Non-convulsive status epilepticus associated with Whipple's disease.

A 69-year-old woman developed non-convulsive status epilepticus during inpatient investigation for abdominal pain. Initial detailed investigations did not identify the cause of seizures, but a jejunal biopsy and PCR testing in various fluids led to the diagnosis of Whipple's disease with neurological involvement. The seizures were controlled but she subsequently had moderate cognitive impairment. Whipple's disease is an important diagnosis, being treatable with antibiotics. Testing for Whipple's disease is not part of the recommended workup in for status epilepticus, but this case highlights the importance of considering this condition.

Whipple's disease: A rare disease that can be spotted by many doctors.

Whipple's disease, an extremely rare, chronic infection caused by Tropheryma whipplei, an actinobacterium ubiquitously present in the environment, is a multisystemic condition that can affect several organs. Therefore, Whipple's disease should always be considered by physicians working across various branches of medicine, including internal medicine, rheumatology, infectious diseases, gastroenterology, haematology, and neurology. Initially, Whipple's disease is challenging to diagnose due to both its rarity and non-specific clinical features, almost indistinguishable from rheumatological conditions. A few years later, the onset of gastrointestinal symptoms increases the specificity of its clinical picture and helps in reaching the correct diagnosis. Diagnosis is typically made by finding PAS-positive macrophages in the lamina propria at duodenal biopsy. PCR for Tropheryma whipplei is nowadays also increasingly available, and represents an undeniable help in diagnosing this condition. However, it may also be misleading as false positives can occur. If not promptly recognized and treated, central nervous system involvement may develop, which can be fatal. The therapeutic gold standard has not yet been fully established, particularly in cases of recurrent disease, neurological involvement, and an immune reconstitution inflammatory syndrome that may arise following the initiation of antibiotic therapy.

Use of bevacizumab in a patient with Whipple's disease: managing diagnostic uncertainty.

A man in his 30s with intellectual disability presented with 1 month of diarrhoea, weight loss and dyspnoea. Investigations were hampered due to significant anxiety. Laboratory tests detected microcytic anaemia and hypoalbuminaemia. CT demonstrated a fat-containing infiltrate in the mediastinum, mesentery and axillae, and pulmonary ground-glass infiltrates. Biopsy of the axilla showed cystic lymphatic malformations involving adipose tissue and lymph nodes, leading to a provisional diagnosis of generalised lymphatic anomaly. Over the subsequent 4 months, the patient's respiratory status deteriorated, leading to type 1 respiratory failure necessitating intubation. After multidisciplinary discussion, a decision was made to trial bevacizumab, an anti-VEGF agent, with subsequent improvement in respiratory status. While intubated, gastroscopy was performed; duodenal biopsies revealed pathognomonic changes of Whipple's disease, confirmed on PCR of duodenal and axillae biopsies. This was deemed the most likely unifying diagnosis; antibiotic treatment was commenced, bevacizumab was ceased, and the patient has remained well after 18 months.

Prosthetic valve endocarditis secondary to Tropheryma whipplei in a patient with chronic polyarthritis.

BACKGROUND: Whipple's disease is a chronic multisystemic infectious disease that rarely presents as culture-negative endocarditis. Most patients reported with Tropheryma whipplei endocarditis involve a native valve and few describe prosthetic valve disease. CASE PRESENTATION: A patient with chronic polyarthritis and previous mitral valve replacement developed decompensated heart failure without fever. Transesophageal echocardiography revealed a prosthetic mitral valve vegetation and he underwent prosthetic mitral valve replacement. Blood and prosthetic mitral valve cultures were unrevealing. Broad-range polymerase chain reaction (PCR) of the extracted valve and subsequent Periodic-acid-Schiff (PAS) staining established the diagnosis of T. whipplei prosthetic valve endocarditis. CONCLUSION: Whipple's disease may present as culture-negative infective endocarditis and affect prosthetic valves. Histopathology with PAS staining and broad-range PCR of excised valves are essential for the diagnosis. Greater clinical awareness and implementation of these diagnostic procedures should result in an increased reported incidence of this rare disease.

