Eosinophilic vasculitis : A rare presentation of Whipple ’ s disease

1Department of Medicine, University of Western Ontario, London, Ontario; 2Department of Medicine; 3Department of Pathology, McGill University, Montreal, Quebec Correspondence: Dr Waleed Al-hamoudi, 339 Windermere Road, Room C4-216, University of Western Ontario, London, Ontario N6A 5A5. Telephone 519-697-4811, fax 519-663-2967, e-mail walhamoudi@gmail.com Received for publication June 21, 2006. Accepted June 22, 2006 W Al-hamoudi, F Habbab, C Nudo, A Nahal, K Flegel. Eosinophilic vasculitis: A rare presentation of Whipple’s disease. Can J Gastroenterol 2007;21(3):189-191.

Patients usually present with arthralgias, abdominal pain, fever or weight loss.Neurological and cardiovascular manifestations have also been described early on, making the diagnosis of this rare disease very challenging (3)(4)(5).Typically, digestive symptoms dominate the clinical picture as the disease progresses.
We report a case of Whipple's disease presenting a skin rash: an eosinophilic vasculitis with eosinophilia.

CASE PRESENTATION
A 66-year-old man presented to the emergency department with fever and a palpable skin rash on his forearms and hands (Figure 1).His system review and physical examination were both unremarkable.
An extensive rheumatological, hematological and infectious workup gave negative results, apart from mild anemia of 121 g/L and an eosinophil count of 2.51×10 9 /L.Abdominal computed tomography scan revealed retroperitoneal lymphadenopathy.A skin biopsy was performed and was interpreted as necrotic eosinophilic vasculitis.To rule out lymphoma, a diagnostic laparoscopy with an abdominal lymph node biopsy was performed which revealed a diffuse neutrophilic inflammation with abundant foamy macrophages, fat necrosis and lipogranuloma formation.These findings were considered to be nonspecific, and no further pathological investigation was carried out.
Subsequently, the patient was treated with corticosteroids, and the fever and rash resolved.One month after discharge, he returned with severe diarrhea and dehydration.Repeat workup was again unremarkable with the exception that an abdominal computed tomography scan revealed persistent lymphadenopathy.He was discharged after mild improvement of the diarrhea after being put on an empirical trial of metronidazole.He was readmitted one month later with persistent diarrhea and a 4.5 kg weight loss.Repeat investigations revealed worsening anemia with a hemoglobin level of 109 g/L, a normal mean corpuscular volume, and an erythrocyte sedimentation rate of 37 mm/h.His serum albumin level was 20 g/L but his liver profile was otherwise normal.His serum tissue transglutaminase antibody level was normal.He underwent a gastroscopy, and duodenal biopsies were obtained that revealed subtotal effacement of the intestinal villi with blunting as well as diffuse infiltration of the lamina propria by foamy macrophages (Figure 2).This histology was consistent with Whipple's disease and the diagnosis was confirmed by periodic acid-Schiff (PAS) staining which coarsely dyed the intracytoplasmic granules.At this time, the pathology of the abdominal lymph node was reinvestigated and the diagnosis of Whipple's disease involving the lymph node was made (Figure 3).It was confirmed by the PAS-positive reaction of the infiltrating macrophages in a fashion similar to the intestinal biopsy (Figure 4).
The patient was treated with a two-week course of intravenous ceftriaxone and later, trimethoprim and sulfamethoxazole (one double-strength tablet taken twice a day) were administered, with a plan to continue the treatment for one year.Within the first few weeks of treatment, his diarrhea resolved and he started gaining weight.

DISCUSSION
The typical clinical manifestations of Whipple's disease, namely diarrhea, weight loss and malabsorption, are present in the majority of patients at the time of diagnosis (3).However, these symptoms are usually preceded by a wide range of symptoms such as arthralgias and abdominal pain, and general systemic features such as fever and weight loss.Neurological and cardiovascular manifestations occur typically late in the course but have been described at the initial presentation in the absence of significant gastrointestinal complaints, making the diagnosis of this rare disease further challenging.
In the current case, the presentation was a vasculitic skin rash, fever and eosinophilia.Rarely has cutaneous manifestations been an early feature in this disease, and apart from five documented cases (6)(7)(8)(9)(10) in the literature of direct Whipple's involvement, cutaneous manifestations are generally nonspecific and related to malnutrition -hyperpigmentation, urticaria, erthythroderma and subcutaneous nodules.In the present case, cutaneous involvement with Whipple's disease was ruled out by re-examining the skin biopsy with PAS staining after Whipple's disease had been diagnosed.
We consider eosinophilic vasculitis to be a secondary manifestation of Whipple's disease.This is based on the temporal relationship between the appearance of the eosinophilic rash and the gastrointestinal symptoms, as well as the presence of eosinophils in the skin, small bowel and lymph nodes.
The diagnosis in the present case was delayed because of the unusual initial presentation leading to the workup directed toward a vasculitic process or a lymphoma.The correct diagnosis of Whipple's disease could have been reached earlier if it had been included in the differential diagnosis of abdominal lymphadenopathy and diarrhea.
Recently noninvasive testing using the polymerase chain reaction test for T whippelii has been introduced, and probably explains the increased incidence of this disease (2).Similarly, the presence of foamy macrophages has been described in many organs in patients with Whipple's disease.Such extraintestinal involvement is not well characterized and can be missed if the appropriate stains are not used, as in the present case.

CONCLUSION
Although rare, Whipple's disease should still be in the differential diagnosis of any unexplained digestive disease associated with intra-abdominal lymphadenopathy or systemic manifestations (Table 1).It is not uncommon that Whipple's disease has extraintestinal involvement (lymph nodes, liver, spleen, etc), so diagnostic suspicion should be heightened when an abundance of histiocytes accompanied by inflammatory infiltrates are seen.In such cases, a PAS stain or T whippelii polymerase chain reaction test should be considered.