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* From the Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania, and Philadelphia Veterans’ Affairs Medical Center, Philadelphia, PA.
Correspondence to: Mitchell L. Margolis, MD, Pulmonary Section, Philadelphia Veterans’ Affairs Medical Center, University and Woodland Ave, Philadelphia, PA 19104; e-mail: Mitchell.Margolis{at}med.va.gov
A 35-year-old African-American man presented with cough and mild dyspnea on exertion over 3 to 4 years. His sister was known to have sarcoidosis. Physical examination revealed a slight man with mild clubbing. The chest radiograph (Fig 1 ) and chest CT scan (Fig 2 ) both demonstrated bilateral diffuse nodular interstitial and alveolar infiltrates, mediastinal and hilar lymphadenopathy, and upper-lobe fibrobullous changes consistent with sarcoidosis. A presumptive diagnosis of sarcoidosis was made; additional evaluation revealed cutaneous anergy, serum angiotensin-converting enzyme level of 108 IU (normal, 8 to 52 IU), chronic uveitis, and marked restriction on pulmonary function testing. No treatment was undertaken at this time.
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What therapy should be instituted?
Answers: Esophageal compression by enlarged lymph nodes and esophageal neuromuscular dysfunction, both due to sarcoidosis. The first-line therapy is systemic corticosteroids.
Discussion
Involvement of the gut by sarcoidosis is rare. However, case reports document a wide variety of clinical presentations of esophageal, gastric, and small and large intestinal sarcoidosis, which are discussed below. A potential confounding problem is the finding of draining lymph nodes demonstrating noncaseating granulomas in cases of gut malignancies. Therefore, in the setting of a GI mass or other endoscopic abnormality, lymph nodes demonstrating noncaseating granulomas are not adequate to make a diagnosis of sarcoidosis. Direct examination of tissue from the GI abnormality is required.
Esophageal Sarcoidosis
Reported manifestations of esophageal sarcoidosis include motility disorders, mass lesions, Barrett-like lesions, and strictures. Patients typically present clinically with dysphagia with a variety of underlying anatomic and physiologic abnormalities. These include narrowing of the pharyngoesophageal junction, compression by enlarged paraesophageal lymph nodes, abnormal motility due to nerve involvement, and strictures in the setting of granulomatous inflammation of the esophageal mucosa. While the pathophysiologic link between sarcoidosis and achalasia is less clear, several cases have been reported in which the two have been found concomitantly.
Treatment of esophageal sarcoidosis is similar to other sites of involvement, with first-line therapy consisting of systemic corticosteroids. In most of the reported cases, this therapy was successful. However, in a few instances, surgical interventions such as myotomies or stricture resections have been performed.
Gastric Sarcoidosis
The stomach is the most common site of gut involvement by sarcoidosis, with prevalence estimated as high as 10%, although symptomatic GI disease is reported to occur in < 1% of sarcoidosis patients. Patients may present with epigastric pain, nausea, vomiting, weight loss, or even hemorrhage. Radiographic and endoscopic examinations have demonstrated a wide range of findings, including gastritis, nodular mucosal changes, ulcers, a linitis plastica appearance, and polyps. Definitive diagnosis requires gastric biopsy, even in patients with known sarcoidosis. Treatment with corticosteroids or other immunosuppressives is indicated for symptomatic relief. Surgical intervention has also been reported for such complicating features as gastric outlet obstruction, suspicion of malignancy, and hemorrhage.
Another entity, idiopathic granulomatous gastritis or gastroenteritis, is distinguished from sarcoidosis by the absence of pulmonary or other organ involvement. This distinction may be one without a true difference. For example, in one case of biopsy-confirmed gastric sarcoidosis with a normal chest radiograph and chest CT scan, BAL lymphocytosis and noncaseating granulomas on transbronchial biopsy were demonstrated. Thus, even in an individual without radiographic evidence of pulmonary sarcoidosis, the disease was clearly present in the lungs. Another case suggesting that these entities are the same disorder is that of a woman found at autopsy to have granulomatous inflammation only in her stomach, despite biopsy evidence 10 years earlier of pulmonary sarcoidosis.
Intestinal Sarcoidosis
Clinical presentations of intestinal sarcoidosis are nonspecific and may include diarrhea, abdominal pain, weight loss, or protein-losing enteropathy. Local inflammation or extrinsic compression may also cause symptoms of intestinal obstruction. Nearly all of these reported cases responded to treatment with systemic corticosteroids. Rare cases of hemorrhage requiring surgical intervention, colonic polyposis, and appendicitis have also been reported.
One of the challenging features of intestinal sarcoidosis is the potential difficulty of establishing diagnostic clarity in the face of other diseases such as Crohn disease, celiac disease, and Whipple disease, which may demonstrate similar clinical and/or histologic features. Another diagnostic consideration, tuberculous enteritis, may be distinguished from sarcoidosis by biopsy evidence of caseating granulomas that are acid-fast stain or culture positive in 80% of cases.
The possibility that Crohn disease and sarcoidosis represent two manifestations of a single disorder is suggested by several case reports of individual patients who have both diseases, or have one of the two diseases diagnosed based on initial presentation, only to have the diagnosis changed based on later clinical developments. In addition, at least one study suggests that increased intestinal permeability, similar to that seen in Crohn disease, occurs commonly in patients with pulmonary sarcoidosis.
Celiac disease has also been associated clinically with sarcoidosis. A study evaluating an unselected group of sarcoidosis patients found that approximately 40% had circulating anti-gliadin antibodies. In addition, in a subset both with and without antibodies, biopsy results demonstrated an activated cell-mediated immune response in the small intestine, similar to celiac disease. This suggests that systemic activation of the mucosal immune system or anti-gliadin antibodies may play a role in the pathogenesis of sarcoidosis with a causative dietary antigen.
Finally, some clinical overlap has been observed between sarcoidosis and Whipple disease. Early features of the two diseases may be similar, including nonspecific symptoms such as fevers and arthralgias. Several reports document patients with initial biopsy results demonstrating granulomas consistent with sarcoidosis, who were subsequently found to have Whipple disease. In one report, the initial pulmonary presentation was postulated to represent a sarcoid reaction to underlying Whipple disease. While immunologic similarities between the two diseases have been noted (cutaneous anergy, decreased circulating T-lymphocytes), the pathophysiologic significance of the observed clinical overlap is unknown.
Our patient was treated with prednisone at 30 mg/d and had a G-tube placed for nutrition. His dysphagia completely resolved. Three months after starting prednisone, he was eating normally and the G-tube was removed.
Clinical Pearls
Footnotes
This work was performed at the Philadelphia Veterans’ Affairs Medical Center.
This work was supported by the Parker B. Francis Fellowship.
As of April 17, 2006, Dr. Wasfi will be a full-time employee of Merck Research Laboratories.
None of the authors are involved in any organization with a direct financial interest in the subject of this article.
Received for publication April 11, 2006. Accepted for publication June 22, 2006.
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