Contribution of PCR to Differential Diagnosis between Patients with Whipple Disease and Tropheryma whipplei Carriers.

Differentiation between Whipple disease (WD) patients and patients carrying Tropheryma whipplei but suffering from disease other than WD ("carriers") remains complex. We aimed to evaluate T. whipplei PCR among patients with WD and carriers in a large cohort at our referral clinical microbiology laboratory. This is an observational retrospective cohort study, including all patients between 2008 and 2020 with at least one positive result for T. whipplei using the real-time PCR RealCycler TRWH-UX kit. A total of 233 patients were included: 197 were considered carriers, and 36 had WD. Among the WD patients, 32 underwent biopsies, of which 18 (56%) had a positive periodic acid-Schiff (PAS) staining. Among the 27 duodenal biopsy specimens, 13 (48%) were PAS positive. PCR results before antibiotic treatment were positive in both feces and saliva in 16/21 WD (76%) patients and 68/197 (35%) carriers (P < 0.001). Duodenal biopsy specimens yielded positive PCR in 20/22 (91%) WD patients and 27/72 (38%) carriers (P < 0.001). The cycle threshold (CT) value detected in duodenal biopsy specimens from WD patients was significantly lower than that of carriers (P < 0.001), regardless of the PAS staining results. For a diagnosis of WD, duodenal PCR sensitivity and specificity at a CT value below 30 were 52.4% and >99.9%, respectively. The high specificity of duodenal PCR with low CT values may help confirming the diagnosis of WD, especially in patients with negative PAS results in digestive biopsy specimens, who represent half of all patients. A low PCR CT value from a duodenal biopsy specimen provides valuable guidance, especially in patients with PAS-negative results.

Whipple's disease with normal duodenal histology diagnosed by ileal biopsy using balloon endoscopy.

A 34 year-old previously healthy Japanese woman presented with a 4 year history of migratory arthralgia, chronic diarrhea, mild fever, and 10 kg weight loss. She was initially misdiagnosed with seronegative arthritis, followed by eosinophilic gastroenteritis. Oral prednisolone was found to be ineffective. Upper endoscopy revealed normal duodenal mucosa. Duodenal biopsy specimen indicated no abnormalities. However, balloon endoscopy revealed white shaggy villi in the ileum, and a biopsy specimen from which revealed diffuse infiltration of foamy macrophages in the lamina propria. These macrophages contained diastase-periodic acid-Schiff positive granules, consistent with Whipple's disease. Polymerase chain reaction analysis of DNA extracted from the ileum was compatible with Whipple's disease. In most previously reported cases of Whipple's disease, the duodenum was affected and duodenal biopsy specimens led to a diagnosis of Whipple's disease. Whipple's disease with normal duodenal histology is extremely rare and balloon endoscopy might be a useful diagnostic tool in such a case. The patient was treated with intravenous ceftriaxone and oral trimethoprim-sulfamethoxazole, and her symptoms improved one month after treatment. Balloon endoscopy performed 32 months later revealed complete improvement in lesions of the ileum.

Whipple's disease: Rare case of malabsorption with hyperpigmentation in a female.

Whipple's disease is a multisystem disorder and responds well to antibiotic therapy if treated timely. It is seen in the fourth to fifth decades of life with a male to female ratio of 10:1. It mainly affects the intestine, the central nervous system, and joints. To the best of our knowledge, we present the first case of duodenal Whipple's disease in an Indian female, who presented with hyperpigmentation and chronic diarrhea with malabsorption. Whipple's disease was diagnosed based on specific upper GI endoscopic and histopathology findings.

Whipple's disease diagnosed in a patient with suspected sarcoidosis.

