Non-familial visceral myopathy: Clinical and pathologic features of degenerative leiomyopathy
Degenerative leiomyopathy (DL) is a distinctive form of acquired degenerative visceral myopathy of uncertain etiology that occurs largely in Africa and results in intestinal pseudo-obstruction (IP). In this review of 39 patients from the Western Cape region of South Africa, the mean age at presentation was 9.5 years (range 6 months to 16 years). Characteristic clinical features included a chronic, insidious history of repeated attacks of abdominal distension, abdominal pain, and vomiting. Marked gaseous distension with atony and IP, especially of the colon, was noted on X-ray films. Megacolon was the most common radiologic feature, but pseudo-obstruction extended proximally into the small intestine in some patients with advanced disease. In the majority of cases the condition was progressive and eventually affected the entire gastrointestinal (GI) tract. Histologic features included smooth-muscule degeneration with vacuolated cytoplasm, extracellular edema, and increased fibrosis of both muscular layers of the muscularis propria, particularly the longitudinal layer. Similar changes occasionally occurred in the muscularis mucosae and vascular walls of the involved bowel. Neuronal loss was absent, but hyperplasia of the myenteric plexus was observed in 7 cases. Electron microscopy showed atrophic, degenerative smooth-muscle cells with intervening collagen fibers. Intracellular fluid accumulation immediately adjacent to the cytoplasmic membrane was a constant finding in the less severely affected areas. Other characteristic ultrastructural findings included nuclear chromatin margination, diminished pinocytosis, and fragmentation of cytoplasmic membranes. Although specific morphologic changes of DL always primarily affected the most distal part of the GI tract, megacystis and megaureter were also noted in some patients. In addition, at postmortem examination in a few terminal cases, arterial smooth muscle was also affected in other organs and was associated with considerable fibrosis and proliferation of the intima. Immunohistochemistry revealed excessive expression of vasoactive intestinal peptide (VIP) in bowel sections from 29 of 35 cases, while unequivocal hyperplasia of the myenteric plexus occurred in 7 of the 29 cases with increased VIP expression. Patients with increased VIP expression had enlargement of the neurons of all three plexuses, associated with frequent vacuolization of the cytoplasm. There was increased expression of VIP in bowel specimens from a number of different sites in the GI tract in these patients. The lamina propria also contained positive VIP-staining neurofibrils. Within the neurons, the VIP staining was homogeneously distributed in the cytoplasm and large droplets or granules were located along individual nerve fibrils and axons. The increased expression of VIP is the opposite effect of neuronal causes of IP such as Hirschsprung's disease, and combined with study of myosin and actin is a fairly consistent marker for DL. Management was preferably conservative with a low-residue diet supported by prokinetic agents. Surgical decompression was reserved for patients not responding to conservative management in the acute phase. Surgical resection was generally not advocated, as it failed to correct the underlying intestinal problem.