AITL is a rare aggressive lymphoma with a high mortality rate. AITL accounts for 1–2% of all cases of non-Hodgkin lymphoma (NHL), but more than 80% of cases are in advanced stages [1]. It occurs most commonly in men of middle age and older. The clinical presentation of AITL is variable, with B symptoms (fever, weight loss, and/or night sweats) and lymph node enlargement being the most common physical findings. Increased LDH, anemia, and hypergammaglobulinemia are present in most patients at some point [1, 2]. Cutaneous manifestations such as papules, erythema, petechiae/purpura, and urticarial, plaque-like or nodular eruptions in approximately 50% of AITL cases [3, 4].

The histopathology of AITL lesions is characterized by a perivascular infiltrate of small to medium-sized T cells. This may be accompanied by a mild epidermotropism, often with reactive histiocytes, plasma cells, and/or eosinophils. Due to differences in the tumor microenvironment, characteristic lymph node AITL changes such as atypical lymphocytes with clear cytoplasm, HEV hyperplasia, and scattered EBER-positive cells are present in few skin biopsies. Although the diagnostic criteria for lymph node AITL do not apply exclusively to the cutaneous site, the presence of pathologic changes similar to those seen in lymph nodes in cutaneous lesions may suggest the diagnosis.

The etiology and pathogenesis of AITL are unclear, most patients have a history of infections and medications before presentation, especially antibiotics, and specific infections such as Mycobacterium tuberculosis, Cryptococcus, and human herpesviruses can also be induced [5]. Relevant studies have shown that the pathogenesis of AITL is related to the abnormal proliferation of follicular helper T-cells (TFH). AITL originates from TFH and exhibits a variety of tumor microenvironment (TME) [6]. Mutant TFH cells enhanced the secretion of CXCL-13 and VEGF-1 and promoted the expansion and proliferation of follicular dendritic cells (FDCs) and high endothelial venules (HEVs), which are common in AITL [7]. In this case, elevated peripheral blood EBV-DNA, Epstein-Barr encoding region (EBER) in situ hybridization revealed EBER-positive nuclei in lymph nodes and abnormal expression of CXCL13-positive lymphocytes in skin tissue and lymph nodes were detected.

Angioedema is an edema of the skin and mucosal tissues caused primarily by vasodilatation of the deep dermis and subcutaneous tissues, allowing exudate to leak from the blood vessels into the loosened tissues to form a localized edema. The main symptom of angioedema is swelling, which usually occurs in the area of the face, mouth and upper respiratory tract. Histamine-mediated angioedema occurs through an allergic mechanism and is often accompanied by episodes of urticaria and swelling with severe pruritus, and symptoms usually resolve within 24 h [8]. Bradykinin-induced angioedema can be classified into hereditary angioedema (HAE), acquired angioedema, and angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema. Of these, acquired angioedema is a rare cutaneous manifestation of AITL associated with C1 esterase inhibitor (C1 INH) levels [9]. Angioedema without histamine or bradykinin involvement includes pseudoallergic angioedema (PAE) and idiopathic angioedema (IAE). PAE is a form of drug-induced nonallergic angioedema, such as allergic reactions to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), in which severe bronchoconstriction, severe laryngeal angioedema, urticaria, or shock occur within 3 to 4 h after ingestion of the drug [10, 11]. Although the patient had a history of aspirin use before the onset of his illness, he did not present with severe symptoms within a short period after taking the drug. In this case, the patient's blood level of C1 INH was not analyzed, but from the analysis of the clinical presentation and history, we believe that the patient is consistent with acquired angioedema. The primary symptoms were edema and dyspnea in the eyes and lips, which were alleviated by corticosteroid treatment, but the angioedema showed a recurring pattern, which was related to the patient's AITL disease progression. In addition, the patient's previous diagnosis of myocardial infarction due to shortness of breath and wheezing was likely the time of the most initial presentation of the patient's AITL symptoms.

Currently, CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) chemotherapy regimens are the standard of care for AITL. The efficacy of these regimens can be improved with various therapeutic approaches. The disappointing results of first-line therapies underscore the urgent need for new therapeutic options. Stratified diagnosis and treatment based on sensitivity to targeted agents such as histone deacetylase inhibitors, hypomethylating agents, and anti-CD30 therapy are expected to improve the prognosis of AITL patients [12].

AITL is a rare form of T-cell lymphoma, and its atypical and non-specific clinical presentation poses a challenge to its clinical diagnosis. With the development of precision medicine, researchers have investigated peripheral cell-free DNA (cfDNA) to identify the mutational characteristics of AITL, which provides great clinical value for liquid biopsy [12]. We describe a case in which the initial symptom (angioedema) was misleading. It is strongly recommended that angioedema of unknown origin be evaluated further.