Progressive muscle weakness: More there than meets the eye
Dermatomyositis-polymyositis
Dermatomyositis-polymyositis is characterized by proximal muscle weakness, creatine kinase elevation, erythema on sun-exposed skin, heliotrope rash, and Gottron papules. It occurs mostly in women after the second decade of life. Some medications have been implicated in its pathogenesis, such as statins, fibrates, hydroxyurea, penicillamine, and omeprazole (Prilosec).7
In a middle-aged patient, this diagnosis should prompt a search for cancer, especially of the gastrointestinal system, breast, and lung.8 Cancer can arise up to 3 years after the diagnosis of dermatomyositis or polymyositis.
Antisynthetase antibody syndrome is suspected if the patient is positive for antisynthetase antibody and has the following manifestations: acute onset of disease, constitutional symptoms, interstitial lung disease, inflammatory arthritis, mechanic’s hands (thickened, cracked skin on the palmar aspect of the thumb and index finger), and Raynaud phenomenon.4,8,9
The diagnosis is made by a thorough clinical evaluation. Electromyography can show an inflammatory pattern of myopathy. The gold standard test for this diagnosis is muscle biopsy.
Our patient has a normal creatine kinase level, which excludes the diagnosis of dermatomyositis-polymyositis.
Statin-induced myopathy
Up to 10% of patients taking statins develop myalgia. Rhabdomyolysis, the extreme form of myopathy, is rare.
The exact mechanism of statin-induced myopathy remains unclear; mitochondrial dysfunction, cholesterol composition of cell membranes, and coenzyme Q10 deficiency have been proposed.
Risk factors for statin-induced myopathy include female sex, older age, higher doses of statins, a family history of statin-induced myopathy, and hypothyroidism. Drugs that increase the risk include fibric acid derivatives, macrolides, and amiodarone (Cordarone). If a statin and any of the above drugs are both required, certain statins—ie, pravastatin (Pravachol) and rosuvastatin—are recommended, since they are the statins least likely to cause rhabdomyolysis.5,7,10–12
The combination of fluvastatin (Lescol) and gemfibrozil (Lopid) has also been found to be safe.13 In a crossover study in 17 patients, no significant difference was seen in the area under the curve for plasma concentration over time, in the maximum plasma concentration, or in the time to maximum concentration with the combination vs with each drug alone.13
Our patient is taking a statin and has hypothyroidism, which increases the risk of statin-induced myopathy. However, her creatine kinase level is normal.
Cushing syndrome
Cushing syndrome (hypercortisolism) is one of the most challenging endocrine diseases to diagnose. Most of its clinical features overlap with those of common diseases, and some patients have an atypical clinical presentation with only isolated symptoms. Further, its presentation can be subtle, with weight gain, amenorrhea, muscle weakness, and easy bruisability. Acne, moon facies, plethora, abdominal striae, and purpura are other common signs. It is three to 10 times more common in women than in men.
Cushing syndrome can be classified according to whether or not the excess cortisol secretion depends on corticotropin (formerly called adrenocorticotropic hormone or ACTH) (Figure 1). In corticotropin-dependent cases, the most common cause is pituitary adenoma. (When Cushing syndrome is due to excessive pituitary secretion of corticotropin, which in turn stimulates the adrenal glands to secrete excessive amounts of cortisol, it is called Cushing disease). Other causes of corticotropin-dependent Cushing syndrome are ectopic corticotropin-producing tumors such as carcinoid tumors or medullary thyroid cancers. Corticotropin-independent Cushing syndrome can be caused by adrenal adenomas, adrenal carcinoma, and bilateral primary micronodular or macronodular adrenocortical hyperplasia.14–17
However, the most common cause of Cushing syndrome is glucocorticoid therapy.
BACK TO OUR PATIENT: HER CONDITION DETERIORATES
Our patient’s physical condition deteriorates, she develops respiratory distress, and she is admitted to the medical intensive care unit. Her mental status also deteriorates, and she becomes lethargic and unresponsive.
She is intubated to protect her airway. After this, she develops hypotension that does not respond to fluid resuscitation and that requires vasopressors. Her condition continues to worsen as she develops acute kidney injury and disseminated intravascular coagulation. Her vesicular rash becomes more widespread, involving the entire trunk.
A workup for sepsis is initiated, but her initial blood and urine cultures are negative. Chest radiography does not reveal any infiltrates. No other source of an infection is found.
Varicella zoster is isolated on viral culture of a specimen obtained from the rash, and a polymerase chain reaction test of her blood shows cytomegalovirus DNA (64,092 copies per mL). Immune suppression is suspected, so a CD4 count is ordered (Table 2). Serologic tests for human immunodeficiency virus are negative.
What could have caused our patient to have muscle weakness in addition to disseminated zoster with cytomegalovirus viremia?
The diagnosis here is Cushing syndrome.
