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Glucocorticoid Treatment of Symptomatic Sarcoidosis in 2 Morbidly Obese Patients

Corticosteroid management for patients with sarcoidosis requires the need for close monitoring to detect and manage any complications that may arise during treatment.
Federal Practitioner. 2019 January;36(1):36-40
January 10, 2019|Federal Practitioner
Lauren F. Comisar, MD;Michael M. Rey, MD;Mitchell L. Margolis, MD
Author and Disclosure Information

Lauren Comisar is a Resident Physician in the Internal Medicine Department at New York Presbyterian/Weill Cornell Medical College in New York City. Michael Rey is a Fellow Physician, and Mitchell Margolis is a Clinical Professor of Medicine, both in the Division of Pulmonary, Allergy, and Critical Care Medicine at the Hospital of the University of Pennsylvania in Philadelphia. Mitchell Margolis also is Chief of Pulmonary and Critical Care Section at the Michael J. Crescenz Veterans Affairs Medical Center in Philadelphia.
Correspondence: Michael Rey (michael. rey@uphs.upenn.edu)

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Discussion

These 2 cases highlight therapeutic challenges that may arise in the management of sarcoidosis with symptomatic vital organ involvement and coexistent extreme obesity. Both patients showed symptom improvement with moderate doses of prednisone (40 mg to 50 mg daily), but serious treatment-related complications developed: further weight gain in the first patient, and severe DM in the second. Although DM may have been a direct treatment complication in our second patient, his HFpEF and PH were high-risk comorbidities; he did not present with acute symptomatic worsening after treatment initiation. His symptoms were never reassessed when he was lost to follow-up.

Sarcoidosis/Obesity Relationship

Recent evidence suggests that patients with obesity are at increased risk of developing sarcoidosis.5-7 Although the mechanism of association is unclear, several possibilities have been proposed.

Neurosarcoidosis. One known but rare cause of obesity is neurosarcoidosis of the hypothalamus or pituitary.14 This was investigated in one of our patients.

Proinflammatory responses. Another possible mechanism for the association of sarcoidosis and obesity is the proinflammatory properties of increased fat and adipose tissue.15 Obesity has been linked to an aberrant expansion of inflammatory cells and mediators, including macrophages, proinflammatory cytokines, T cells, and B cells.15 Leptin, produced primarily by adipocytes, also is higher in obese patients and has been found to be proinflammatory.16 These seem to underlie the link between obesity and other inflammatory diseases, including type 2 DM, gout, and atherosclerosis.15

Behavioral link. There also is a possible behavioral link between sarcoidosis and obesity: A patient might develop symptomatic sarcoidosis and later become less active due to dyspnea, which could predispose to weight gain.5

Management of Comorbid Sarcoidosis and Obesity

Regardless of the exact mechanism of this association, management of the co-occurrence of sarcoidosis and obesity poses a clinical problem, especially in cases of extreme obesity. Corticosteroids are generally considered the treatment of choice for symptomatic sarcoidosis. The initial treatment of symptomatic pulmonary sarcoidosis is 20 mg to 40 mg prednisone daily.10,11 Higher daily doses such as 60 mg to 80 mg or 0.5 mg/kg are typically used to treat cardiac sarcoidosis, although no clear consensus exists on the appropriate dose.12,17 One recent study showed no difference in cardiac outcomes in patients treated with high- and low-dose prednisone.18

For patients who are obese and require steroids to treat a medical condition, there is conflicting evidence on whether steroid doses should be increased in proportion to total body weight. Milsap and colleagues found clearance of prednisolone correlated strongly with degree of obesity, suggesting steroid dose should be increased in accordance with actual weight.19 In contrast, Dunn and colleagues found decreased clearance of methylprednisolone in obese patients, suggesting that ideal body weight dosing is appropriate.20

Identifying the appropriate steroid dose is important because corticosteroids place obese patients at higher risk of developing complications. Treatment-related comorbidities include DM, hypertension, fluid retention, osteoporosis, and infection. Further weight gain due to steroid use is a risk for progressive OSA and, even though not generally associated with sarcoidosis alone, OHS. For patients with sarcoidosis, these complications (DM, fluid retention, hypertension, sleep-disordered breathing) may increase the risk of cardiovascular disease and PH.21-23 Cardiomyopathy, especially with reduced EF and increased PH, can be associated with a poor prognosis in sarcoidosis.4,24-26 PH also can be challenging to treat patients with sarcoidosis because the response of PH to steroids is unclear.27 Small trials have shown the benefit of pulmonary vasodilators on hemodynamics, but these have generally been used in patients with stable sarcoidosis who do not have left-heart disease.28-30

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