Whipple's disease. Report of five cases with different clinical features

Whipple's disease (WD) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female) ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up.

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Tropheryma whipplei, Immunosuppression and Whipple's Disease: From a Low-Pathogenic, Environmental Infectious Organism to a Rare, Multifaceted Inflammatory Complex

Digestive Diseases ◽

10.1159/000369538 ◽

2015 ◽

Vol 33 (2) ◽

pp. 190-199 ◽

Cited By ~ 10

Author(s):

Thomas Marth

Keyword(s):

Heart Valves ◽

Clinical Manifestations ◽

Systemic Infection ◽

Tropheryma Whipplei ◽

Molecular Techniques ◽

Whipple’S Disease ◽

Whipple's Disease ◽

New Findings ◽

The Central Nervous System ◽

Body Compartments

Background: The actinobacterium Tropheryma whipplei was detected 20 years ago by molecular techniques, and following its culture has been characterized as the cause of a systemic infection known as Whipple's disease (WD). T. whipplei occurs in the environment, is prevalent only in humans, is believed to be transmitted via oral routes and to be host dependent. Key Messages: The classical form of T. whipplei infection, i.e. classical WD (CWD), is rare. It is well defined as slowly progressing chronic infection with arthralgia, diarrhea and weight loss, mostly in middle-aged men. However, current research revealed a much broader spectrum of clinical features associated with T. whipplei infection. Thus, T. whipplei may cause acute and transient infections (observed primarily in children) and the bacterium, which is found in soil and water, occurs in asymptomatic carriers as well as in CWD patients in clinical remission. In addition, T. whipplei affects isolated and localized body compartments such as heart valves or the central nervous system. Subtle immune defects and HLA associations have been described. New findings indicate that the progression of asymptomatic T. whipplei infection to clinical WD may be associated with medical immunosuppression and with immunomodulatory conditions. This explains that there is a discrepancy between the widespread occurrence of T. whipplei and the rareness of WD, and that T. whipplei infection triggered by immunosuppression presents with protean clinical manifestations. Conclusions: This review highlights recent findings and the clinical spectrum of infection with T. whipplei and WD, focusing specifically on the role of host immunity and immunosuppression. Current concepts of the pathogenesis, diagnosis and therapy are discussed.

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Ocular Whipple's Disease: Therapeutic Strategy and Long-Term Follow-Up

Ophthalmology ◽

10.1016/j.ophtha.2012.01.024 ◽

2012 ◽

Vol 119 (7) ◽

pp. 1465-1469 ◽

Cited By ~ 31

Author(s):

Valérie Touitou ◽

Florence Fenollar ◽

Nathalie Cassoux ◽

Helene Merle-Beral ◽

Phuc LeHoang ◽

...

Keyword(s):

Therapeutic Strategy ◽

Whipple’S Disease ◽

Whipple's Disease ◽

Long Term Follow Up

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Sight-threatening progressive corneo-scleral involvement in porphyria cutanea tarda

BMJ Case Reports ◽

10.1136/bcr-2021-245160 ◽

2021 ◽

Vol 14 (10) ◽

pp. e245160

Author(s):

Sonali Prasad ◽

Vidhata Vidhata ◽

Subhash Prasad

Keyword(s):

Porphyria Cutanea Tarda ◽

Clinical Manifestations ◽

Ocular Involvement ◽

Slit Lamp ◽

Uroporphyrinogen Decarboxylase ◽

Progressive Loss ◽

The Right ◽

Lost To Follow Up ◽

Test Serum

Porphyria cutanea tarda is the most common type of porphyria. It is associated with a deficiency of uroporphyrinogen decarboxylase enzyme responsible for heme synthesis. Clinical manifestations are predominantly dermatological and very rarely present with ocular involvement. Although scleral thinning in the interpalpebral area is a well-documented entity, sight-threatening corneal involvement is rarely described. We, herein report a case of a 58-year-old man who presented with ocular surface dryness, photophobia and mild redness. Slit-lamp biomicroscopy revealed corneo-scleral thinning in both eyes. The diagnosis was confirmed with a urine porphyrin test, serum iron and serum ferritin levels. We started him on conservative management after which he was lost to follow-up. He presented again after 6 years with total corneal opacification and progressive loss of vision in the right eye.

