The first patient was a 48-year-old Caucasian male with progressive and unintended weight loss, daily diarrhoea (initially without bleeding), and fever.
In the past medical history, he had a previous diagnosis of seronegative spondyloarthritis because of 7-year intermittent joint swelling, early morning stiffness associated with inflammatory back pain and increased C-reactive protein (CRP), and a familiar history of psoriasis. No history of travel or surgery was recorded. Therapeutic trials with different antirheumatic drugs included methotrexate, hydroxychloroquine, etanercept (ETN), and finally, tocilizumab (TCZ).
The most recent medical history of the first patient was characterized by disease relapse with fever and systemic inflammation (CRP 20 mg/l) without any response to a medium dose of glucocorticoids in May 2017. Before May 2017, he was finally treated with monthly TCZ 8 mg/kg intravenously, which was effective on his clinical manifestations, allowing the resolution of arthritis, and fever and led to normalization of CRP within 3 months of therapy and, notably, lasting 2 years. In April 2017, abdominal pain, daily fever (around 38 C), and daily diarrhoea without bleeding started. The patient reported a relevant weight loss of 8 kg during the last 3 months.
Importantly, physical examination showed no evidence of an arthritis flare, while cutaneous lesions on the lower limbs that may resemble a cutaneous vasculitis or atypical psoriasis. Laboratory exams revealed CRP 72 mg/l, hemoglobin 10.7 g/l, HLA-B38 positive, and HLA-B27 and B51 negative. Rheumatoid factor (RF), anticitrullinated protein antibodies (ACPAs), ANA, and ANCA autoantibodies were negative. The day after the admission in our hospital ward, the patient presented bloody diarrhoea with a significant decrease in the hemoglobin level in 24 hours (from 10.7 g/dl to 8.4 g/dl). Thus, he urgently underwent colonoscopy and gastrointestinal arteriography, but without revealing the site of bleeding.
We tested also Vidal-Wright reaction, CMV, HBV, HCV, H. pylori, TB test, rotavirus, adenovirus, norovirus, Yersinia, Shigella, Salmonella, Campylobacter, Clostridium, and blood cultures, but all tests resulted negative.
Suspecting an intestinal vasculitis or a chronic inflammatory bowel disease, we administered methylprednisolone 1 g daily for three days with the regression of diarrhoea and fever. In order to find the site of bleeding, he underwent a gastrointestinal bleeding scintigraphy and CT-PET, which revealed a diffuse uptake in the small bowel.
Because of persistent weight loss, we introduced parenteral nutrition and explored other causes of malabsorption syndrome, such as WD; thus, the patient underwent gastroscopy. The histological findings resulted in PAS-positive granules in macrophages (intestinal lipodystrophy) (Figure 1). T. whipplei was then detected in blood, feces, and saliva samples by PCR in an international reference laboratory.
Intravenous ceftriaxone (2 g daily for one week) was started followed by trimethoprim-sulfamethoxazole 160/800 mg 3 times a day with dramatic improvement. There were no relapses after 6 months and was a significant weight recovery (Figures 2 and 3).