Malakoplakia (ORPHA:556)
Malakoplakia is a chronic multisystem granulomatous inflammatory disease characterized by the presence of single or multiple soft plaques on various organs of the body.
Epidemiology
Prevalence is unknown but more than 700 cases have been described in the literature.
Clinical description
Malakoplakia can occur in all ages, with a mean age at diagnosis of 50 years old and a female predominance. Pediatric cases are rare. It is most common in immunodeficient patients with a history of diabetes, transplantation, lymphoma, steroid therapy or alcoholism. In the majority of cases (60-80%), malakoplakia affects the urinary tract (bladder, kidney, and ureters) and cases of locoregional extension have been reported (retroperitoneal region and lymph nodes). Other organs can also be involved, with the gastrointestinal system (left colon, sigmoid, rectum, stomach) being the second most common site (15%). Other sites include the genital tract, skin, neck, tongue, lungs, and central nervous system. Patients are either asymptomatic or present with clinical symptoms that are non specific (fever, pain) and that vary depending on the organ involved. In case of urinary tract involvement, patients generally present with chronic urinary tract infections and symptoms such as urinary urgency, hesitancy, intermittent dysuria, hematuria, and proteinuria. In case of gastrointestinal involvement, patients can present with symptoms such as recurrent diarrhea, dyspepsia, abdominal pain, and hemorrhage. In case of malakoplakia of the female genital tract, patients usually present with vaginal bleeding. Cutaneous malakoplakia presents as papules or ulcerations on various locations (abdomen, face, perianal region) associated with rash and itching. Malakoplakia can also be associated with other granulomatous diseases such as sarcoidosis and tuberculosis, and with carcinomas (prostate and colorectal carcinomas).
Etiology
Malakoplakia seems to be due to an impaired response to bacterial infection. Macrophages and monocytes show a defective phagolysosomal activity: they phagocytose bacteria but are unable to digest them completely. Partially digested bacteria accumulate in the cytoplasm and lead to a granulomatous reaction of the immune cells. It has been suggested that the defective phagolysosomal activity could be due to a decrease in the concentration of intracellular cyclic guanosine monophosphate (cGMP).
Diagnostic methods
The diagnosis of malakoplakia is difficult due to the absence of specific clinical symptoms and no specific characterization in imaging. Diagnosis is based on endoscopy which reveals the presence of vascularized yellowish or white polypoid nodules or plaques. The diagnosis is confirmed by biopsy of the affected tissue. Histological examination reveals the presence of von Hansemann cells (histiocytes with small nuclei and granular acidophilic cytoplasm) with Michaelis-Gutmann bodies (periodic acid-Schiff and von Kossa positive calcific inclusions). This lesion is pathognomonic for malakoplakia. Michaelis-Gutmann bodies probably correspond to partially digested calcified bacterial inclusions.
Differential diagnosis
Depending on the organ involved, differential diagnoses include primary or metastatic malignancies, inflammatory diseases (sarcoidosis, Crohn's disease; see these terms), infections (tuberculosis, Whipple disease; see these terms), and cutaneous fungal infections.
Management and treatment
Treatment consists in antibiotherapy that uses intracellular molecules (fluoroquinolones, trimethroprim-sulfametoxazol). Currently, the duration of therapy is still not standardized. In pseudo-tumoral cases, surgical removal of the lesions is required.
Prognosis
Prognosis is usually good. However, recurrences and complications may occur over the years such as renal failure in case of urinary tract involvement.

                            Last update: 
                            August 2011


                            - Expert reviewer(s): 
                            Dr Maïté DAROUX