A. Introduction

1. Also called intestinal lipodystrophy
2. Bacterial infectious disease
3. Organism
   1. Tropheryma whippelii
   2. Gram positive rod
   3. Member of actinomycete group of atypical bacteria
   4. Original identification by PCR detection of jejunal biopsy specimens
4. May be detected in red blood cells by PCR [2]
5. Recently cultured in human fibroblast line HEL [3]
6. Complete genome cloned [4]
   1. Lack of metabolic capabilities leads to host restriction
   2. Highly variable surface structures probably allow for evasion of host immunity

B. Symptoms and Signs

1. Prodromal followed by longer "steady-state" symptoms
2. Prodromal symptoms nonspecific, including arthralgias, arthritis
3. ~15% of Whipple's patients in steady state disease do not have classic signs and symptoms
4. Steady State Signs and Symptoms
   1. Systemic
   2. Gastrointestinal
   3. Musculoskeletal
   4. Central nervouse system (CNS)
   5. Cardiac
5. Systemic
   1. Fever
   2. Weight Loss
   3. Lymphadenopathy ~55%
6. Diarrhea ± malabsorption (usually with weight loss) ~50%
7. Polyarthritis
8. Abdominal pain
9. CNS <10%
   1. Focal and nonfocal deficits
   2. Headaches
   3. Vasculitis - headaches, seizures
   4. Psychosis
   5. Insomnia [5]
   6. Severe CNS infection associated with 25% mortality at 4 years
10. Cardiac Disease
    1. Pericarditis ± effusion
    2. Myocarditis
    3. Endocarditis - may be afebrile [6]

C. Laboratory Findings

1. Low Serum Carotene Level (malabsorption marker): 95%
2. Hypoalbuminemia: 93%
3. Fecal Fat >7gm/24 hr: 91%
4. Low Serum Iron: 86%
5. Anemia: 75%
6. Elevated ESR (mean 46mm/hr): 70%

D. Diagnosis

1. Histopathology
   1. Small Intestine (jejunal) biopsy specimen with foamy macrophages
   2. Organisms are PAS+ and resistant to diastase
   3. Histopathology was previously the gold standard
   4. Noncaseating epithelioid granulomas, often in lymph nodes, in ~10% of classic Whipples
2. Polymerase Chain Reaction (PCR)
   1. PCR based detection in either RBC or mononuclear cells is now the gold standard
   2. PCR based detection methods are >95% sensitive, 100% specific
   3. Can also be used fairly accurately to assess clinical efficacy of treatment
3. Culture and Immunologic Detection [7]
   1. Biopsy specimens from small intestine obtained and grown in culture
   2. Biopsies from gastrointestinal tract must be decontaminated with antibiotics first
   3. Mouse anti-T. whippelii polyclonal antibodies used to detect presence of organism

E. Treatment

1. Highly responsive to many antibiotics
   1. Sulfa agents (TMP/SMX) usually first line with very low relapse rate (<5%)
   2. Streptomycin with pencillin also has low relapse rate (~12%)
   3. Ceftriaxone and penicillins are also effective
   4. Doxycycline or tetracycline has higher relapse rates (up to 32%)
   5. Chloramphenicol also active
2. Recommended Treatment
   1. Non-CNS disease: doxycycline + hydroxychloroquine (Plaquinel®) 12-18 months [1]
   2. Alternatively, ceftriaxone OR penicillin + streptomycin for 2 weeks initially
   3. Followed by 12-18 months of TMP/SMX (Bactrim®, Septra®, others)
3. Refractory disease should be treated in experimental setting with other antibiotics
4. Glucocorticoids may provide some relief but should ALWAYS be combined with antibiotics
5. Prolonged course necessary to prevent relapses
6. Interferon gamma may be useful in antibiotic-refractory Whipple's Disease [8]
7. Carbamazepine may be effective for CNS symptoms including seizures, insomnia

References

1. Fenollar F, Puechal X, Raoult D. 2006. NEJM. 356(1):55
2. Misbah SA, Aslam A, Costello C. 2004. Lancet. 363(9409):654
3. Raoult D, Birg ML, La Scola B, et al. 2000. NEJM. 342(9):621
4. Bentley SD, Malwald M, Murphy LD, et al. 2003. Lancet. 361(9358):637
5. Lieb K, Maiwald M, Berger M, Voderholzer U. 1999. Lancet. 354(9194):1966
6. Gubler JGH, Kuster M, Dutly F, et al. 1999. Ann Intern Med. 131(2):112
7. Raoult D, La Scola B, Lecocq P, et al. 2001. JAMA. 285(8):1039
8. Schneider T, Stallmach A, von Herbay A, et al. 1998. Ann Intern Med. 129(11):875