Sarcoidosis

Article Author:
Syed Rizwan Bokhari
Article Editor:
Abeera Mansur
Updated:
2/28/2019 10:46:37 PM
PubMed Link:
Sarcoidosis

Introduction

Sarcoidosis is a multisystem disorder of unknown etiology that mostly affect young adults worldwide and presents with noncaseating granulomas in various organs. Characteristically it presents with bilateral hilar lymphadenopathy and reticular opacities in lungs. Other major involved sites include skin, eyes, and joints, although it can express to a variable degree in the musculoskeletal system, reticuloendothelial system, exocrine glands, heart, kidney, and central nervous system.[1][2][3]

Etiology

It is an inflammatory disease of unknown etiology that manifests as noncaseating granulomas in multiple systems. Various associations have been described, including occupational and environmental exposures to beryllium, dust, and other agents causing asthma. Various microorganisms like mycobacteria and propionibacteria have been associated. Possible infective etiology has been described in few studies where sarcoidosis developed in a previously negative individual after cardiac or bone marrow transplantation.[4][5]

Genetic component and disease in more than one family member are usually related with antigens of the major histocompatibility complex (MHC), especially DR alleles. Few studies have described other less common genomes and angiotensin converting enzyme genotypes in few patients.

Cytokines including Th1, IL-2, IL6, IL 8, IL12, IL 18, IL 27, and interferon (IFN) gamma, and tumor necrosis factor (TNF) alpha are closely associated with sarcoidosis. Few of these are implicated in granuloma formation with macrophage and epithelioid accumulation, activation, and aggregation. Some of these Interleukins are believed to act as disease modifiers.

Epidemiology

The incidence is 11 cases per 100,000 population in whites but 34 cases per 100,000 population in African Americans with a lifetime risk of 2.4 percent in the USA. Extrapulmonary sarcoid is seen in up to 25 to 30 percent of patients. Cardiac involvement is seen more commonly in males while skin and eye features are more prominent in women. Extrapulmonary features can be different in terms of age of presentation, gender, and ethnicity.[6][7]

Pathophysiology

Pathogenesis of cutaneous sarcoidosis is poorly understood and attributable to both genetic and environmental factors. Key role in the development of sarcoidosis is played by T cells as they promote cellular immune reaction and usually associated with an inverted CD4/CD8 ratio. It is well characterized by noncaseating granuloma typically containing macrophages, multinucleated giant cells and epithelioid cells, in addition to lymphocytes, monocytes, mast cells, and fibroblasts  There is a role of tumor necrosis factor (TNF) and TNF receptors, both are increased in this disease.  This has been explained by the role of anti-TNF agents, such as pentoxifylline and infliximab. In addition to T cells role, B cell hyperreactivity with immunoglobulin production is implicated as well. Active sarcoidosis has also been associated with plasmatic hypergammaglobulinemia. Angiotensin-converting enzyme (ACE) levels correlated with elevated Soluble HLA class I antigens levels in serum.[8]

Histopathology

Biopsy of lymph nodes will reveal non-caseating granulomas.

History and Physical

Symptoms are variable; typically patients present with persistent dry cough, fatigue, and shortness of breath. Other symptoms include painful red lumps on the skin, uveitis with the blurring of vision, hoarseness of voice, palpable lymph nodes at multiple sites including armpit, neck, painful swollen joints, hearing loss, seizures, or psychiatric disorders could be observed as part of neurological manifestations. Cardiomyopathy, conduction defects, renal calculi and enlarged liver are observed in few cases.

A wide range of cutaneous manifestations can be classified as papular, maculopapular, nodular, subcutaneous, hypopigmented and plaque sarcoidosis. Most common lesions in cutaneous sarcoidosis are Papular sarcoidosis involving the upper half of face, back of neck and previous trauma /scar sites and tattoos A variant of cutaneous sarcoidosis that presents with violaceous or erythematous papules, plaques, or nodules mainly involving the central facial skin is called lupus pernio. Other well-described skin manifestations of sarcoidosis include nodular sarcoidosis. Plaque-like lesions and subcutaneous nontender nodules are also commonly seen.

Erythema nodosum (EN) is seen in a variety of other conditions including sarcoidosis and usually presents with painful nodules on shins. It is characterized as panniculitis and is a part of Lofgren syndrome. Skin lesions can appear up to 10 or more years after the initial injury or tattoo.

