In 1907, it was first reported by Whipple. In 1949, Black-Schaffer used PAS staining to discover PAS-positive substances in the macrophages of the small intestinal mucosa of patients. By 1960, Cohen and others conducted electron microscopy studies and concluded that the sickle-shaped granules in macrophages were composed of bacteria; the pathogen was rod-shaped, with a width of 0.2 μm and a length of 1.5–2.5 μm, named Whipple's bacillus. The pathogen enters through the mouth and can invade various organs throughout the body. After long-term antibiotic treatment, patients can recover, and the bacillus gradually disappears. Currently, it is believed that this disease is related to infection with Whipple's bacillus, but it has not yet been definitively identified, nor has an animal model been successfully developed.

bubble_chart Pathological Changes

The abdominal membrane is rough and dull. The small intestine is dilated, with thickened and rigid intestinal walls. The upper small intestine shows obvious inflammatory infiltration. The mesenteric membrane and surrounding lymph nodes in the abdominal cavity are enlarged, with a sieve-like appearance on the cut surface. The small intestinal mucosa appears grayish and scattered with yellow patches. Microscopically, the villi appear club-shaped, and macrophages are increased in the mucosa of the proximal small intestine, showing positive PAS staining with sickle-shaped granules. Under electron microscopy, these granules are composed of rod-shaped bacteria. Besides macrophages, these rod-shaped bacteria can also be widely found in small intestinal epithelial cells, lymphocytes, capillary endothelial cells, smooth muscle cells, polymorphonuclear granulocytes, plasma cells, and mast cells. In addition to the small intestinal mucosa, the bacteria can invade the heart, lungs, spleen, pancreas, esophagus, stomach, retroperitoneum, and systemic lymph nodes, indicating a systemic disease.

The most common symptom is chronic, multiple, recurrent arthritis or arthralgia. Before the onset of arthritis, some patients may already experience diarrhea, gradually developing steatorrhea with typical small intestine malabsorption symptoms. In rare cases, diarrhea may be absent, presenting only with abdominal pain and low-grade fever. Additionally, generalized lymphadenopathy may occur, with a few patients exhibiting splenomegaly.

bubble_chart Diagnosis

Long-term arthralgia accompanied by diarrhea, or simultaneous generalized lymphadenopathy, should raise suspicion of this disease. Diagnosis can be confirmed by impaired absorption in the xylose test, the presence of PAS-positive substances in small intestinal mucosal biopsy, and the identification of sickle-shaped particles under electron microscopy. It is important to exclude acquired immune deficiency syndrome (AIDS), macroglobulinemia, and systemic reticuloendothelial fungal diseases.

bubble_chart Treatment Measures

In the past, this disease was considered incurable. However, in recent years, research into its etiology and the use of antibiotic therapy have made it possible for patients to be cured and regain health.

In addition to general symptomatic treatment, the primary approach is antibiotic therapy. Procaine penicillin G 1.2 million units and streptomycin 1.0g are administered intramuscularly once daily for 10 to 14 days, followed by oral tetracycline 0.5g four times a day for several months. A treatment course that is too short may lead to relapse. After treatment begins, patients' symptoms improve and their weight increases, but complete symptom resolution may take months to years, with histological recovery being even slower. Other antibiotics such as chloramphenicol, ampicillin, doxycycline, and SMZ can also be used.