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Whipple's Disease and “Tropheryma whippelii”

Clinical Microbiology Reviews ◽

10.1128/cmr.14.3.561-583.2001 ◽

2001 ◽

Vol 14 (3) ◽

pp. 561-583 ◽

Cited By ~ 157

Author(s):

Fabrizio Dutly ◽

Martin Altwegg

Keyword(s):

Bacterial Species ◽

Periodic Acid ◽

Clinical Manifestations ◽

The Body ◽

Rrna Gene ◽

Low Grade ◽

Whipple’S Disease ◽

Major Step ◽

Whipple's Disease ◽

Initial Symptoms

SUMMARY Whipple's disease is a rare bacterial infection that may involve any organ system in the body. It occurs primarily in Caucasian males older than 40 years. The gastrointestinal tract is the most frequently involved organ, with manifestations such as abdominal pain, malabsorption syndrome with diarrhea, and weight loss. Other signs include low-grade fever, lymphadenopathy, skin hyperpigmentation, endocarditis, pleuritis, seronegative arthritis, uveitis, spondylodiscitis, and neurological manifestations, and these signs may occur in the absence of gastrointestinal manifestations. Due to the wide variability of manifestations, clinical diagnosis is very difficult and is often made only years or even decades after the initial symptoms have appeared. Trimethoprim-sulfamethoxazole for at least 1 year is usually considered adequate to eradicate the infection. The microbiological diagnosis of this insidious disease is rendered difficult by the virtual lack of culture and serodiagnostic methods. It is usually based on the demonstration of periodic acid-Schiff-positive particles in infected tissues and/or the presence of bacteria with an unusual trilaminar cell wall ultrastructure by electron microscopy. Recently, the Whipple bacteria have been characterized at the molecular level by amplification of their 16S rRNA gene(s). Phylogenetic analysis of these sequences revealed a new bacterial species related to the actinomycete branch which was named “Tropheryma whippelli.” Based on its unique 16S ribosomal DNA (rDNA) sequence, species-specific primers were selected for the detection of the organism in clinical specimens by PCR. This technique is currently used as one of the standard methods for establishing the diagnosis of Whipple's disease. Specific and broad-spectrum PCR amplifications mainly but not exclusively from extraintestinal specimens have significantly improved diagnosis, being more sensitive than histopathologic analysis. However, “T. whippelii” DNA has also been found in persons without clinical and histological evidence of Whipple's disease. It is unclear whether these patients are true asymptomatic carriers or whether differences in virulence exist among strains of “T. whippelii” that might account for the variable clinical manifestations. So far, six different “T. whippelii” subtypes have been found by analysis of their 16S-23S rDNA spacer region. Further studies of the pathogen “T. whippelii” as well as the host immune response are needed to fully understand this fascinating disease. The recent cultivation of the organisms is a promising major step in this direction.

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Clinical manifestations and diagnosis of Whipple's disease: case report

Revista Médica de Minas Gerais ◽

10.5935/2238-3182.20150051 ◽

2015 ◽

Vol 25 (2) ◽

Author(s):

Henrique Carvalho Rocha ◽

Wóquiton Rodrigues Marques Martins ◽

Marcos Roberto de Carvalho ◽

Lígia Menezes do Amaral

Keyword(s):

Case Report ◽

Clinical Manifestations ◽

Whipple’S Disease ◽

Whipple's Disease ◽

Disease Case

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Isolated Knee Arthritis as Early and Only Symptom of Whipple’s Disease

Case Reports in Medicine ◽

10.1155/2018/3417934 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Dario Giunchi ◽

Natalie Marcoli ◽

Luca Deabate ◽

Marco Delcogliano ◽

Enrique Testa ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Scientific Literature ◽

Systemic Disease ◽

Whipple’S Disease ◽

Whipple's Disease ◽

Knee Arthritis ◽

Specific Data ◽

Pas Staining ◽

Inflammatory Infiltrates ◽

Disease Specialist

We report a case of isolated Whipple’s disease involving the knee of a 64-year-old female patient who presented recurrent monoarthritis whose origin was not clear. Initially, the cause of the gradually invalidating symptoms was related to a meniscal lesion and a diffuse minor grade chondropathy, but pain and functional impairment suggested that more exams were needed. Biopsies were performed during arthroscopy. The histology showed highly inflammatory infiltrates with PAS staining negative for Tropheryma while PCR revealed the infection with Tropheryma whipplei. This, following the recommendation of a rheumatologist and infectious disease specialist, led to biopsies of the gastrointestinal tract and analysis of the cerebrospinal fluid that showed no other organ involvement. This confirms the scientific literature that an isolated monoarthritis without involvement of the gastrointestinal tract caused by this bacterium is rare but can occur as an early manifestation of potentially fatal systemic disease. Moreover, a review of the scientific literature showed the uncertainty about epidemiology of this rare disease, suggesting that more and specific data are required.

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Antibiotic Susceptibility of Tropheryma whipplei in MRC5 Cells

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.3.747-752.2004 ◽

2004 ◽

Vol 48 (3) ◽

pp. 747-752 ◽

Cited By ~ 87

Author(s):

Areen Boulos ◽

Jean-Marc Rolain ◽

Didier Raoult

Keyword(s):

