pulmonary disorders
Sarcoidosis
Treatment of Sarcoidosis
Nonsteroidal anti-inflammatory drugs (NSAIDs) Corticosteroids Immunosuppressants Anti-tumor necrosis factor-alpha antibodies Because sarcoidosis often spontaneously resolves, asymptomatic patients and patients with mild symptoms do not require treatment, although they should be monitored for signs of deterioration. These patients can be followed with serial chest x-rays, pulmonary function tests (including diffusing capacity), and markers of extrathoracic involvement (eg, routine renal and liver function testing, annual slit-lamp ophthalmologic examination). The frequency of follow-up testing is determined by the severity of disease. Patients who require treatment regardless of chest x-ray stage include those with the following: Worsening symptoms Limitation of activity Markedly abnormal or deteriorating lung functions Worrisome x-ray changes (eg, cavitation, fibrosis, conglomerate masses, signs of pulmonary hypertension) Heart, nervous system, or eye involvement Renal or hepatic failure Moderate to severe hypercalcemia Disfiguring skin (eg, lupus pernio) or joint disease NSAIDs)are used to treat musculoskeletal discomfort. Symptom management begins with corticosteroids. The presence of chest imaging abnormalities without significant symptoms or evidence of decline in organ function is not an indication for treatment. A standard protocol isprednisone20 mg to 40 mg by mouth once a day, depending on symptoms and severity of findings. Alternate-day regimens may be used, eg,prednisone40 mg by mouth once every other day. Although patients rarely require > 40 mg/day, higher doses may be needed to reduce complications in severe neurologic and cardiac disease. Response usually occurs within 6 to 12 weeks, so symptoms, other disease-severity markers, and pulmonary function test results may be reassessed between 6 and 12 weeks. Chronic, insidious cases may respond more slowly. Corticosteroids are tapered to a maintenance dose (eg,prednisone10 to 15 mg/day) after evidence of response and are continued for an additional 6 to 9 months if improvement occurs. The optimal duration of treatment is unknown. Premature taper can result in relapse. The drug is slowly stopped if response is absent or equivocal. Corticosteroids can ultimately be stopped in most patients, but because relapse occurs up to 50% of the time, monitoring should be repeated, usually every 3 to 6 months. Corticosteroid treatment should be resumed for recurrence of symptoms and signs. Because angiotensin-converting enzyme (ACE) production is suppressed with low doses of corticosteroids, serial serum ACE levels may be useful in assessing adherence with corticosteroid treatment in patients who have elevated ACE levels. Inhaled corticosteroids can relieve cough in patients with endobronchial involvement. An inhaled bronchodilator can be added in patients with obstructive airway disease. Topical corticosteroids may be useful in dermatologic, nasal sinus, and ocular disease. Prophylaxis againstPneumocystis jiroveciipneumonia is recommended while patients are taking > 20 mgprednisonedaily or its equivalent for more than a month and for those who are taking immunosuppressants. Alendronateor another bisphosphonate may be the treatment of choice for prevention of corticosteroid-induced osteoporosis in people at risk (eg, older patients). Using supplemental calcium orvitamin Drisks hypercalcemia due to endogenous production of activevitamin D(1, 25 dihydroxyvitamin D) by sarcoidal granulomas. Serum and 24-hour urinary calcium measurements should be normal before starting such supplements. The presence of chest imaging abnormalities without significant symptoms or evidence of decline in organ function is not an indication for treatment with corticosteroids. Immunosuppressants are used when Patients cannot tolerateprednisone Sarcoidosis is refractory to moderate to high doses ofprednisone Prednisonedose cannot be tapered below 10 to 15 mg daily after 3 months Prior to adding other immunosuppressants, possible reasons for lack of clinical improvement, such as noncompliance, comorbid disease (eg, asthma, heart failure, anemia), pulmonary hypertension, and end-stage fibrosis should be considered. Methotrexateis the most commonly used immunosuppressant. Patients should be given a 6-month trial ofmethotrexate10 to 15 mg/week. Before startingmethotrexate, patients should be tested for infection with hepatitis B virus and hepatitis C virus. Initially,methotrexateand corticosteroids are both given; over 6 to 8 weeks, the corticosteroid dose can be tapered and, in many cases, stopped. The maximal response tomethotrexate, however, may take 6 to 12 months. In such cases,prednisonemust be tapered more slowly. Serial blood counts and liver enzyme tests should be done every 2 to 4 weeks initially and then every 6 to 12 weeks once a stable dose is achieved. Folate (1 mg by mouth once a day) is recommended for patients treated withmethotrexateto reduce the risk of adverse effects. Other immunosuppressants includeazathioprine,mycophenolate,cyclophosphamide,leflunomide, andhydroxychloroquine.Hydroxychloroquine400 mg by mouth once a day or 200 mg by mouth twice a day can be effective for treating hypercalcemia, arthralgia, skin sarcoidosis, or enlarged uncomfortable or disfiguring peripheral lymph nodes. Ophthalmologic evaluation should be done beforehydroxychloroquineis started and every 6 to 12 months during treatment to monitor for its ocular toxicity. Relapse is common after stopping an immunosuppressant. Infliximabis usually used as a 3rd-line medication to treat refractory sarcoidosis and to treat patients who are intolerant to both corticosteroid and the above-mentioned immunosuppressants. Before beginning therapy, patients should have a purified protein derivative (PPD) or interferon gamma release assay to screen for latent tuberculosis.Infliximabis given intravenously 3 to 5 mg/kg once, again 2 weeks later, then once per month. It may take 3 to 6 months for maximal response.Infliximabis usually combined with low-dosemethotrexateorazathioprineto prevent antibody formation against it. Adalimumabcan be considered for patients with ocular or cutaneus sarcoidosis and in patients who have been treated successfully withinfliximabbut have developed antibodies or infusion reactions.Adalimumab40 to 80 mg subcutaneously is given every 1 to 2 weeks. Patients who have heart block or ventricular arrhythmias due to cardiac involvement should receive an Implantable Cardioverter-Defibrillators (ICD) as well as drug therapy. No available drugs have consistently prevented pulmonary fibrosis. Treatment of sarcoidosis-associated pulmonary arterial hypertension (SPAH) is supportive with diuresis and supplemental oxygen. The role of pulmonary vasodilators in treating SPAH has not been well established; a few small studies have suggested efficacy, but larger studies are needed to confirm it ( Treatment reference ). Organ transplantation is an option for patients with end-stage pulmonary, cardiac, or liver involvement, although disease may recur in the transplanted organ. Patients with sarcoidosis and moderate or severe impairment of pulmonary or cardiac function are at increased risk of developing severe forms of COVID-19 and mortality. As in patients with other inflammatory lung diseases during the COVID-19 pandemic, immunosuppressants should be used judiciously. 1.Humbert M, Kovacs G, Hoeper MM, et al: 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.Eur Respir J61(1): 1-144, 2023. doi:10.1183/13993003.00879-2022 