The gastrointestinal tract is the second most common site of involvement by malakoplakia, and most of those cases involve the colon and the rectum (11
). Malakoplakia of the colon has a distinctive gross and microscopic appearance. Colonic involvement can be either segmental or diffuse. In the early stages, the lesions appear soft, flat and tan-coloured. Later, they can develop into raised, tan-grey and hyperemic lesions (10
). Histologically, malakoplakia is characterized by aggregates of large histiocytes (known as von Hansemann cells) with intracellular and extracellular inclusions (known as Michaelis-Gutmann bodies), which are phagolysosomes that have become encrusted with calcium and iron salts. These findings are pathognomonic and establish the diagnosis of malakoplakia.
The etiology of malakoplakia is still not fully understood, but there is an association with Gram-negative bacterial infections, particularly with Escherichia coli. The likely mechanism of malakoplakia is defective lysosomal processing of micro-organisms by macrophages in the accumulation of debris in lysosomes and subsequent mineralization.
Another potential contributing factor to the development of malakoplakia is an impaired immune response (eg, immunosuppression used to prevent rejection in organ transplant patients). In a review by Long and Althausen (12
), approximately 40% of malakoplakia cases that did not involve the urinary tract were associated with immunosuppression. In a review of the literature, there have been three cases (8
) of malakoplakia in liver transplant recipients. Two of those case reports (9
) involved the gastrointestinal tract (the small bowel and mesentery, and the sigmoid colon). The indications for transplantation included hepatitis C infection and hepatocellular carcinoma. The clinical presentation of malakoplakia included small bowel obstruction and chronic diarrhea. No coexisting infection was reported, although the patient described by Rull et al (8
) died four weeks after a laparotomy for bowel obstruction secondary to pneumonia that was caused by Pseudomonas
species. In the patient described in the present paper, the degree of immunosuppression was relatively mild, consisting of tacrolimus monotherapy with low trough drug levels. Perhaps her decompensated liver disease contributed to her susceptibility to malakoplakia. There have been no reports of tacrolimus directly inducing lysosomal dysfunction or malakoplakia.
Attempts at treatment of malakoplakia have included two main approaches: the administration of a cholinergic agonist to improve macrophage function, and antibiotic therapy. Abdou et al (13
) reported a patient with rectal and retroperitoneal malakoplakia. They documented that the patient had monocytes that had decreased bactericidal activity against E coli
, abnormally large lysosomal granules, low levels of cyclic GMP in mononuclear cells and poor release of beta-glucuronidase in a bactericidal assay (13
). Low levels of cyclic GMP in cultured malakoplakia cells were corrected by treatment with carbachol, a cholinergic agonist. The patient’s clinical course improved after oral treatment with bethanechol chloride. The rationale for antibiotic therapy is to administer antibiotics that concentrate in macrophages. van Furth et al (14
) reported two patients with malakoplakia who were treated with ciprofloxacin and experienced regression of their lesions with long-term therapy. Yousif et al (15
) also reported a case of rectal malakoplakia that was successfully treated with a six-month course of ciprofloxacin, along with a reduction of immunosuppression (15