This paper presents a case of a 51-year-old patient with chronic diarrhea, weight loss, polyarthralgia, and diffuse lymphadenopathy. Laboratory work-up showed anemia, leukocytosis and thrombocytosis, and increased C-reactive protein (CRP). Due to an inconspicuous differential leukocyte count and lymph node biopsy findings showing granulomatous lymphadenopathy, sarcoidosis was initially suspected. Colonoscopy found no abnormalities and duodenal biopsies showed negative Periodic acid-Schiff stains. However, PCR testing on these biopsies revealed Tropheryma whipplei DNA. Further PCR testing of urine and cerebrospinal fluid also revealed T. whipplei DNA. The patient was treated with ceftriaxone for 2 weeks followed by trimethoprim for a year. A rapid improvement of his symptoms was seen.

A Case of Whipple Disease With Cutaneous Manifestations.

ABSTRACT: Whipple disease (WD) is a rare bacterial infectious disease that is classically characterized by years of arthralgia, followed by malabsorption, diarrhea, and weight loss. However, WD may manifest in virtually any organ system, and patients with WD rarely develop subcutaneous erythema nodosum-like lesions. We report a case of a 51-year-old man diagnosed with WD who subsequently developed widely distributed erythematous subcutaneous nodules after 5 months of antibiotic therapy.

Whipple's disease: a fatal mimic

Whipple's Disease, a rare diagnosis caused by the slow-growing bacterium Tropheryma whipplei, most often presents with the classically described signs of malabsorption due to gastrointestinal colonization. However, it can also have signs and symptoms that clinically overlap with rheumatic diseases, potentially resulting in misdiagnosis. Furthermore, treatment with modern potent biologic immunosuppressive agents and classic disease modifying anti-rheumatic drugs (DMARDs) can lead to serious exacerbation of undiagnosed infections. We present the case of a middle-aged woman with long term complaints of arthalgias, who was diagnosed with seronegative rheumatoid arthritis and subsequently treated for almost 7 years with such immunosuppressive therapies. The patient's disease course included chronic diarrhea that abruptly intensified and culminated in fatal hypovolemic shock/sepsis. A diagnosis of WD was made by autopsy examination, wherein several organ systems were found to be heavily involved by Tropheryma whipplei organisms, and their identification was confirmed with histochemical and molecular evaluation. Notably, most bacterial organisms were located deeply in the submucosa/muscularis of affected organs, a practical reminder to practicing pathologists that challenges the classic histopathologic description of Whipple disease as an infiltration of predominantly lamina propria, and the potential for sampling bias in typically superficial endoscopic biopsies during routine procedures.

Fatal Whipple's disease with severe mental manifestations on relapse - case report and brief advances update.

We present the case of a 51-year-old male admitted for asthenia, fatigability, nausea, inappetence, weight loss, watery diarrhea, lower limb paresthesia and diagnosed after further investigations with Whipple's disease (WD). The evolution was favorable under antibiotic therapy but after a period of time the patient was no longer compliant to the treatment and psychotic manifestations, general status alteration and finally the decease occurred. WD is a condition caused by Tropheryma whipplei (TW) bacterium in people with altered macrophage degrading capacity and it is lethal without early treatment.

[Whipple's disease: very rare, fatal without treatment but easily cured]. / Whipples sjukdom: sällsynt, dödlig utan behandling, men lätt botad.

Whipple's disease is a chronic infectious disease that primarily affects the small intestine, but several organs can be involved simultaneously. The disease is caused by a gram-positive bacterium called Tropheryma whipplei. The disease is difficult to suspect because it is rare, and produces unspecific and long-term symptoms. Whipple's disease can lead to death if not treated. We here present a case of a man who presented with gastrointestinal symptoms in the form of diarrhea with blood, weight loss, fever, and lymphadenopathy and who was finally diagnosed with Whipple's disease 4 years after the occurrence of manifestations from the joints. The diagnosis was made both with 16S rRNA against Tropheryma whipplei and histopathologically from biopsy taken from the duodenum and distal ileum. The purpose of this case report is to raise awareness of a very rare disease that presented with a combination of symptoms similar to other and significantly more common diseases.

