Pneumatosis Intestinalis Associated with Juvenile Dermatomyositis

We herein report a case of pneumatosis intestinalis (PI), a condition characterized by the presence of gas within the wall of the digestive tract, associated with juvenile dermatomyositis (JDM). A 16-year-old girl, diagnosed with JDM at the age of 10, presented with abdominal pain and distention. She developed PI based on radiological findings that also included a dilated large intestine, extraluminal gas, and secondary diaphragmatic elevation. She was observed with medical therapy including bowel rest and hyperbaric oxygen therapy. However, she ultimately developed a strangulated obstruction 5 years after presentation with PI and large intestine resection and colostomy were performed emergently.


Introduction
Juvenile dermatomyositis (JDM) is an autoimmune vasculopathy of uncertain origin involving multiple organ systems. It is defined as chronic inflammation of the striated muscle and skin [1,2]. Classic JDM presents with an insidious progression of malaise, fatigue, muscle weakness, fever, and a rash that may predate diagnosis by three to six months. In more than three-fourths of the children with JDM [3], the cutaneous abnormalities are pathognomonic of the disease at presentation. The most typical cutaneous manifestations are heliotrope discoloration of the upper eyelids and Gottron papules more frequently in young children. In cases with severe skin vasculopathy, cutaneous ulcers present in 5% to 10% of patients [4,5].
Gastrointestinal manifestations may also be present as extra-muscular symptoms in JDM. Vasculopathy in the mucosa of the gastrointestinal tract with resulting tissue ischemia or an acute mesenteric infarction can occur [6].
Pneumatosis intestinalis (PI), first described in 1754, is a rare condition characterized by gas bubbles within the wall of the digestive tract. It has been associated with medical conditions including gastrointestinal and chronic pulmonary diseases [7]. However, it rarely occurs with autoimmune disorders. Among several PI cases associated with JDM, their gastrointestinal severity varies from benign to lifethreatening causes [8]. We experienced a case of JDM complicated by PI eventually requiring a colostomy.

Case Presentation
In 1998, a girl presented with facial erythema and Gottron's papules at 10 years of age and visited the Department of Dermatology at Tokyo Women's Medical University. Muscle weakness and elevation of muscle-derived enzymes (creatine kinase 1105 IU/L, aldolase 30.9 IU/L, and myoglobin 470 ng/mL) developed during the following year. She was diagnosed as having JDM on clinical and pathological grounds after skin and muscle biopsy. Muscle biopsy revealed perivascular mononuclear inflammatory infiltrate, arterial wall thickening, and perifascicular atrophy. Anti-Jo-1 antibody was negative. Oral prednisolone (PSL, 60 mg/day, 2 mg/kg) alleviated the clinical symptoms and laboratory findings. Following a decrease in the dosage of PSL, myositis and skin erythema developed at age 14. The myositis remained stable whereas the skin rash intermittently progressed. She presented with abdominal pain and severe distention when the dosage of PSL was decreased to 9 mg/day in 2004, at the age of 16. She was afebrile. Radiological examination demonstrated pneumatosis, a dilated large intestine, and dominance of air in the abdominal cavity suggesting the bowel-wall air above the colon (Figures 1(a) and 1(b)). She was not able to lie down on her back and developed respiratory distress because of the marked abdominal distention and secondary diaphragmatic elevation. She was diagnosed with PI and treated medically with bowel rest and hyperbaric oxygen therapy. She partially improved but abdominal pain and distention persisted, sometimes got a little better but then got worse again, and finally developed large bowel obstruction with strangulation in 2009 necessitating emergent large and small bowel resection with a double barrel colostomy. Further exploration revealed foci of necrosis with several perforations in both large and small intestines. Since the colostomy was performed, she was then receiving nutrition parenterally and has been free from abdominal pain with less distention without hyperbaric oxygen therapy during 6 years after the resection. Her steroids were changed from oral PSL to intravenous betamethasone at a dosage of 0.3 to 0.9 mg/day depending on skin manifestations but not on abdominal symptoms. In February 2015, anti-aminoacyl-tRNA synthetase antibodies were not detected and the patient was diagnosed with severe osteoporosis (% of young adult mean bone marrow density between lumbar vertebrae L2-L4: 53%), presumably caused by long term administration of betamethasone. She was then partially switched back to oral PSL. The dosage of PSL has been controlled based on gastrointestinal and skin manifestations and is currently maintained at 10 mg daily.

Discussion
We reported a case of PI associated with JDM eventually requiring large bowel resection and colostomy. PI is not a diagnosis but rather a physical or radiographic finding, usually as a result of a pathologic process. Impaired mucosal integrity, increased intraluminal pressure, bacterial flora, and intraluminal gas during illness all can lead to the presence of gas within the wall of the gastrointestinal tract [9].
Among autoimmune disorders, PI is commonly noted in systemic sclerosis but rarely associated with dermatomyositis or JDM. Previously, 8 cases of PI in JDM have been reported in the literature (Table 1). Two patients died of intestinal perforation and subsequent sepsis [10,11]. The time required to normalization of gastrointestinal conditions varied from a week to over a year in those patients that survived. This patient had 5 years from the time of first manifestations of PI until the development of a strangulated obstruction and was never fully healthy during that time. Intestinal resection and colostomy were thought to be unavoidable.
In the JDM cases that developed PI, skin manifestations were more common than myositis. Two of the 8 cases had skin ulceration. The pathogenesis of PI in JDM is not clear. However, some authors have speculated that gastrointestinal ischemia secondary to vasculopathy could result in loss of integrity of the mucosa and bacterial production of gas with submucosal dissection of intraluminal gas [12]. The high frequency of skin manifestations and ulcers might suggest that skin vasculitis has a correlation with vasculopathy in the mucosa of the gastrointestinal tract. Interestingly, severity and prognosis of PI associated with JDM vary though the number of reported patients was small. Benign cases were diagnosed by routine X-ray finding without abdominal manifestations and resolved in natural course; however, there were fatal cases complicated with intestinal perforation, subsequent infection, and sepsis [ Table 1]. The difference of the prognosis of PI is unclear but can be affected by severity of vessel vasculopathy, initial treatment, and myositis specific/associated antibodies.
Immunosuppressive treatments including glucocorticoids seemed to be effective in some of the reported cases and these were able to suppress the vasculopathy in the early phase of PI. In addition, they could help to cause the submucosal lymphoid tissue atrophy and subsequent dissection of air into the bowel wall that occurs. However, once peritonitis and sepsis occur, the problem is surgical. Considering the fact that  Case Reports in Rheumatology most of the cases were reported before 2000, early diagnosis and timely initiation of immunosuppressive therapy may help to prevent vasculopathy and the development of PI. PI should be considered on the differential diagnosis in patients with JDM presenting with abdominal complaints, especially in patients with severe skin vasculitis.