Whipple’s disease
Whipple's disease (WD) is caused by T. whipplei bacteria and can affect the central nervous system (CNS). Symptoms vary and can include confusion, cognitive impairment, and abnormal movements. Diagnosis involves brain MRI and T. whipplei PCR on cerebrospinal fluid (CSF). Treatment includes antibiotics followed by long-term oral maintenance therapy. In some cases, corticosteroids may be needed, and patients should be monitored for immune reconstitution inflammatory syndrome (IRIS). Relapses may occur and require additional treatment.
2023-12-31 21:58:24 - Editor
Introduction to Whipple's Disease (WD)
Whipple’s disease (WD) is caused by T. whipplei, a gram-positive bacillus related to Actinomycetes. The central nervous system (CNS) is involved either as part of classic WD, CNS relapse in previously treated WD, or isolated CNS infection. Most commonly, CNS involvement is asymptomatic. The neurological symptoms vary from confusion, coma, delirium, cognitive impairment including memory loss and attention defects; hypersomnia, abnormal movements (myoclonus, choreiform movements, oculomasticatory myorhythmia) or cerebellar ataxia. Brain magnetic resonance imaging (MRI) and T. whipplei PCR on the CSF are required. (1, 2, 3)
Antibiotic Treatment for WD
Antibiotic treatment is essential for treatment. However, the optimal regimen is uncertain and neurological involvement continues to be very difficult to manage. For such patients, an initial phase of an intravenous antibiotic that is active against T. whipplei and is known to penetrate the blood-brain barrier is required, followed by 12 months of oral maintenance therapy. Initial antibiotics include either ceftriaxone (2 g IV once daily), meropenem (1g three times daily) or penicillin G (4 MU IV every 4 hours) for two weeks, followed by with trimethorpim- sulfamethoxazole (TMP-SMX) [160 mg- 800 mg] twice a day) for one year. For those who have severe CNS symptoms or brain lesions, adjunctive corticosteroids may be beneficial, as is given for tuberculous meningitis. (4, 5)
Immune Reconstitution Inflammatory Syndrome (IRIS)
In the first few weeks following initiation of antibiotic treatment, some patients may develop an immune reconstitution inflammatory syndrome (IRIS) with high fever or other symptoms that mimic relapse or disease progression. PCR testing is often negative. IRIS reflects an inflammatory process that occurs despite successful therapy of the organism. (6)
Relapse in WD
Clinical relapses have been reported in about 25% of patients who remained PCR-positive. For patients who fail to respond to initial therapy or relapse, penicillin G (4 MU IV every 4 hours) or ceftiaxone (2 g IV twice daily) for four weeks followed TMP-SMX [160 mg- 800 mg SMX] twice a day) for one year. (7)
References
1-Agard C, Brisseau JM, Grossi O, Pattier S, Espitia-Thibault A, Le Goff B, Audrain M, Ponge T, Hamidou M. Two cases of atypical Whipple’s disease associated with cytoplasmic ANCA of undefined specificity. Scand J Rheumatol. 2012; 41: 246– 248. 2- Black DF, Aksamit AJ, Morris JM. MR imaging of central nervous system Whipple disease: a 15-year review. AJNR Am J Neuroradiol. 2010; 31: 1493– 1497. 3- Durand DV, Lecomte C, Cathebras P, Rousset H, Godeau P. Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple Disease. Societe Nationale Francaise de Medecine Interne. Medicine (Baltimore). 1997; 76: 170– 184. 4-Schnider PJ, Reisinger EC, Berger T, et al. Treatment guidelines in central nervous system Whipple's disease. Ann Neurol 1997; 41:561. 5- Feurle GE, Junga NS, Marth T. Efficacy of ceftriaxone or meropenem as initial therapies in Whipple’s disease. Gastroenterology. 2010; 138: 478– 486. 6- Lagier JC, Fenollar F, Lepidi H, Liozon E, Raoult D. Successful treatment of immune reconstitution inflammatory syndrome in Whipple’s disease using thalidomide. J Infect. 2010; 60: 79– 82. 7-Cooper GS, Blades EW, Remler BF, et al. Central nervous system Whipple's disease: relapse during therapy with trimethoprim-sulfamethoxazole and remission with cefixime. Gastroenterology 1994; 106:782.