**15. Myopathy**

GCs have direct catabolic effects on skeletal muscles. These catabolic effects are mediated by several cellular mechanisms. GCs inhibit the glucose uptake in skeletal muscles, by this way stimulate protein catabolism and inhibit protein synthesis in muscles. These direct effects causes muscle weakness. Besides, it was shown that GCs increase the transcription of genes encoding components of the ubiquitin-proteasome pathway, thereby increasing the proteolytic capacity of muscle cells. Transactivation of certain genes through glucocorticoid receptors also contributes to muscle atrophy. GCs inhibit the production by the muscle of IGF-I, a growth factor that stimulates the development of muscle mass by increasing protein synthesis and myogenesis, while decreasing proteolysis and apoptosis. In addition, GCs stimulate the production of myostatin, a growth factor that inhibits the muscle mass development by downregulating the proliferation and protein synthesis [132–135].

Myopathy usually develops over several weeks to months with the use of GCs. The typical clinical features are proximal muscle weakness and atrophy in both the upper and lower

### **Monocytes/macrophages**

• Reversible monocytopenia (>40% reduction)

extremities. Quadriceps and other pelvic girdle muscles are more severely affected. Myalgias and muscle tenderness are not seen. Although there is some variation in the dose and duration of GCs prior to the onset of muscle weakness, the higher the dose of GCs used related with the more rapid the onset. But it is more common in patients treated with ≥10 mg/day of prednisone or equivalent. The severity and the mechanism for the catabolic effect of GCs may differ with age. Creatine phosphokinase, aldolase, aspartate aminotransferase, lactate dehydrogenase (LDH), LDH isoenzymes, and changes in urinary excretion of creatine neither correlate with the degree of muscle weakness, nor discriminate between patients receiving small and large doses of GCs. So there is no definitive diagnostic test for myopathy induced by GCs. Diagnosis is to exclude other possible etiologic factors. Weakness of peripheral and respiratory muscles may have significant clinical effects, such as loss of quality of life, fatigue, impaired wound healing, compromised lung function, and poor immune response. Treatment is discontinuation of GCs or dose reductions immediately. Symptoms generally improve within 3–4 weeks

Side Effects of Glucocorticoids

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http://dx.doi.org/10.5772/intechopen.72019

The most important cutaneous side effects of systemic GCs are skin atrophy-fragility, irreversible striae rubrae distensae (red striae), purpura, and delayed wound healing. A rare but unimportant side effect is hypertrichosis. Fortunately, hypertrichosis is usually reversible and disappears after discontinuation of GCs. The potency and duration of therapy determine the

All parts of the skin involved become thin and fragile. Women seem to be more susceptible to this side effect. Suppression of cutaneous cell proliferation and protein synthesis causes skin atrophy. Further effects of GCs on the skin are a decreased synthesis of epidermal lipids, as

These are visible linear scars that form in areas of dermal damage, presumably during mechanical stress. Stria means scar tissue. For this reason, once developed, they are permanent. In the

The effects of GCs on wound healing are multifactorial. GCs prevent the early inflammatory phase, which is essential for wound repair. GCs also affect keratinocytes (epidermal atrophy and delayed reepithelialization), fibroblasts (reduced collagen and ground substance, resulting in dermal atrophy, and striae), and vascular connective tissue support (telangiectasia, purpura, and easy bruising). According to delayed granulation, tissue formation of GCs impairs angiogenesis. Furthermore GCs have impact on wound healing by the regulation of pro-inflammatory cytokines, growth factors, matrix proteins, and matrix proteases [142].

differential diagnosis, excessive weight gain and pregnancy should be excluded [141].

of dose reductions, and often resolve after discontinuation of GCs [136–138].

**16. Cutaneous side effects**

**16.1. Skin atrophy**

**16.2. Striae**

**16.3. Delayed wound healing**

occurrence and severity of cutaneous lesions.

well as an increased transepidermal water loss [139, 140].


### **Other immune effector cells**


extremities. Quadriceps and other pelvic girdle muscles are more severely affected. Myalgias and muscle tenderness are not seen. Although there is some variation in the dose and duration of GCs prior to the onset of muscle weakness, the higher the dose of GCs used related with the more rapid the onset. But it is more common in patients treated with ≥10 mg/day of prednisone or equivalent. The severity and the mechanism for the catabolic effect of GCs may differ with age. Creatine phosphokinase, aldolase, aspartate aminotransferase, lactate dehydrogenase (LDH), LDH isoenzymes, and changes in urinary excretion of creatine neither correlate with the degree of muscle weakness, nor discriminate between patients receiving small and large doses of GCs. So there is no definitive diagnostic test for myopathy induced by GCs. Diagnosis is to exclude other possible etiologic factors. Weakness of peripheral and respiratory muscles may have significant clinical effects, such as loss of quality of life, fatigue, impaired wound healing, compromised lung function, and poor immune response. Treatment is discontinuation of GCs or dose reductions immediately. Symptoms generally improve within 3–4 weeks of dose reductions, and often resolve after discontinuation of GCs [136–138].
