Autoimmune blistering diseases (AIBD) often require high-dose corticosteroids and immunosuppressive agents for adequate control. These diseases cause significant morbidity but treatment can also lead to side effects and complications. This article reviews the supportive management of AIBD and the management of corticosteroid-induced side effects. The prevention and management of secondary effects from some of the more commonly used steroid-sparing agents for AIBD are summarized. Clinicians must be familiar with this information to optimally manage patients with AIBD.
Autoimmune blistering diseases (AIBD) are a group of antibody-mediated disorders that cause painful and disfiguring skin lesions, often leading to significant morbidity and mortality. In addition, complications secondary to the numerous therapies for AIBD contribute significantly to the clinical course of patients with this condition. The side effects of treatment, particularly systemic corticosteroids, may supersede the effects of the disease itself.
Bullous diseases affecting the mucous membranes lead to painful oral erosions, which in turn affect the patient’s ability to eat or drink. Weight loss, malnutrition, and loss of protein may occur in affected patients over time. Malnutrition leads to increased risk of secondary infection in these exposed areas. Cutaneous erosions compromise the barrier function of the skin and these denuded areas, much like thermal injury, and may lead to volume depletion and infection.
Side effects from medications used to treat AIBD can be troublesome. Corticosteroid-related side effects include immunosuppression, diabetes mellitus, osteoporosis, psychological effects, and peptic ulcer disease, to name a few ( Table 1 ). The emotional impact of AIBD on affected patients can be profound, including feelings of anxiety, depression, frustration, and fear. Although steroid-sparing agents may prevent steroid-related side effects, they have their own share of adverse effects as well, including bone marrow suppression, hepatotoxicity, nephrotoxicity, and anaphylaxis. It is vital to collaborate with the patient’s primary care physician to aid in the management of these conditions.
| Side Effect | Management |
|---|---|
| Adrenal insufficiency (weakness, fatigue, myalgias, arthralgias, syncope) | Avoid sudden decrease or discontinuation of corticosteroids; replenish corticosteroids; consultation with endocrinologist |
| Avascular necrosis of femur or humerus | Monitor for hip and shoulder pain; radiologic studies; consultation with orthopedic surgeon |
| Cataracts and glaucoma | Review history of visual problems at each visit; consultation with ophthalmologist |
| Central nervous system toxicity | Monitor for mood swings, psychosis, insomnia, and suicidal thoughts |
| Delayed wound healing, easy bruising, and thin easily torn skin | Avoidance of trauma; good wound care |
| Diabetes mellitus | Monitor glucose and hemoglobin A 1C levels; may require treatment with oral hypoglycemics or insulin |
| Electrolyte imbalance (increased sodium level, decreased potassium level) | Monitor electrolytes and replace as necessary |
| Fluid retention and lower extremity edema | Prevent with low-salt diet, potassium-sparing diuretics, and support hose |
| Gastrointestinal bleeding | Monitor for anemia; may need to check stool for blood; consultation with gastroenterologist |
| Hypertension | Antihypertensive agents |
| Infection (bacterial, fungal, viral, reactivation of tuberculosis) | Culture; PPD (purified protein derivative) testing; quantiferon testing; antimicrobial agents |
| Menstrual irregularities | May require hormonal therapy if severe |
| Myopathy and weakness | Adjustment of corticosteroid dose |
| Osteoporosis, particularly in postmenopausal women | Bone densitometry testing; treatment with bisphosphonates, calcium, vitamin D, and estrogen |
| PCP ( Pneumocystis carinii pneumonia) prophylaxis (in those receiving rituximab) | Double-strength trimethoprim/sulfamethoxazole 3 times per wk |
| Peptic ulcer disease | Oral corticosteroids best if given after meal to prevent ulcers; prevent or treat with H 2 blockers, proton pump inhibitors, and sucralfate |
| Skin changes (acne, folliculitis, striae, increased growth of unwanted body hair) | Antiacne medications; prevention of weight gain; depilatories; epilation |
| Weight gain and cushingoid features | Healthy diet; regular exercise |
Over the last few decades, morbidity and mortality rates in patients with AIBD have improved for several reasons. New therapeutic modalities have been shown to lower the use of steroids. Earlier recognition and precise diagnosis allow for earlier institution of therapy and milder course of disease. Improved medical and surgical therapy for the numerous complications and more appropriate use of steroids have also lowered the mortality risk.
Patients who present acutely, particularly those with many blisters and erosions, must receive general medical care in addition to skin-directed therapy. Supportive treatment includes oral or parenteral fluids and caloric nutrition. If a patient is unable to swallow because of mucous membrane lesions, a feeding tube or parenteral nutrition may be necessary. Heat loss may lead to chills and thermal dysregulation, requiring the use of blankets and a heated environment. Gentle whirlpool without debridement is helpful to remove necrotic skin. The skin must not be scrubbed to prevent further extension of erosions. Topical bland ointments and pain control are essential for patient comfort. Dressings must avoid tape at all costs because removal of tape frequently results in new erosions. Nonstick dressings, tube gauze, and rolled bandages are very helpful in correctly dressing affected patients.
