MSK MANIFESTATION

• Sclerotic-type chronic GVHD (ScGVHD) of the skin encompasses several cutaneous presentations characterized by inflammation and progressive fibrosis of the dermis and subcutaneous tissues, resembling morphea, systemic sclerosis, or eosinophilic fasciitis [13, 14].
• One of the other distinctive feature for chronic GVHD is depigmentation [3].

• Muscle loss, most frequently a result of disuse, deconditioning, or side effects of immunosuppressive treatment, particularly corticosteroids. [5]. This can lead to strength and muscle mass decreases at a rate of about 1% per day [15]. 
• The weight bearing lower extremities and low back extensor muscles are more affected than upper extremities, making it difficult to begin ambulating after prolonged periods of rest [15]. 
• Prolonged immobility and nutrient deficiency, in concert with paraspinal muscle atrophy, can contribute to debilitating back pain [16]. 

Steroid-induced Myopathy:  

• Acute - typically occurs within 1 week of high-dose oral corticosteroid use and can be associated with rhabdomyolysis and pain. 
• Chronic form occurs weeks to months into prolonged, high-dose steroid administration  The patients experiences general painless muscle weakness in the upper and lower extremities and the neck and usually reports finding it difficult to rise from a seated position or lifting up utensils to eat [17]. 

As many as 50% of patients who undergo HSCT develop osteopenia or osteoporosis, and cGVHD is associated with an even higher incidence [20]. This is often the result of chronic glucocorticoid use, a major risk factor for osteopenia and osteoporosis because of increased bone turnover [21]. Other risk factors that these patients face that contribute to bone density loss are: 

• Calcineurin inhibitor use, chemo and radiation therapy, gonadal dysfunction, 
• Renal dysfunction, 
• Increased marrow turnover due to hematogenous malignancy, and 
• Decreased weight-bearing activity.

The HSCT itself causes a fundamental alteration of bone mineral metabolism, with loss seen in the first 6 to 12 months [22]. Bone density loss in cGVHD is typically seen more in the femoral heads than the vertebrae, a distinction when compared with menopausal osteoporosis [20,21],  though the humeral head, knees, and ankles can also be affected [23,24].

Lastly, patients with osteoporosis can develop hip flexor contractures due to sustained forward-flexed posture. A tight iliopsoas muscle may lead to worsening lumbar lordosis, increasing pain, and adding force being applied to vertebrae already prone to fracture [25]. 

 Muscle mass and strength may be compromised because of an inflammatory myositis, mimicking polymyositis or dermatomyositis, that is a direct, immune-mediated result of cGVHD [18].   Associated with tapering of immunosuppressant medications and is associated with the same genetic markers seen in patients with this autoimmune disease who have not undergone HSCT [5]. Typically, this presents with painful, symmetric proximal weakness. 

cGVHD is associated with several possible neurologic sequelae, including mononeuropathies, generalized peripheral neuropathy, and inflammatory neuropathy. A combination of multiple neuropath. This has also been shown to cause a neuropathic process that resembles acute inflammatory demyelinating polyneuropathy (AIDP), and is thought to be a result of direct infiltration of peripheral nerves by donor T cells [6].

An EMG can be diagnostic and can show demyelination, axon loss, or both [19]. The first electromyographic sign of AIDP is an absent F-response, with subsequent findings of conduction block and denervation. 

Nerve entrapment can be either by mechanical compression or fascial inflammation. As the inflamed fascia and/or skin surrounding peripheral nerves become fibrosed, the nerve may become entrapped and damaged. 

Nerves at high risk for entrapment are those with little surrounding tissue, such as the ulnar nerve at the cubital tunnel and peroneal nerve at the fibular head. The median nerve at the carpal tunnel can also be damaged due to wrist flexion contractures.

 In rare instances, develops when tapering immunosuppressive medication because of pre-existing autoantibodies against postsynaptic acetylcholine receptors. Most commonly seen in patients who received the HSCT for aplastic anemia. Symptoms typically are progressive weakness with exertion, with recovery of strength after rest. Ptosis is a common first symptom and its presence along with generalized weakness. May warrant an EMG that includes repetitive stimulation studies and blood tests to detect antibodies to acetylcholine receptors [6].