Bệnh Kikuchi–Fujimoto Trình bày với Bệnh hạch bạch huyết mạc treo và Bệnh mô bào lympho thực bào máu ở một nam giới da đen trẻ tuổi

Abstract

Kikuchi–Fujimoto disease (KFD) is a rare, self-limited inflammatory condition that typically presents with cervical lymphadenopathy and constitutional symptoms, classically described in young Asian women. We report an atypical presentation in an 18-year-old Black man with weight loss, fevers, and isolated mesenteric lymphadenopathy, ultimately diagnosed with KFD by excisional biopsy. His presentation was also notable for mild secondary hemophagocytic lymphohistiocytosis (HLH). This case highlights an association between isolated mesenteric KFD and hemophagocytic lymphohistiocytosis, suggesting a spectrum of disease that links these syndromes.

Background

Kikuchi–Fujimoto disease (KFD) is a rare, generally benign and self-limited inflammatory condition typically characterized by fever, cervical lymphadenopathy, rash, myalgias, and night sweats. Although classically described in young Asian women, more recently, KFD has been reported in individuals of many ethnicities 1. Due to its rarity and nonspecific clinical features, KFD is often mistaken for lymphoma, systemic lupus erythematosus (SLE), infectious lymphadenitis, or other inflammatory conditions. Thus, diagnosis often requires an excisional lymph node biopsy 2.

Although viral triggers such as Epstein–Barr virus (EBV), parvovirus, and influenza have been implicated 3 and the disease is sometimes associated with SLE 2, the cause of KFD remains unknown. This case of KFD was atypical in presentation and complications, including its association with hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory syndrome characterized by multiorgan damage and usually triggered by infections, autoimmune conditions, or malignancy 4.

Case Report

An 18-year-old man with a history of asthma presented to the emergency department with a 3-week history of fatigue, anorexia, intermittent fevers, abdominal pain, night sweats, cough, and a 10- to 15-pound unintentional weight loss. Two weeks before presentation, he developed periorbital edema and was prescribed levofloxacin with subsequent resolution. He did not report dyspnea, gastrointestinal symptoms, arthralgias, myalgias, rashes, or sore throat. There were no other recent illnesses, travel, insect bites, or animal exposures. Family history was notable for multiple malignancies (pancreatic, ovarian, breast, and multiple myeloma) but no autoimmune conditions. He did not report smoking, alcohol, drug use, or sexual activity.

On presentation, he was tachycardic (110 beats/min) and febrile to 39.4 °C. His examination demonstrated mild epigastric tenderness without palpable lymphadenopathy or hepatosplenomegaly. Laboratory evaluation revealed normocytic anemia (hemoglobin level, 12.7 g/dL), leukopenia (leukocyte count, 3.0 × 103/μL; absolute neutrophil count, 2.4 × 103/μL; absolute lymphocyte count, 0.4 × 103/μL), and normal platelet count (243 × 103/μL). His creatinine level was elevated at 1.24 mg/dL (baseline, 0.8), urinalysis showed small proteinuria (without red or white blood cells or casts), and his urine protein-to-creatinine ratio was 170 mg/g. Infectious work-up, including respiratory viral panel, rapid streptococcal test, and monospot, was negative, though EBV IgG was positive (Table 1), suggesting prior EBV infection. An abdominal computed tomography scan identified a 3.9- × 3.0- × 6.5-cm mesenteric lymph node conglomerate (Figure 1).

Value outside the normal range.

Testing not repeated at the given time.

His constellation of leukopenia, lymphopenia, renal dysfunction, and lymphadenopathy initially prompted concern for SLE, with other inflammatory, infectious, and malignant conditions on the differential diagnosis, including lymphoma, tuberculosis, HLH, sarcoidosis, vasculitis, and arthropod-borne illnesses. Further work-up revealed a lactate dehydrogenase level of 837 U/L, a haptoglobin level of <8 mg/dL, a ferritin level of 8775 ng/mL, a C-reactive protein level of 41.9 mg/L, and an erythrocyte sedimentation rate of 37 mm/hr. His antinuclear antibody text was negative, with normal complement levels, which markedly decreased suspicion for SLE.