Corticosteroid complications
The impact of the use of steroids in the treatment of AIBD becomes apparent with examination of mortality data. Mortality rates have radically decreased from 60% to 90% in the presteroid era before the 1950s to 5% to 15% since the inception of steroid use. Corticosteroids should be initiated at a high enough dose to control disease (eg, 1 mg/kg/d for pemphigus vulgaris) and tapered slowly over several months when most or all lesions have healed. When doses higher than 30 mg/d of prednisone are given, dividing the dose into a morning and lunchtime or evening dose can reduce some of the side effects. The downside to this therapy is that long-term use for more than a month is associated with side effects that require monitoring and treatment. The team approach, in which a dermatologist and a primary care physician work together to manage such patients, helps to minimize steroid-related side effects. Multiple side effects may occur with the use of chronic steroids, and dermatologists must be aware of these side effects to prevent complications.
Immune system suppression may lead to bacterial, fungal, viral, and yeast infections and reactivation of tuberculosis. Topical antibiotics such as mupirocin may limit the development of secondary bacterial infections on eroded skin. Obtaining serology of viral diseases and administering vaccines when indicated helps to prevent severe infection with varicella, zoster, hepatitis, and others. Identification of those at risk of reactivation of tuberculosis is accomplished by tuberculin skin tests and chest radiography, with chemoprophylaxis given to all tuberculin-positive patients.
Diabetes, common in patients who take long-term steroids and gain weight, should be screened for regularly in patients with AIBD through fasting blood glucose testing as well as monitoring of hemoglobin A 1C levels. Development of diabetes mellitus often requires temporary treatment with hypoglycemic agents, and when control of blood glucose levels is difficult the patient may require insulin. Patients with preexisting diabetes may require increased treatment intensity because control of blood glucose levels is likely to worsen.
Corticosteroids have also been linked to an increased risk of cardiovascular disease. High doses are particularly associated with heart failure and ischemic heart disease. The evidence for a higher risk of cerebrovascular events is not as strong.
Use of corticosteroids can cause other metabolic abnormalities, including weight gain and a cushingoid appearance, including moon face, buffalo hump, and central obesity ( Figs. 1 and 2 ). Although these changes are difficult to avoid, careful counseling at the outset can help patients in making sure they are eating a healthy diet and getting regular exercise to minimize obesity. Fluid and electrolyte imbalance occurs in the form of sodium and water retention, which may result in the development of hypokalemic alkalosis, hypertension, and lower extremity edema. Patients should be advised to consume a low-sodium potassium-rich diet. Monitoring blood pressure and initiation of potassium-sparing diuretics, if necessary, can help prevent the complications of hypertension. The use of support hose aids in reducing lower extremity edema.
Osteoporosis may occur in patients on more than 10 mg/d of prednisone, especially postmenopausal women. Bone densitometry testing using dual energy x-ray absorptiometry and treatment with bisphosphonates aid in the reduction of osteoporosis and bone fractures. Concomitant supplementation with calcium, vitamin D, and estrogen must also be considered. Additional measures to consider include weight-bearing exercise, smoking cessation, and avoiding excess alcohol intake. Risk of avascular necrosis of the femur or humerus increases with increased dose of steroids and duration of treatment. Early detection using magnetic resonance imaging is critical in preventing total destruction of a joint. Menstrual irregularities and amenorrhea can occur, and female patients should be made aware of these possibilities.
Gastrointestinal (GI) side effects include peptic ulcer disease and GI bleeding. To prevent ulcers, patients should be advised to take steroids after a meal and prescribed enteric-coated corticosteroids when available. Other preventive and treatment options include proton pump inhibitors, H 2 blockers, and sucralfate. Routine blood tests for anemia and stool tests for occult blood may detect early cases of GI bleeding. Because nonsteroidal antiinflammatory agents can increase the risk of steroid-related peptic ulcer disease, clinicians should use caution when prescribing these medications together.
Exacerbation or development of psychiatric problems can occur with the use of corticosteroids. Previously mentally stable patients may develop mood swings, euphoria, depression, psychosis, suicidal thoughts, and insomnia, which can be very disconcerting to family members. These behavioral changes may occur within 2 weeks of beginning treatment and usually respond to tapering within 3 weeks. Again, counseling patients and their families about these potential side effects and using the assistance of their primary care provider when they develop are helpful in managing such patients.
Cutaneous changes from steroids include easy bruising, thin torn skin, acne, folliculitis, striae, and/or increased growth of unwanted body hair. Meticulously avoiding trauma may limit bruising and thin torn skin, which is also prevented by the use of emollients. Acne and folliculitis may improve with topical or systemic antibiotics. Hypertrichosis can be managed by several methods, including depilation, epilation, or photoepilation, depending on patient preference.
It is obvious from the earlier discussion that a thorough history of the present illness, interim medical and surgical history, and full review of systems must be done at each visit for patients with AIBD on corticosteroids. Obtaining vital signs and performing a physical examination are also important. The dermatologist may be the first health care provider to detect an abnormality from interviewing or examining a patient, ultimately leading to the diagnosis of a complication from steroids.
Related posts:
Autoimmune Blistering Diseases Part II—Diagnosis and Management
Rituximab and its Use in Autoimmune Bullous Disorders
Pemphigoid Gestationis: Current Management
Management of Linear IgA Disease
Management of Autoimmune Bullous Diseases in France: A Nationwide Network of 30 Centers
Treatment of Chronic Bullous Disease of Childhood
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