Clinical pitfalls of leishmaniasis and Whipple's disease hidden behind systemic lupus erythematosus: A case series.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that can affect major organs possibly leading to life-threatening complications and appears with heterogeneous clinical picture. SLE could present with broad spectrum of clinical and laboratory features that can resemble those of other diseases, such as hemopoietic malignancies, infections, or immune-mediated disorders. Its complexity and protean features overlap with many other diseases, hindering the differential diagnosis. Rarely, true overlap with other diseases may occur. Herein, we report a case series of two patients affected by infectious diseases, namely visceral leishmaniasis and Whipple's disease (WD), intertwined with clinical or serological features of SLE. In both cases, several confounding factors have led to a delay in the diagnosis. Moreover, we first describe the persistent elevation of autoantibodies and a monoclonal gammopathy in a patient with WD. Awareness of unusual presentations of infections or other rare disorders, which may be encountered in clinical practice when taking care of SLE patients, is essential for timely diagnosis and treatment of potentially lethal diseases.

Limbic encephalitis as a relapse of Whipple's disease with digestive involvement and spondylodiscitis.

INTRODUCTION: Many clinical manifestations can be related to Tropheryma whipplei infection. CASE REPORT: We report a Tropheryma whipplei limbic encephalitis developed as a relapse of classical Whipple's disease. DISCUSSION: This case is to the best of our knowledge the first proof of the effective brain-blood barrier crossing of both doxycycline and hydroxychloroquine as demonstrated by direct concentration monitoring on brain biopsy.

Whipple's disease and Tropheryma whipplei infections: when to suspect them and how to diagnose and treat them.

PURPOSE OF REVIEW: The delay between first clinical signs and diagnosis of Whipple's disease and Tropheryma whipplei infections is more than 6 years, and relapses are frequently observed, resulting in a need for clinicians to be aware of this infection. RECENT FINDINGS: 18 FDG-PET is useful in the diagnosis and the follow-up of patients (particularly in case of neurological involvement). Histological involvement remains the goldstandard for classic Whipple's disease diagnosis. PCR performed on biopsies of fluid is the main tool for the diagnosis of localized chronic infections. PCR performed on urine samples should become an important role of noninvasive diagnostic strategies, while T. whipplei PCR performed on saliva and stool lack specificity. Because of lifetime susceptibility to T. whipplei and in-vitro susceptibility data, a 1-year course of doxycycline and hydroxychloroquine followed by a lifelong treatment by doxycycline is recommended for Whipple's disease, localized endocarditis and encephalitis. SUMMARY: Clinical involvement of the different T. whipplei infections is well described, as well as the treatment of Whipple's disease, endocarditis and encephalitis. The place of PCR performed on urine remains to be clarified for diagnosis of localized T. whipplei infections and acute infections as well as the optimal treatment for arthritis and acute infections.

IRF4 haploinsufficiency in a family with Whipple's disease.

Most humans are exposed to Tropheryma whipplei (Tw). Whipple's disease (WD) strikes only a small minority of individuals infected with Tw (<0.01%), whereas asymptomatic chronic carriage is more common (<25%). We studied a multiplex kindred, containing four WD patients and five healthy Tw chronic carriers. We hypothesized that WD displays autosomal dominant (AD) inheritance, with age-dependent incomplete penetrance. We identified a single very rare non-synonymous mutation in the four patients: the private R98W variant of IRF4, a transcription factor involved in immunity. The five Tw carriers were younger, and also heterozygous for R98W. We found that R98W was loss-of-function, modified the transcriptome of heterozygous leukocytes following Tw stimulation, and was not dominant-negative. We also found that only six of the other 153 known non-synonymous IRF4 variants were loss-of-function. Finally, we found that IRF4 had evolved under purifying selection. AD IRF4 deficiency can underlie WD by haploinsufficiency, with age-dependent incomplete penetrance.