Clinical Manifestations ◽

Extensive Study ◽

Tropheryma Whipplei ◽

Whipple’S Disease ◽

Chronic Infections ◽

Pcr Assay ◽

Whipple's Disease ◽

Reference Treatment ◽

Clinical Observations ◽

Reference Strains

ABSTRACT Whipple's disease is considered a rare chronic disease with a broad spectrum of clinical manifestations. Several antibiotics have been used for the treatment of this disease, and the current reference treatment was determined empirically on the basis of only a few clinical observations. Patients should be treated for months, and many relapse after antibiotic withdrawal. We report here the first extensive study on the susceptibilities of three reference strains of Tropheryma whipplei to antibiotic in cell culture by using a real-time PCR assay as previously described. We found that doxycycline, macrolides, ketolides, aminoglygosides, penicillin, rifampin, teicoplanin, chloramphenicol, and trimethoprim-sulfamethoxazole were active, with MICs ranging from 0.25 to 2 μg/ml. Vancomycin was somewhat active at an MIC of 10 μg/ml. We found heterogeneity in the susceptibility to imipenem, with one strain being susceptible and the two other strains being resistant. Cephalosporins, colimycine, aztreonam, and fluoroquinolones were not active. We also demonstrated that a combination of doxycycline and hydroxychloroquine was bactericidal. This combination has been shown to be active in the treatment of patients suffering from chronic infections with Coxiella burnetii, a bacterium that is also found intracellularly in acidic vacuoles. We believe, then, that this combination therapy should be further evaluated in clinical trials for the treatment of Whipple's disease.

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Constrictive pleuropericarditis: a dominant clinical manifestation in Whipple’s disease

BMC Infectious Diseases ◽

10.1186/1471-2334-13-579 ◽

2013 ◽

Vol 13 (1) ◽

Cited By ~ 6

Author(s):

George Stojan ◽

Michael T Melia ◽

Sandeep J Khandhar ◽

Peter Illei ◽

Alan N Baer

Keyword(s):

Clinical Manifestation ◽

Whipple’S Disease ◽

Whipple's Disease

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A long-term retrospective study of patients with biopsy-proven cryptogenic organizing pneumonia

Chronic Respiratory Disease ◽

10.1177/1479973119853829 ◽

2019 ◽

Vol 16 ◽

pp. 147997311985382 ◽

Cited By ~ 2

Author(s):

Ying Zhou ◽

Lei Wang ◽

Mei Huang ◽

Jingjing Ding ◽

Hanyi Jiang ◽

...

Keyword(s):

Systemic Disease ◽

Clinical Manifestations ◽

Clinical Information ◽

Organizing Pneumonia ◽

Cryptogenic Organizing Pneumonia ◽

Frequent Relapses ◽

Incidence Risk ◽

Relapse Group

Cryptogenic organizing pneumonia (COP) is characterized by good response to corticosteroids, but frequent relapses after reduction or cessation of treatment are noted. The incidence, risk factors of relapse, and long-term outcomes of patients with COP remain undetermined. Patients with COP from September 2010 to December 2017 were enrolled. Hospital and office records were used as data sources. Clinical information, lab examinations, chest radiographs, treatment courses, and follow-up data were collected. Relapse group was defined as worsening of clinical manifestations in combination with progression of radiographic abnormalities in the absence of identified causes. Eighty-seven patients with COP were enrolled. Of them, 73 patients were treated with corticosteroids with relapse rate yielding 31.5% (23 of 73). Eleven patients were treated with macrolides and none of them relapsed. Fever was more common (65.2% vs. 32.0%, p = 0.004), C-reactive protein (CRP) was higher (31.5 ± 39.4 mg/L vs. 17.5 ± 32.2 mg/L, p = 0.038), and diffusion capacity for carbon monoxide (DLCO) % predicted was lower (45.9 ± 14.2% vs. 57.6 ± 18.5%, p = 0.050) in relapse group compared to nonrelapse group. Four patients who presented with organizing pneumonia (OP) as the first manifestation were ultimately diagnosed with OP secondary to autoimmune disease in follow-up. We showed relapse was common in COP patients treated with corticosteroids, but the prognosis was favorable. Fever, elevated CRP, and a reduced DLCO were related to relapse. As OP may not always be cryptogenic, a careful follow-up should be programmed to diagnose the underlying systemic disease.

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Whipple’s disease

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0303 ◽

2020 ◽

pp. 2909-2911

Author(s):

Florence Fenollar ◽

Didier Raoult

Keyword(s):

Clinical Manifestations ◽

Central Nervous System Disease ◽

Prolonged Treatment ◽

Term Therapy ◽

Whipple’S Disease ◽

Whipple's Disease ◽

System Disease ◽

Systemic Manifestations ◽

Long Term Therapy

Whipple’s disease is an uncommon infection caused by the actinomycete Tropheryma whipplei, most commonly diagnosed when overt small intestinal disease leads to malabsorption, but with protean other clinical manifestations (e.g. systemic, neurological, or cardiological). Diagnosis usually depends upon demonstration of classical histological features in the small intestine, and positive identification of T. whipplei DNA by polymerase chain reaction. Treatment is with antibiotics, initially doxycycline and hydroxychloroquine followed by long-term therapy with doxycycline. Clinical improvement occurs within a few weeks, but prolonged treatment for at least a year is recommended. Relapse can occur, even after many years, especially when progressive central nervous system disease occurs in the absence of other systemic manifestations.

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