The number of patients, who undergo stem cell transplantation (SCT) from various stem cell sources, increases every year. By the end of 2008, a total of 1708 transplant procedures have been performed with 83% (1417) being first-time transplants and the rest (17%, 291) are repeated transplants mostly for relapsed patients.⁶ Chronic graft-versus-host disease (cGVHD) is still a major cause of morbidity and mortality after SCT and is caused by an immunological reaction against antigens in the SCT recipient by the immune competent donor graft. It occurs in 30 - 70% of recipients who survived beyond 100 days following transplantation, and it is dependent on the degree of human leukocyte antigen (HLA) mismatch with the donor and the source of the stem cells. It is also responsible for the death of 12% to 20% of graft recipients.^{1, 7-9}

The main target organs of chronic GVHD are skin, eyes, mouth, liver, esophagus, bowel, lung and serosa; and the manifestations of cGVHD have features resembling auto immune and other immunological disorders such as scleroderma, Sjogren’s syndrome, keratoconjunctivitis, buccomucositis, primary biliary cirrhosis, wasting syndrome, pulmonary insufficiency, bronchiolitis obliterans (BO), immune cytopenias and chronic immune deficiency.^9,10 Patients with cGVHD have decreased performance status, impaired quality of life (QOL) and an increased risk of mortality.

Muscle-related complications, fasciitis and myositis, are rare cGVHD manifestations, and their clinical features resemble autoimmune eosinophilic fasciitis and idiopathic polymyositis.^11-14 Muscle cramps are a common complaint, although the pathophysiology is not understood. Myositis, with tender muscles and elevated muscle enzymes, may start as a proximal myopathy but it is rare. The common clinical symptoms of myositis are moderate-to-severe proximal muscle weakness, myalgia, fever, contractures and skin indurations occur over the areas of muscle involvement. The majority of patients present with elevated creatinine phosphokinase enzymes.

The new cGVHD diagnostic guidelines proposed fasciitis as diagnostic, and myositis as a distinctive sign and symptom of cGVHD manifestation.⁵ Patients with fasciitis develop skin swelling, and thereafter the skin becomes taut, bound down to the underlying tissue, and irregularly thickened; and thereafter demonstrating multiple small depressed areas, giving rise to ‘peau d’ orange’ appearance. Contractures and joint stiffness are also observed. Muscle biopsy in cGVHD myositis usually demonstrates non-specific changes, such as degeneration, necrosis and regeneration of muscle fibers and infiltrates of inflammatory cells. En-bloc biopsy, with sampling of both muscle and fascia, can give more definite diagnosis. The pathological findings of fasciitis include lymphocytic infiltration in edematous fascia and a subsequent increase of collagen fibers. The infiltration is diffuse and it often extends from the fascia into the interstitium of the muscles.

Magnetic resonance imaging (MRI) is useful in SCT recipient presented with weakness, decreased range of movement, contracture or other symptoms and signs suggestive of chronic graft-versus-host disease-related myositis and fasciitis; and it can effectively confirm the affected muscles or muscle groups. MRI can be helpful for diagnosis and management in determining the depth of soft-tissue involvement, particularly within fasciae and muscles, which is related to the severity of the disease. MRI can determine the best site for biopsy and also monitor therapeutic response.¹⁵ Abnormal T2 prolongation in muscle fibers is a constant MRI finding of myositis. In a retrospective study of 16 patients by Horger et al., MRI showed musculocutaneous abnormalities reflecting different degrees of inflammation and collagen tissue involvement of the skin, subcutaneous fat tissue, muscle fasciae, subfascial muscular septae, or findings compatible with myositis.^15-17 The most frequently involved muscle fasciae comprised those of the vastus lateralis muscle, biceps femoris muscle, gastrocnemius medialis muscle, serratus anterior muscle, and latissimus dorsi muscle.^15,17 Increased signal of involved tissues on STIR-images and fat-saturated post-gadolinium T1-weighted images represented the most frequent MR-signal abnormalities.¹⁷ Fatty infiltration and wasting are also seen in the affected muscle bulk in chronic cases. Increased fluid signal along fascial planes and fascial enhancement, on the other hand, are features of fasciitis. Although different in degree and extent, the thickness and hyperintensity of the involved fascia and the infiltration of subcutaneous septa and muscles are well suited for visualization with MRI.¹⁷ In general, there was good concordance between clinical and MRI findings.

It is not mandatory for making a diagnosis of fasciitis or myositis; however, these two diagnoses carry different prognoses. The cases of almost all patients with fasciitis or myositis were complicated with other manifestations of chronic GVHD, but there were different tendencies regarding the involved organs among the patients with fasciitis and myositis. In patients with fasciitis, lung disease (BO) and sicca syndrome were more frequent than oral and skin involvement. Pulmonary complications will affect the patient’s prognosis, because they can cause severe respiratory failure. Hence, the fact that patients with fasciitis tend to have pulmonary complications may be related to their poor prognosis. It is rare for myositis patients to develop respiratory failure, and therefore they usually have better prognosis than fasciitis patients.

Due to the similarities in their clinical manifestations, autoimmune eosinophilic fasciitis and idiopathic polymyositis are both differential diagnoses of cGVHD-related myositis and fasciitis. In eosinophilic fasciitis, MRI reveals characteristic findings including thickening, signal abnormalities, and contrast enhancement of the superficial and, to a lesser extent, deep muscle fasciae.¹⁸ The preferential involvement of fasciae and superficial structures before involvement of muscles in eosinophilic fasciitis aids differentiation from cGVHD-related myositis and fasciitis. On the other hand, MRI findings in idiopathic polymyositis are similar to those in cGVHD-related myositis and fasciitis; diagnosis may rely on histopathological diagnosis and clinical history. MRI can yield accurate information about the extent of muscle involvement and guide muscle biopsy.

Both fasciitis and myositis caused by chronic GVHD can result in disabilities that reduce the patient’s QOL. Since the treatment response for myositis is good, an early diagnosis by MRI; biopsy, which includes fascia and muscle; and prompt treatment are important to prevent impairment of the patient’s QOL with persistent disability. Furthermore, once muscle atrophy occurs, it has been suggested that the muscle may not recover despite increased immune suppression and control of the inflammatory process. For this reason, a high clinical index of suspicion is needed for accurate diagnosis so that early diagnosis and prompt treatment for fasciitis and myositis can be offered to prevent or curb further progression of the complications. An early MRI should be arranged in SCT or BMT patients, who present with muscle cramps, myalgia, and weakness etc. musculoskeletal symptoms, to diagnose the condition early and guide biopsy.

The muscle-related complications of fasciitis and myositis, caused by chronic graft-versus-host disease (cGVHD) after stem cell transplant (SCT) are rare, but at times will severely impair a patient’s quality of life (QOL). MRI is useful for establishing the diagnosis, guiding the choice of biopsy site, and assessing treatment response. As the treatment response for myositis is fairly effective, an early diagnosis by magnetic resonance imaging (MRI) and biopsy, which includes fascia and muscle; and prompt treatment are important and crucial to prevent the impairment of the patient’s QOL with persistent disability.