Medical Therapy for Rheumatic Disorders
Medications are used in rheumatology for several purposes, including analgesia, control of inflammation, and immunosuppression. The use of these drugs in treating ocular inflammatory diseases is discussed in BCSC Section 9, Uveitis and Ocular Inflammation.
Glucocorticoids decrease inflammation by inhibiting the breakdown of phospholipid to arachidonic acid and blocking the production of inflammatory mediators, including prostaglandins and leukotrienes. Glucocorticoids have a variety of other systemic effects apart from their anti-inflammatory activity. They promote gluconeogenesis, with a concomitant negative nitrogen balance and reduction in protein production. Fat oxidation, synthesis, storage, and mobilization are also affected. After glucocorticoid administration, the number of circulating neutrophils increases because mature neutrophils are released from bone marrow, and their movement from the blood into other tissues is reduced, while the number of other circulating leukocytes decreases. Associated mineralocorticoid activity increases sodium retention and potassium excretion.
Table 9-4 lists the relative potency of commonly used glucocorticoid preparations. The molecular structure of the corticosteroid nucleus can be modified to dissociate glucocorticoid from mineralocorticoid activity. Unfortunately, isolating the beneficial anti-inflammatory effects from the less desirable glucocorticoid effects has not been fully achieved. The ophthalmologist must be aware of the ocular and systemic toxicities associated with systemic corticosteroids.
Table 9-4 Potency of Commonly Used Glucocorticoids
Ocular adverse effects of systemic corticosteroids include posterior subcapsular cataracts, glaucoma, mydriasis, ptosis, papilledema associated with idiopathic intracranial hypertension, worsening of ocular infection, and delay in wound healing. Systemic complications may include peptic ulceration, osteoporosis, and aseptic necrosis of the femoral head, as well as muscle and skin atrophy. Steroids can also cause hyperglycemia, hypertension, edema, weight gain, and changes in body fat distribution, resulting in a cushingoid habitus. Other adverse effects include hyperosmolar nonketotic states, hypokalemia, and growth delay in children. Mental changes are a common problem, ranging from mild mood alterations to severe psychological reactions, including psychological dependence.
Osteoporosis is a significant problem that can increase the risk of fractures as early as a few months after beginning corticosteroid therapy. Bone mineral density testing is used to assess the degree of osteoporosis. In addition to calcium and vitamin D supplementation, hormone replacement therapy and bisphosphonates are sometimes initiated.
Cessation of therapy
Rapid withdrawal of systemic corticosteroid therapy can cause complications. The rate of corticosteroid withdrawal is determined by 2 criteria: (1) the degree of hypothalamicpituitary-adrenal (HPA) suppression, which in turn is related to steroid potency, dose, and duration of therapy, and (2) the response of the underlying disease to the corticosteroid withdrawal. HPA suppression is likely present in patients who have a cushingoid appearance or who have received a glucocorticoid equivalent daily dose greater than or equal to 10 mg of prednisone (alternatively, a continuous evening or bedtime dose of ≥5 mg) for more than 3 weeks. HPA suppression is reduced below these parameters. When tapering becomes necessary, a practical approach is to reduce steroid requirement by 5% to 10% every 2 to 4 weeks while monitoring response carefully. Otherwise, sudden cessation of corticosteroid therapy could result in adrenal insufficiency, with symptoms such as fatigue, weakness, arthralgias, nausea, orthostatic hypotension, and hypoglycemia. In severe cases, adrenal suppression may be fatal.
After corticosteroid therapy has been discontinued, adrenal function may not return to normal for a year or more, and coverage with supplementary corticosteroids may be required if the patient has a serious illness or undergoes surgery during this recovery period.
Ophthalmologists who initiate systemic corticosteroid therapy for ophthalmic diseases should consider requesting assistance from the patient’s primary care provider to monitor for adverse effects. For patients who require high-dose or extended corticosteroid treatment, clinicians should strongly consider early use of other immunosuppressive medications, which can decrease patient dependency on, and long-term complications of, corticosteroid use.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.