HSP is a multisystem IgA-mediated vasculitis with a self-limited course, which may affect the skin, joints, gastrointestinal tract and kidneys. A likely mechanism behind this involves a process by which the complexes of immunoglobulin A (IgA) and complement component 3 (C3) become deposited on arterioles, capillaries and venules, thus increasing their brittleness and permeability. This is followed by deposits on the skin, joints, gastrointestinal tract, kidneys and other organs, thus causing bleeding and other symptoms. Purpura, arthritis and abdominal pain are known as the ‘classic triad’ of HSP. HSP occurs more often in children than in adults. The outcome of HSP predominantly depends on the degree of renal involvement.
The diagnosis of HSP is based on the combination of the symptoms, as few other diseases cause the same symptoms together. The diagnostic criteria for HSP, according to the American College of Rheumatology, are palpable purpura, bowel angina, a patient age of ≤20 years and histological changes of leukocytoclastic vasculitis. A diagnosis of HSP is 87.1% sensitive and 87.7% specific when two or more of these criteria are present (7
). The present study patient had palpable purpura of the lower extremities and buttocks combined with bowel angina, thereby meeting the American College of Rheumatology criteria for the diagnosis of HSP. Additionally, the patient had arthritis and hematuria and an increased serum IgA, which provided further support for the diagnosis of HSP.
The exact etiology of HSP is unknown, but factors including bacterial infection or drugs, foods, allergens (8
) and autoimmune connective tissue disease (9
) have been documented. In the literature, associations between solid organ malignancies and HSP have been reported in cases when there were no known triggering factors (11
). Several studies have reported the correlation between HSP and malignancies, including esophageal, lung, breast, gastric and prostate cancer, and hematological malignancies (11
). Solid tumors are more common than hematological malignancies in association with HSP (15
). Lung cancer is the most common solid malignancy associated with HSP. In the study by Zurada et al
), 3l patients with HSP had underlying malignancies, among which solid tumors accounted for 61% and lung cancer accounted for 25%. To the best of our knowledge, 13 cases of HSP associated with lung cancer have been reported to date () (16
). In these 13 cases there were 12 male patients and one female patient with an average age of 65.7 years (50–79 years). These cases included 8 diagnoses of squamous cell carcinoma, 3 of adenocarcinoma and 2 of small cell lung cancer. In 6 cases, the onset of the HSP and lung cancer processes was synchronous. In 6 cases, HSP preceded lung cancer and in 1 case HSP occurred after lung cancer had been diagnosed. All 13 patients exhibited skin and kidney involvement, 7 patients had gastrointestinal symptoms and 9 patients had joint involvement. These studies aided in the confirmation of the correlation between lung cancer and HSP. The patient in the present study had no correlation with these pathogenic factors. The onset of HSP occurred 14 days after surgical resection, making it likely that the HSP was associated with the lung cancer.
Characteristics of patients with Henoch-Schönlein purpura (HSP) associated with lung cancer.
In the 13 literature cases, the treatment for HSP ranged from oral steroids to a combination of intravenous methylprednisolone followed by prednisone. Other possible regimens include steroids/azathioprine, and intravenous immunoglobulin (IVIG). Although an explicit treatment for HSP associated with lung cancer has not been identified, several studies have presented a treatment for HSP associated with lung cancer. The lung cancer therapies induced a complete remission of HSP in 4 cases (16
) while steroid hormones were required for an improvement in HSP in another 6 patients (18
). Only one case (18
) reported a recurrence of HSP. The patient in the present study initially received prednisolone and methylprednisolone pulses combined with cyclophosphamide. This treatment achieved a partial remission of the HSP with the proteinuria decreased to 668.25 mg/24 h. Following this, a total of 4 cycles of chemotherapy were performed to treat the left lung metastasis. Complete remission of the HSP was achieved, suggesting that the treatment for malignancy may contribute to a complete remission of HSP.
The exact correlation between HSP and malignancies remains somewhat unclear. It is possible that malignancies and HSP in patients may be correlated with the generation and expression of tumor-associated antigens. These antigens, as heterologous material, are able to stimulate the body to produce aberrant antibodies. These antibodies react to antigens and lead to the resultant immune complex deposition within vessel walls. Moreover, tumor-associated antigens reduce the clearance of circulating immune complexes (28
). In addition, tumor-associated antigens may cause dysfunctionality in lymphocytes and lead to the immunoglobulin subtypes shifting from IgM to IgA,. Once this happens, a large number of inflammatory cytokines may be released and vascular inflammation may eventually occur (30
). The treatment of malignant tumors may also cause the occurrence of HSP. It is possible that radiotherapy, chemotherapy and surgical resection change the surface antigens of tumor cells or that tumor-associated antigens are released within the tumor cells following their destruction (31
). It has previously been demonstrated that numerous chemotherapeutic agents, including erlotinib (32
), cytarabine (33
) and anastrozole (34
), result in HSP.
The patient in the present study developed HSP following surgical resection, however, the exact nature of the correlation between HSP and lung cancer in this case remains poorly defined. The patient did not receive any medication and no known food allergens were consumed. It was therefore postulated that the occurrence of HSP in this patient may have been attributed to the malignancy itself. We suggest that the tumor-associated antigen may have changed or that there may have been internal antigen exposure to the blood circulation during surgical resection, thus leading to the occurrence of HSP.
The present study presents a rare case of HSP associated with small cell lung cancer. To the best of our knowledge, this case is only the third patient with HSP presenting with small cell lung cancer. In addition, this appears to be the only case of HSP occurring post-surgery. Although the present study only involved 1 case, a review of the literature also aided in the confirmation of a correlation between lung cancer and HSP. The present study also suggested that the tumor-associated antigen may change in the treatment process of cancer and lead to the occurrence of HSP. The specific mechanisms by which this occurs will require further research in the future. It remains unclear which is the most efficient treatment for HSP associated with malignant tumors, and since corticosteroid therapy may not cause complete remission, future anti-tumor therapies may play a more crucial role in the treatment of such patients.