Maciorkowska M.1B-D, Ustymowicz W.1B-D, Zakrzewski M.1B,C, Pryczynicz A.1B,C,E,F, Markowski A.2B,C,E, Romatowski J.3B,C,E, Guzińska-Ustymowicz K.*1A-F
A- Conception and study design; B - Collection of data; C - Data analysis; D - Writing the paper;
E- Review article; F - Approval of the final version of the article; G - Other (please specify)
Introduction:Whipple’s disease is a chronic systemic infectious disorder with Tropheryma whipplei as an etiologic agent, occurring rarely and affecting numerous organs and systems. The variety of symptoms and a non-typical course make it difficult to establish a proper diagnosis.
Purpose:In this study, etiopathogenesis, diagnostics and treatment of Whipple’s disease were presented based on the case report of 60-year-old man diagnosed with Whipple’s disease.
Case presentation:Persistent diarrhoea with weight loss, lymphadenopathy in the abdominal cavity and moderate microcytic anemia predominated in the clinical picture. Diagnosis was put based on the clinical picture and macroscopic assessment of the small intestine and the presence of macrophages filled with a PAS-positive substance in the lamina propria. To deepen diagnostics, samples collected were assessed showing macrophages with the damaged mucosa, containing numerous elongated micro-organisms whose ultrastructure corresponded to Tropheryma whipplei. The patient’s clinical conditions improved after antibiotic therapy.
Conclusions:It is vital to remember about Whipple’s disease in patients with chronic diseases due to a non-specific clinical picture and difficulties in establishing a proper diagnosis. When the disease is diagnosed unequivocally, proper and effective antibiotic therapy should be instituted immediately.
Keywords:infectious disease, systemic disease, Tropheryma whipplei,Whipple’s disease
Katarzyna Guzińska-Ustymowicz MD, PhD
Department of General Pathomorphology, Medical University of Bialystok, Poland
Tel: + 48 85 748 55 28
Progress in Health Sciences
Vol. 8(1) 2018 pp 213-219
© Medical University of Białystok, Poland
Whipple’s disease is a systemic, infectious disease affecting numerous organs. It most frequently affects the digestive, cardiovascular, nervous, respiratory and osteoarticular system. Tropheryma whipplei is its aetiological agent. Whipple’s disease is a rare disorder occurring in about 0.01% of the population, mainly Caucasians, males from 40 to 50 years old.
In 1907 year, George Hoyta Whipple described the disease for the first time, enumerating irregular bowel movements with steatorrhea, a significant body massloss, polyarthritis and abdominal pains with characteristic histopathological lesions . The syndrome with symptoms listed above was described as intestinal lipodystrophy. After 42 years, the present name - Whipple’s disease was introduced, when macrophages containing PAS – positive intracellular material were detected in autopsy or laparotomy (Periodic Acid Schiff staining). In this period, no data on effective treatment of this disease with antibiotics were available .
In the 1960’s, the bacterium believed to be similar to microorganisms causing tuberculosis was discovered and found responsible for Whipple’s disease.
The basis of diagnosis was detection of PAS-positive macrophages and identification of Tropheryma whipplei in electron microscopy . A pathogenic microorganism Tropheryma whipplei belongs to Gram-positive rods included in the family of Cellulomonadaceaea . In 2000 year, after collecting the samples from the material found in the patient’s cardiac valves, a pathogen was successfully cultured, using human fibroblasts. Further studies carried out in 2003 year resulted in the discovery of a complete genome of the bacterium, facilitating its detection by means if a specific polymerase chain reaction - PCR [5,6].
Whipple’s disease is a very rare disorder accounting for 30 cases a year in the world. It more frequently occurs in Caucasian males, from 50 to 60 years old than in women, mainly after the age of 70. The aetiological route has not been explained. The more frequent incidence of Whipple’s disease in farmers may suggest that bacteria are transmitted via water. Additionally, there are data indicating hereditary predispositions to this disorder. In Dobbins’s study , 25% of patients had HLA B27antigen probably increasing a risk of developing this disease. Furthermore, it has been speculated that people with Tropheryma whipplei infection have the impaired immune system characterised by a low cofactor of CD4/CD8 T cells, enhanced activity of Th2 and decreased activity of Th1, which is associated with overproduction of interleukin 4 (IL-4) and lower production of IL-12 and interferon-gamma, contributing to the development of this disease [8-11].
Clinical symptoms of the disease are non-specific and no characteristic pathognomonic symptoms can be observed, either. Its clinical course frequently suggests disorders of the digestive system with primary general symptoms like: diarrhoea, chills, fever, enlarged lymph nodes, abdominal pains and weight loss. Additionally, symptoms of the circulatory system, nervous system and osteoarticular system can be observed in patients [12-15].
In Whipple’ disease diagnostics, a great diagnostic value is attributed to the atrophy of intestinal villi in a bioptate of the small intestine mucosa, and the basic diagnosis is made on the presence of PAS-positive macrophages . Whipple’s disease is confirmed based on the bacterial RNA identification with PCR technique as well as the presence of this microorganism in electron microscopy . In the laboratory tests, an increase in inflammatory parameters, hypalbu-minaemia, hypokalaemia, hypocalcaemia, and microcytic anaemia associated with iron deficiency are determined. In this study, a clinical picture, diagnostics and treatment of a patient with Whipple’s disease were presented. It should be emphasised that a course of disorder is long-lasting, without significant symptoms, a lot of test results are non-specific and treatment is not effective enough to be considered satisfying.
A 60-year-old man was admitted to the Department of Internal Medicine and Gastroenterology of Jędrzej Śniadecki Provincial Polyclinical Hospital of Białystok due to pain in the middle epigastrium, chronic diarrhoea with loose bowels up to 8 in 24 hours, occasionally containing blood, a subfebrile state up to 37.4°C and significant weight loss (about 20 kg during last 4 months).
The patient reported malaise and pains in the lumbar region, the knee and hip joints. The patient’s history revealed 13-year seronegative arthritis, microcytic anaemia diagnosed 10 years ago and general lymphadenopathy. The man had pulmonary embolism in the past. No atherosclerotic lesions (in the coronary vessels) were found in the coronary angiography. The available medical documents didn’t contain any information about the length of lymphadenopathy, lymphnodes biopsy, synovial fluid analysis during 13-years of arthritis, cause of pulmonary embolism and information about the reason for coronary angiography.
Subjective examination revealed the features of malnutrition, pale skin and mucosal membranes, hemorrhagic rash on the skin in the sacral vertebrae region and lower extremities, enlarged painless cervical supraclavicular, axillar and inguinal lymph nodes, systolic murmur and pain in the middle epigastrium at palpation.
Patient in connection with symptoms such as chronic diarrhoea, fever and weight loss had diagnosed on the Department on Gastroenterology. The laboratory tests performed at admission showed severe macrocytic anaemia (HGB 6.9 g/dl), increased level of D-dimers (597) and INR – 9.27 and prolonged time of PT up to 81.2 sec and slightly enhanced inflammatory parameters (CRP- 17.1mg/l; OB- 21mm/h). Cancer markers (CEA and AFP) were within the norm. No pathogens were cultured in the stool.
Available ultrasonography of the abdominal cavity was normal without limphodenopathy. During the treatment the CT scan was perform and showed lymphadenopathy around the mesentery of the small intestine. Gastroscopy demonstrated mosaic gastric mucosa, non-uniform hyperaemic mucosa in the duodenal bulb and some blenching with hypertrophic folds and thickened villi in the outside bulbar region (Figure 1).