediatric Dose	5-15 mg/m2/wk PO/IM as a single dose or as 3 divided doses given 12 h apart
Contraindications	Documented hypersensitivity; alcoholism, hepatic insufficiency, documented immunodeficiency syndromes, preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia)
Interactions	Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate (MTX); charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response to MTX; coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity; may increase plasma levels of thiopurines
Pregnancy	D - Unsafe in pregnancy
Precautions	Monitor CBCs monthly, and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels [eg, dehydration] exists); Has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood counts; aspirin, NSAIDs, or low dose steroids may be administered concomitantly with MTX (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested)

FOLLOW-UP

Section 8 of 12

Further Inpatient Care:

• Patients with severe pulmonary and/or extrapulmonary symptoms must be admitted to the hospital.

• Prednisone treatment is instituted as discussed above. If symptoms are refractory those listed above, if multiorgan involvement occurs because of concomitant failure, or if infection is present, it is prudent to place the patient in an intensive care unit (ICU).

• In the hospital, patients may benefit from pulmonary physical therapy. This decision must be made in conjunction with the physical therapy (PT) department. PT can achieve energy conservation, incentive spirometry, segmental breathing exercises, teaching positions to relieve breathlessness, and interval exercise training to improve aerobic capacity.

Further Outpatient Care:

• As discussed above, once prednisone therapy is started, it is continued for 4 weeks to 6 months before tapering the dosage.

• Use the following as routine parameters to assure a favorable outcome:

• Obtain a chest x-ray.

• Perform pulmonary function testing.

• Occasionally, a Gallium 67 scan is performed to assess involvement of extrapulmonary organs and to distinguish between inflammatory and fibrotic processes.

• Serial BAL fluid studies for measurement of cytokines and CD cell ratio, although not predictive of prognosis and severity of disease, are used in certain institutions to monitor the response to therapy.

• ACE levels (as BAL) have no prognostic value but serial results can help to assess the therapeutic response.

• Carefully monitor medication adverse effects, serum chemistries to measure calcium, blood urea nitrogen, and creatinine, liver function tests; perform periodic slit lamp examinations.

• Outpatient physical therapy may improve the patient's quality of life.

In/Out Patient Meds:

• Prednisone is an oral steroid and the mainstay of medical treatment. Base dosage on the patient's symptoms.

• When failure to steroid treatment and progression of disease is evident, other empiric treatments, such as cytotoxics (eg, methotrexate) are tried. Lung transplant is an option when the patient is refractory to medical therapy and end-stage pulmonary failure is present. Cases of new-onset sarcoidosis in transplanted lungs have been documented.

Transfer:

• Consider transfer to a specialized center for patients who are not responding to standard therapy or if lung transplant is entertained.

• Before transfer, ensure that the patient has stable vital signs and a good or acceptable oxygen saturation level, ECG finding, and mental status.

Deterrence/Prevention:

• Although it is intuitive that smoking may worsen pulmonary sarcoidosis, many studies indicate the contrary.

• Consider measures to protect patients from pulmonary diseases, such as influenza (with flu vaccine), bronchitis, or PCP (patients may benefit from low dose prophylactic trimethoprim/sulfamethoxazole treatment if taking long-term steroid therapy).

Complications:

• Complications are organ specific and variable, as follows:

• Pulmonary - Infections, pulmonary hypertension, pulmonary fibrosis, and death

• Cardiac - Arrhythmias and CHF

• Ocular - Uveitis and conjunctivitis

• Liver - Commonly involved but rarely clinically significant

• Lymphatic - Evidence of hypersplenism

Prognosis:

• Two thirds of cases resolve spontaneously, one third are long-term, and 5% result in fatality.

• Although no markers exist to accurately predict outcome, certain traits and features can suggest a prognosis, as follows:

• Acute presentation, erythema nodosum, and stage I x-ray manifestations are considered favorable prognostic features, and remission may occur in 2-5 years.

• Stage III-IV, chronic iritis, lupus pernio, tracheal involvement, and extrapulmonary manifestations are associated with less favorable prognosis.

• Genetics also may have a role. Black persons have a less favorable prognosis than white persons. Patients with HLA-B13 also have less favorable prognosis than patients with HLA-B8. The correlation between advanced cases of sarcoidosis and G-6-PD are described.

