Whipple's Disease Flashcards
Whipple’s Disease
Whipple’s disease is a rare multi-system disorder caused by Tropheryma whippelii infection. It is more common in those who are HLA-B27 positive and in middle-aged men
Features
malabsorption: diarrhoea, weight loss
large-joint arthralgia
lymphadenopathy
skin: hyperpigmentation and photosensitivity
pleurisy, pericarditis
neurological symptoms (rare): ophthalmoplegia, dementia, seizures, ataxia, myoclonus
Investigation
jejunal biopsy shows deposition of macrophages containing Periodic acid-Schiff (PAS) granules
Management
guidelines vary: oral co-trimoxazole for a year is thought to have the lowest relapse rate, sometimes preceded by a course of IV penicillin
Whipple’s Disease - Example Question
A 32-year-old man presents with loose stools or diarrhoea on all occasions for almost a year now, associated with intermittent, mild, generalised, crampy abdominal pain that has no obvious triggers. He has lost three stone (19 kilogrammes) in weight over the year despite not trying to. For nearly 10 years he has had episodes of arthralgia and fever which he has never thought to consult about. He once travelled to Gambia on his gap-year aged 18 and recalls several mosquito bites. He took full malaria prophylaxis as directed for the trip. His partner notices that as of the last 2-3 years he has had lapses in memory and is performing badly in his day-to-day tasks at work as a stoke broker such that he has now been made redundant. This has encouraged him to consult. On clinical examination, you find an emaciated gentleman with mild polyarthralgia and an ataxic gait. His Mini-Mental State Examination (MMSE) score is 22/30. Below are some of his blood test results:
Hb 90 g/l Platelets 300 * 109/l WBC 10 * 109/l MCV 70 fL Ferritin 8 micrograms/l
Na+ 140 mmol/l
K+ 2.9 mmol/l
Urea 11 mmol/l
Creatinine 110 µmol/l
Calcium 1.9 mmol/l
Magnesium 0.5 mmol/l
Rheumatoid factor negative
You organise a small bowel biopsy. What abnormality is the histology likely to show?
Increased increased intraepithelial lymphocytes with villous atrophy and crypt Hyperplasia > Deposition of macrophages containing PAS-positive granules within villi Transmural inflammation with multiple lymphoid aggregates Adenocarcinoma Carcinoid tumour cells with trabecular cell arrangements
The onset of Whipple’s disease features is insidious. Suspect it in persons with abdominal complaints, particularly malabsorption, plus neurological features. Incidentally, your differential for abdominal complaints and neurological features should include acute intermittent porphyria (AIP, which you can read about elsewhere on the site); but specifically, in this history, you would have expected a history of abdominal pain rather than malabsorption in AIP. The main point of the question is for you to recognise three key histological features they will commonly bring up in the exam in association with certain conditions, as below:
Increased intraepithelial lymphocytes with villous atrophy and crypt hyperplasia = coeliac disease
Deposition of macrophages containing PAS-positive granules within villi = Whipple’s disease
Transmural inflammation with multiple lymphoid aggregates = Crohn’s disease
Whipple’s Disease - Diagnosis: Example Question
A 55 year old man presents with chronic diarrhoea. He describes a 10 month history of poorly formed stools, occurring 2-3 times a day which are difficult to flush. This is intermittently associated with generalised abdominal discomfort. He has not noticed any blood in his stools.
He also describes a 9kg unintentional weight loss within this 10 month period. He cannot understand this, as he still has a good appetite and he has not changed his diet.
He is still working full time as a joiner, but has struggled on occasion when kneeling due to pains in his hips and knees and lethargy.
He has previously been fit and well, with a past medical history of childhood asthma. His two children are healthy. He has a family history ankylosing spondylitis, with his younger brother and dad suffering from the condition. He is not taking any regular medication.
On examination he is pale and thin. Cardiopulmonary examination was unremarkable. He has generalised lymphadenopathy with small palpable lymph nodes in his cervical, axillary and inguinal region. There is no organomegaly on abdominal palpation but there is generalised tenderness. His observations are within normal limits, apart from his temperature which has been consistently between 37.6ºC and 37.8ºC.
Which investigation would most likely give the diagnosis?
Blood tests > Gastroscopy with biopsies Colonoscopy Stool culture Joint xrays
The likely diagnosis here is Whipple’s disease. This is a notoriosuly difficult diagnosis in the clinical setting.
Whipple’s disease is a rare multisystem disorder caused by the actinobacteria Tropheryma whipplei. It is more common in middle aged, caucasian men and in those with HLA-B27.
Common symptoms include diarrhoea, abdominal pain, arthralgia and weight loss.
Other symptoms can be divided by system:
Cardiac: pericarditis, endocarditis, conduction defects
Respiratory: pleurisy
Neurological: seizures, myoclonus, cranial nerve lesions, dementia, confusion, insomnia and cerebellar signs.
Other: lymphadenopathy, fever, skin hyperpigmentation
The diagnosis relies on biopsy of affected tissue, usually in the duodenum. This shows infiltration of the lamina propria with periodic acid-Schiff stain (PAS)-positive macrophages. This is achieved by biopsies taken during a gastroscopy.
Whilst blood tests may indicate malabsorption, this is not specific. Stool cultures would rule out infective causes of the diarrhoea and weight loss, but again would not give a definitive diagnosis.
Whilst there are other important differentials to consider, including inflammatory bowel and coeliac disease, they cannot explain the diversity of symptoms.
Whipple’s Disease - Example Question
A 49-year-old man is referred to the gastroenterology outpatient clinic with a 6 month history of abdominal pain, diarrhoea and weight loss. These symptoms have been getting progressively worse over the past few weeks and are now associated with some arthrlagia affecting his hands and feet. The abdominal pain does not follow a particular pattern. It is associated with bloating and not relieved by defecation. He thinks in total he has lost around 10kg in the past 6 months.
The patient works in the IT industry and regularly travels to South East Asia. He is married and does not smoke.
On examination his pulse, blood pressure and temperature are normal. Generalised lymphadenopathy is noted in the cervical and inguinal regions. All the nodes felt were soft and non-tender. His wedding ring is loose and loss of the nail angle is noted. Examination of the abdomen is unremarkable other than some mild tenderness around the epigastric region. No organomegaly is detected. There was no evidence of swelling, erythema or synovitis in the hands or feet.
Bloods show the following:
Hb 10.4 g/dl Platelets 222 * 109/l WBC 6.96 * 109/l Na+ 139 mmol/l K+ 3.6 mmol/l Urea 5.1 mmol/l Creatinine 78 µmol/l Bilirubin 14 µmol/l ALP 120 u/l ALT 34 u/l γGT 55 u/l Albumin 26 g/l
What is the most appropriate treatment?
> IV penicillin then co-trimoxazole Prednisolone Rifampicin, isoniazid, pyrazinamide and ethambutol Gluten-free diet Highly active antiretroviral therapy
This patient has a number of typical features suggestive of the rare condition Whipple's disease: middle-aged male abdominal pain weight loss diarrhoea arthralgia lymphadenopathy clubbing (loss of the nail angle)
AIP vs Whipples
The onset of Whipple’s disease features is insidious. Suspect it in persons with abdominal complaints, particularly malabsorption, plus neurological features. Incidentally, your differential for abdominal complaints and neurological features should include acute intermittent porphyria but specifically you would expected a history of abdominal pain rather than malabsorption in AIP.
