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

Yogita Munjal; Sachin D Munjal; Richa Tiwari

doi:10.4103/IJPM.IJPM_887_20

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CASE REPORT

Year : 2021 | Volume : 64 | Issue : 4 | Page : 788-790

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

Yogita Munjal¹, Sachin D Munjal², Richa Tiwari³
¹ Department of Pathology, Gastro-Liver Care, Satyam Clinic, Prakashpuram, Saharanpur, Uttar Pradesh, India
² Department of Gastroenterology, Gastro-Liver Care, Satyam Clinic, Prakashpuram, Saharanpur, Uttar Pradesh, India
³ Department of Radio Diagnosis, SMMH Medical College, Saharanpur, Uttar Pradesh, India

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Date of Submission	30-Jul-2020
Date of Decision	18-Aug-2020
Date of Acceptance	25-Aug-2020
Date of Web Publication	20-Oct-2021

Abstract

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.

Keywords: Malabsorption, periodic acid-schiff (PAS), skin hyper pigmentation, upper GI endoscopy, Whipple's disease

How to cite this article:
Munjal Y, Munjal SD, Tiwari R. Whipple's disease: Rare case of malabsorption with hyperpigmentation in a female. Indian J Pathol Microbiol 2021;64:788-90

How to cite this URL:
Munjal Y, Munjal SD, Tiwari R. Whipple's disease: Rare case of malabsorption with hyperpigmentation in a female. Indian J Pathol Microbiol [serial online] 2021 [cited 2023 Mar 28];64:788-90. Available from: https://www.ijpmonline.org/text.asp?2021/64/4/788/328580

Introduction

Whipple's disease, a chronic systemic illness principally affecting gastrointestinal system and presenting with chronic diarrhea and malabsorption, is caused by Tropheryma whipplei, a rod-shaped microorganism.^[1] The characteristic histopathology of Whipple's disease is the infiltration of various organs with macrophages containing the T. whipplei bacillus. This infiltration has a predilection for the lamina propria of the small intestine, the mesenteric lymph nodes, the cardiac valves, and the central nervous system.^[2] Delay in the diagnosis and treatment can cause the disease to spread which can be fatal.

Third generation cephalosporins with sulfamethoxazole and trimethoprim for 1 year is the mainstay of treatment.^[3]

Case Report

We report a 55-year-old lady presented with chronic diarrhea of 7-month duration. She used to pass 4–6 excessive watery large volume, painless, nonbloody stools with nocturnal symptoms and incontinence. It was associated with features of malabsorption like pedal edema, extreme weakness, and body pain.

She had history of multiple admissions due to diarrhea and was treated symptomatically. In due course, she also complained of darkening of skin. There was no history of any neurological, ophthalmological, and cardiological involvement. On examination, she had hyperpigmented coarse skin [Figure 1]a and [Figure 1]b pallor, bald tongue, and pedal edema. Her biochemical investigation showed low albumin (2.8 gm/dL) and low hemoglobin (9 gm/dL). She had Low vitamin B12, vitamin D, and folate levels with normal serum total IgA and antitissue transglutaminase antibody (IgA tTG) levels. The stool examination for fat was positive while it was negative for ova, cyst, and opportunistic infections. Ultrasound abdomen showed hyperechoic intra-abdominal lymph nodes. Echocardiography was normal. Upper gastrointestinal endoscopy revealed normal esophagus with swollen duodenal folds showing numerous whitish to yellowish plaques over the mucosa [Figure 2]a and [Figure 2]b. Multiple (>5 in number) biopsy specimens were taken from the duodenum. Colonoscopy with terminal ileoscopy was unremarkable. Histopathological examination of duodenal biopsy revealed broadening of villi and diffuse infiltration of lamina propria with macrophages having a granular pinkish cytoplasm [Figure 3]a. Occasional fat vacuoles were seen in the lamina propria with mild chronic inflammatory cell infiltrate comprising lymphocytes, plasma cells, and eosinophils [Figure 3]b. The cytoplasm of the macrophages was periodic acid-schiff (PAS) positive, resistant to PAS-diastase and negative with Ziehl Neelsen (Z-N) stain, morphologically consistent with Whipple's disease [Figure 4]a, [Figure 4]b, [Figure 4]c. Patient was treated with ceftriaxone 2 gm daily for 10 days followed by trimethoprim sulfmethoxyzole (TMP/SFX) combination. During the course of treatment, she developed ataxia, nystagmus, and later altered sensorium. Her magnetic resonance imaging (MRI) brain and cerebrospinal fluid (CSF) examination were normal. She had aspiration pneumonia and was put on invasive ventilatory support but succumbed to her illness.