Patient Education:

• Discuss compliance with medications and medical follow-up.

• Educate about extrapulmonary complications (eg, uveitis, arrhythmias) and importance of seeking immediate medical attention.

MISCELLANEOUS

Section 9 of 12

Medical/Legal Pitfalls:

• Failure to consider other entities with similar presentation. Tuberculosis and lymphoma are particularly important in the United States.

• Consider possibility of other life-threatening conditions (eg, pulmonary embolism) if no evidence of sarcoidosis is documented in the ED and a patient complains of dyspnea.

• Failure to recognize or ignore complaints (eg, ocular symptoms, chest pain) is a pitfall. Ignoring these complaints may indicate that the ED physician is not aware of the complications that can occur with sarcoidosis.

• To merit transfer to another hospital, all criteria must be present. In the case of sarcoidosis, ensure that vital signs, oxygen saturation levels, ECG findings, and mental status are acceptable.

• Failure to emphasize the need for follow-up treatment is a pitfall.

• Failure to explain the complications and symptoms that require immediate medical attention.

TEST QUESTIONS

Section 10 of 12

CME Question 1: A 40-year-old woman and member of Alcoholics Anonymous presents to the ED with complaint of dyspnea for a few weeks. Further questioning of the patient reveals constitutional symptoms. The physical examination is not diagnostic, and the physician orders a chest x-ray. On the basis of the above findings, which of the following may be the correct diagnosis?

A: Tuberculosis (TB)
B: Lymphoma
C: Atypical pneumonia
D: Interstitial lung disease
E: All of the above

The correct answer is E: Sarcoidosis is a diagnosis of exclusion; other more common diseases with constellations of constitutional symptoms and radiographic changes must be considered in differential. While the other entities are excluded, a biopsy must be performed to detect noncaseating granulomas and to confirm the diagnosis of sarcoidosis. The ED physician`s role is to consider the worse case scenario and act on it. In the above case, if TB is suspected in the differential, the patient must be isolated until it is excluded.

CME Question 2: A 40-year-old white man presents to the ED with complaints of bilateral facial numbness and an inability to smile. After a thorough examination, bilateral facial palsy and ptosis is documented. Which of the following should be considered?

A: CT scan of the head to rule out stroke
B: Possibility of Lyme disease
C: Possibility of Miller-Fisher disease (ie, idiopathic polyneuritis, bulbar Guillain-Barré)
D: Consultation with a neurologist
E: All of the above

The correct answer is E: When diagnosing sarcoidosis, other diseases must be considered in the differential. The patient in the case described had a chest x-ray that is consistent with stage I sarcoidosis. A subsequent biopsy confirmed the diagnosis.

Pearl Question 1 (T/F): Steroids are an important management of sarcoidosis and should be administered to patients presenting to the ED with worsening symptoms.

The correct answer is True: Patients who take steroids show improvement probably because steroids act on ongoing inflammation.

Pearl Question 2 (T/F): Biopsy is an integral part of the diagnosis of sarcoidosis.

The correct answer is True: Biopsy is an integral part of the diagnosis and is of very high yield. The site of biopsy is dictated by clinical presentation of the organ involved. The sensitivity is highest from lung parenchyma and, generally, 5-10 biopsies are needed.

Pearl Question 3 (T/F): Hypercalcemia is an important electrolyte abnormality associated with sarcoidosis and should be evaluated in the ED.

The correct answer is True: Hypercalcemia is a significant electrolyte abnormality associated with sarcoidosis. Patients also may have increased creatine kinase (CK) and CK-MB fraction. Unless coronary artery disease (CAD) and myocardial infarction (MI) are located high in the differential, these findings are probably caused by myocarditis.

Pearl Question 4 (T/F): The elevated liver function tests (LFTs) observed in sarcoidosis require treatment.

The correct answer is False: Elevated LFTs do not require management.

PICTURES

Section 11 of 12

Caption: Picture 1. Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.
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Caption: Picture 2. Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.
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Caption: Picture 3. Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.
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Caption: Picture 4. Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.
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Caption: Picture 5. Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.
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Caption: Picture 6. Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.
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BIBLIOGRAPHY

Section 12 of 12

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