Bone marrow biopsy demonstrated increased foamy histiocytes with cytoplasmic debris but no definitive hemophagocytosis, interpreted as “low-level HLH” (Figure 2). Endoscopic ultrasound-guided lymph node biopsy yielded nondiagnostic necrotic tissue. Around this time, the patient reported transient bilateral hand arthralgias without synovitis. Despite absence of a clear infectious source, empirical treatment of ampicillin-sulbactam was initiated owing to persistent fevers and tachycardia.

An excisional lymph node biopsy revealed histiocytic and necrotizing lymphadenitis consistent with KFD (Figure 3). His inflammatory markers and symptoms improved during hospitalization and resolved with a short outpatient steroid taper. He remains clinically stable off steroids and is following up in the rheumatology clinic.

Discussion

This patient’s presentation included some hallmarks of KFD, including constitutional symptoms and arthralgias, but was atypical in other respects. As a young Black man, this patient’s demographic group was unusual for KFD, which has a female predominance in adults and a male predominance among children 5. He also presented with isolated mesenteric lymphadenopathy rather than cervical lymphadenopathy, which has been previously described in KFD though is uncommon 6, 7.

Most unique about his case was the concurrence of isolated mesenteric KFD with partial HLH, which has not been previously reported to the best of our knowledge. Based on the HLH 2024 diagnostic criteria, 5 of the following 7 criteria must be met to make the diagnosis: fever, splenomegaly, cytopenia in 2 or more specified cell lines, hypofibrinogenemia or hypertriglyceridemia, hyperferritinemia, hemophagocytosis, and elevated soluble CD25, also known as soluble IL-2 receptor α 8. The patient met 3 criteria: fever, hyperferritinemia, and elevated soluble IL-2 receptor α. He also had mild anemia and hypertriglyceridemia, though neither level met the HLH 2024 thresholds, as well as histiocytosis on bone marrow biopsy without definitive hemophagocytosis. Overall, this was interpreted as “partial” HLH. In patients with HLH secondary to KFD, the mainstay of treatment is corticosteroids and, occasionally, intravenous immunoglobulin 9. In our case, given the patient’s improvement during his admission and stability on a steroid taper directed at KFD, it was decided to not treat specifically for HLH.

Several reports have described KFD leading to secondary HLH 9, 10. In a review of these cases, all patients presented with cytopenias, increased ferritin, and increased lactate dehydrogenase levels, consistent with our case. While KFD is typically benign, secondary HLH can be a fatal complication due to multiorgan failure and/or disseminated intravascular coagulation 9. Hence, clinicians must remain vigilant regarding development of HLH in patients with KFD.

The cause of KFD and its connection to HLH remains unclear. However, given an increase in literature describing HLH secondary to KFD, it has also been proposed that the 2 conditions arise from a common source or represent a spectrum of disease 11, 12. In this case, the patient presented with certain features of HLH without full-blown disease, supporting the possibility that the conditions may lie on a continuum of immune dysregulation. Both KFD and HLH are associated with increased lymphocyte and histiocyte activation and may be triggered by infections or autoimmune disorders 1, 12. For instance, EBV has been associated with both conditions; it is the most common infection associated with HLH 4. Prior or current EBV infection has been identified in 35% of patients with infection-associated HLH secondary to KFD 13. Our patient had a positive EBV IgG, although the temporal relationship is unclear as we did not detect an IgM antibody to suggest acute infection.

Regarding the relationship between KFD and HLH and autoimmune disorders, both have been associated with SLE. Many patients with KFD ultimately develop SLE: of a review of 158 patients with KFD, 31% were eventually diagnosed with SLE 14. Systemic lupus erythematosus is also closely associated with HLH, with 4% of patients with SLE developing HLH 15. Together, these associations support the possibility that KFD, HLH, and SLE represent overlapping manifestations along a continuum of immune dysregulation.

This case underscores the importance of a systematic diagnostic approach, including tissue diagnosis, in patients with undifferentiated inflammatory syndromes. Although lymph node sampling in this patient required multiple attempts, excisional biopsy ultimately revealed features characteristic of KFD, which include well-circumscribed areas of necrosis with karyorrhectic nuclear debris and histiocytes 1. Early multidisciplinary involvement was essential in recognizing partial HLH and maintaining awareness of potential future development of SLE, highlighting the need to remain vigilant for secondary inflammatory processes in patients with KFD.