Evaluation

Lab tests:

  • Complete blood count and differential looking for anemia, leukopenia nd thrombocytopenia, liver function tests, blood urea nitrogen, creatinine, glucose, electrolytes, serum calcium looking for hypercalcemia. ESR and c-reactive protein are nonspecific tests, often elevated.
  • Elevated serum alkaline phosphatase concentration suggests diffuse granulomatous hepatic involvement.
  • Serologic tests including serum angiotensin converting enzyme (ACE), adenosine deaminase, serum amyloid A, and soluble interleukin-2 receptor can be considered.
  • Kveim test is similar to tuberculin skin test and evokes a sarcoid granulomatous response. It is of limited significance.

Radiographic tests:

  • Lungs are the main site of involvement; imaging tests include chest radiograph, CT Chest, fluorine-18-fluorodeoxyglucose-positron emission tomography (FDG-PET), gallium-67, thallium-201, technetium sestamibi (MIBI-Tc) and single photon emission computed tomography (SPECT).
  • Cardiac or CNS affected sarcoidosis is better diagnosed with the help of MRI or PET scan.

Radiographic stages are as follows:

  • Stage I: Presence of bilateral hilar adenopathy
  • Stage II: Bilateral hilar adenopathy and reticular opacities
  • Stage III: Reticular opacities with shrinking hilar nodes ( mainly infiltrates)
  • Stage IV: Reticular opacities with Fibrosis

In the case of clear chest X-ray in a patient with unexplained dyspnea or a cough, (HRCT) of the chest should be considered.

Histopathology: characteristically noncaseating granulomas, with aggregates of epithelioid histiocytes, giant cells, and mature macrophages are seen.

In order to rule out systemic disease, pulmonary function test, electrocardiogram, echocardiography, urinalysis and tuberculin skin testing should be considered.

Follow-up of pulmonary disease can be done with pulmonary function tests and a carbon monoxide diffusion capacity test of the lungs for carbon monoxide (DLCO).[9][10][11]

Treatment / Management

Pulmonary sarcoidosis is often asymptomatic, non-progressive disease and requires no treatment, as a majority of patients undergo spontaneous remission. Close monitoring of symptoms, chest radiograph, and pulmonary function is continued at three to six-month intervals should be considered in asymptomatic patients. Patients with pulmonary sarcoidosis causing worsening symptoms, stage II-III radiographic findings should be considered for oral glucocorticoids at 0.3 to 0.6 mg/kg for 4 to 6 weeks.  If there is no improvement in symptoms, radiographic abnormalities, and pulmonary function tests, steroids may be continued for additional four to six weeks. Maintainance steroids are not needed, steroid tapering to a dose of 0.25 to 0.5mg/kg (usually 10 to 20 mg) per day, should be considered over a period of at least six to eight months. Methotrexate, azathioprine, infliximab, leflunomide, and antimalarial agents may be considered as steroid-sparing agents in patients who are unable to tolerate steroids.[12][13]

Differential Diagnosis

  • Tuberculosis
  • Cat scratch disease
  • Lung cancer
  • Lymphoma
  • Occupational lung disease
  • Fungal infection

Enhancing Healthcare Team Outcomes

Sarcoidosis has no obvious cause and hence prevention is not possible. The disorder also resolves spontaneously and hence treatment is not always required. However, severe cases do need to follow up. The management of patients with sarcoidosis is best done in a multidisciplinary fashion with a team of healthcare workers that includes a cardiologist, neurologist, radiologist, pulmonologist, cardiac nurse, respiratory therapist and a pharmacist. The patient needs regular chest x-rays since it is a marker for disease progression. Some patients may benefit from pulmonary rehabilitation and use of bronchodilators. If the disease is advanced, a regular eye exam is important. In addition, the nurse should ensure that the patient gets a regular 12-lead ECG because heart block is not uncommon. The pharmacist should educate the patient on the importance of discontinuing smoking and abstaining from alcohol. Finally, patients who are managed with steroids should be educated about the side effects of these drugs. [14][15](Level V)

Outcomes

In many patients with sarcoidosis. No treatment is required and the disorder spontaneously resolves. However, in a certain number of people, the disease may take a fulminant course with severe symptoms. Factors that indicate a poor prognosis include significant chest imaging findings, extrapulmonary involvement and presence of pulmonary hypertension. Many studies indicate that the chest x-ray is an excellent marker for disease prognosis. In severe cases, patients may require oxygen, experience heart block and respiratory failure. Data regarding mortality are not available because in many cases long-term follow up is missing. Overall, it appears that about one-fifth of patients develop functional impairment and there is a mortality rate of 3-5% in patients who are not treated. The highest mortality rates are in African American females past the fifth decade of life. [16][17](Level V)



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References

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