Figure 1: (a and b) Hyperpigmentation of skin

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Figure 2: (a and b) Upper GI endoscopy showing swollen duodenal folds with whitish plaques

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Figure 3: Whipple's disease, H and E (a) Broadening and flattening of intestinal villi with infiltration of lamina propria with macrophages. (× 100). (b) Lamina propria showing fat vacuoles and macrophages packed with intracytoplasmic granules (× 400)

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Figure 4: Whipple's disease (a) Per iodic acid-schiff, macrophages showing intense eosinophilic PAS-positive granular cytoplasm. (×400). (b) PAS with diastase, macrophages showing positivity for PAS with diastase (×400). (c) Ziehl-Neelsen stain, showing absence of acid-fast bacilli (×400)

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Discussion

Whipple's disease, also well known as intestinal lipodystrophy, was first recognized by Sir George Hoyt Whipple in 1907.^[4] Black-Schaffer in 1949 gave the histological features for Whipple's disease.^[5] Bacteria as the cause of Whipple's disease was proved by the first successful treatment of a patient with chloramphenicol in 1952.^[6] Whipple's can occur at any age with a mean age around 50 years.^[7] It is seen rarely in females. However, our case, to the best of our knowledge, is the first report of duodenal Whipple's disease in an Indian female.

The predominant complaint of patients in Whipple's disease is chronic diarrhea with malabsorption. It commonly involves the small intestine but rarely involves the esophagus and large intestine.^[8] It can also cause symmetrical polyarticular nonerosive arthritis mainly involving the knee joint and wrist joint. Neurological symptoms include triad of dementia, external ophthalmoplegia, and facial myoclonus. In few patients, it can cause lymphedenopathy, endocarditis, and ocular involvement (vitritis, uveitis, retinitis). Hyperpigmentation is a less common sign. It may be due to vitamin D malabsorption leading to increased levels of melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) through compensatory secondary hyperparathyroidism or may be due to vitamin B12 malabsorption or due to hypothalamic and adrenal insufficiency.^{[9],[10],[11]}

Upper gastrointestinal endoscopy with duodenal biopsy is the primary method of diagnosis. Endoscopy shows swollen duodenal folds with whitish plaques-like patches in majority of patients.

On routine evaluation, patient usually has anemia, low albumin, low vitamin B12, folate, and vitamin D level, and positive stool fat estimation. Ultrasound abdomen shows highly ecohogenic intra-abdominal lymph nodes due to high lipid contents. Routine CSF sampling is indicated even in the absence of neurological symptoms.

Diagnostic gastro-intestinal mucosal biopsy reveals macrophages infiltrating lamina propria and muscularis mucosa (and sometimes sub mucosa). Fat vacuoles can also be seen in the lamina propria although number of lymphocytes may not be increased. The cytoplasm of macrophage is coarsely granular and stains intensely positive with PAS.^[12]

The important histopathologic differential diagnosis of Whipple's disease includes mycobacterium avium intracellular complex (MAIC) and histoplasmosis.^[13] The macrophages in histoplasmosis show a clear halo peripherally surrounded by blue, dot-like inclusions. The budding yeast forms are demonstrated by PAS and silver stains. The common features of Whipple's disease and MAIC infection have been discussed in detail in the past. Distinction between them is proved by use of the Z-N stain that stains negative in Whipple's disease and positive in MAIC^[12]

Microscopically, xanthogranulomatous cholecystitis extending to the intestine may be a close differential of Whipple's disease.^[14]

The electron microscopic presence of bacilli has been considered to be specific for Whipple's disease. But advances in immunocytochemistry and molecular biology have overcome electron microscopic findings.^[15] For identification of the organism by PCR in clinical specimens, unique species-specific primers-16S ribosomal DNA (rDNA) sequence was selected.^[16] This test is now being used as gold standard method for diagnosing Whipple's disease.

There is no general consensus regarding treatment. Most commonly it is treated with intravenous ceftriaxone (2 gm iv once a day) for 2 weeks followed by oral TMP/SFX (960 mg twice daily) for 12 months. Other therapies include intravenous ceftriaxone (2 gm iv once a day) for 2 weeks followed by 3 months of oral TMP/SFX (960 mg twice daily) or doxycycline (100 mg twice daily) with hydroxychloroquine (200 mg thrice daily) for 1 year. Response to therapy is monitored clinically along with endoscopy followed by biopsy. Patient on continuous treatment improves dramatically with disappearance of extra intestinal symptoms within few days although gastrointestinal symptoms and malnutrition might take a few months.^[17]

Therefore, histological features compatible with the diagnosis of Whipple's disease along with PAS positivity with diastase resistant and a negative acid-fast stain is the diagnostic hallmark of Whipple's disease.

Declaration of patient consent

We certify that we have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her names and initials will not be published and due efforts will be made to conceal her identity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

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