Tuberculosis-associated hemophagocytic lymphohistiocytosis misdiagnosed as systemic lupus erythematosus: A case report

Table 1 Relative weights of the additive classification criteria items (with antinuclear antibody positivity as the entry criterion)

Domain	Item	Our case	Relative weights
Constitutional	Fever	39.7°C	2
Hematological	Leukopenia	1.28 x 109/L	3
	Thrombocytopenia	64 x 109/L	4
	Autoimmune hemolysis	N	4
Neuropsychiatric	Delirium	N	2
	Psychosis	N	3
	Seizure	N	5
Mucocutaneous	Alopecia	N	2
	Oral ulcers	N	2
	Subacute cutaneous or discoid lupus	N	4
	Acute cutaneous lupus	N	6
Serosal	Effusion	CT scan revealed pleural effusion	5
	Acute pericarditis	N	6
Musculoskeletal	Joint involvement	N	6
Renal	Proteinuria	Proteinuria (1.15 g/24 h)	4
	Class II/V	N	8
	Class III/IV	N	10
APL antibodies	Anti-phospholipid antibodies	APL antibodies were positive	2
Complements	C3 or C4 low	C3 level was reduced (0.50 g/L)	3
	C3 and C4 low	N	4
SLE-specific antibodies	Anti-Sm	Sm antibodies were positive	6
	Anti-dsDNA	N	6

The patient’s systemic lupus erythematosus (SLE) classification score was 26 according to the 2019 EULAR/ACR classification criteria. SLE can be diagnosed based on a score of 10 or more if the entry criterion is fulfilled. SLE: Systemic lupus erythematosus.

Table 2 Diagnostic criteria for hemophagocytic lymphohistiocytosis

A diagnosis of HLH can be made if either 1 or 2 is met	Our case
1. Molecular diagnosis consistent with HLH (e.g., pathologic mutations of PRF1, UNC13D or STX11)	N
2. Clinical and laboratory criteria (at least 5/8 should be fulfilled)	Y (5/8)
Fever ≥ 38.5°C	Y (39.7°C)
Splenomegaly	N
Cytopenia ≥ 2-3 cell lines in peripheral blood (hemoglobin < 90 g/L, platelets < 100 x 109/L, neutrophils < 1.0 x 109/L)	Y (hemoglobin 53 g/L, platelets 64 x 109/L)
Hypertriglyceridemia (fasting triglycerides > 265 mg/dL) and/or hypofibrinogenemia (fibrinogen < 150 mg/dL)	Y (fibrinogen 1.26 g/L)
Reduced or absent NK cell activity	N
Hemophagocytosis in bone marrow, spleen, CSF or lymph nodes	Y (hemophagocytosis in bone marrow)
Ferritin ≥ 500 mg/L	Y (ferritin 679.93 ng/mL)
Elevated soluble CD 25	N

HLH: Hemophagocytic lymphohistiocytosis.

Table 3 The HScore system

Parameter	No. of points (criteria forscoring)	Our case
Known underlyingImmunosuppression1	0 (no) or 18 (yes)	Yes (steroid therapy): 18
Temperature (°C)	0 (< 38.4), 33 (38.4–39.4), or 49 (> 39.4)	Temperature > 39.4°C: 49
Organomegaly	0 (no), 23 (hepatomegaly or splenomegaly), or 38 (hepatomegaly and splenomegaly)	No: 0
No. of cell lines involved in cytopenia2	0 (1 lineage), 24 (2 lineages), or 34 (3 lineages)	2 lineages involved in cytopenia (HGB <90 g/L; platelet <100 × 109/L): 24
Ferritin (μg/L)	0 (< 2000), 35 (2000-6000), or 50 (> 6000)	Ferritin 679.93 ng/mL: 0
Triglyceride (mmol/L)	0 (< 1.5), 44 (1.5-4), or 64 (> 4)	Triglyceride 2.6 mmol/L: 44
Fibrinogen (g/L)	0 (> 2.5) or 30 (≤ 2.5)	Fibrinogen 1.26 g/L: 30
Aspartate aminotransferase (U/L)	0 (< 30) or 19 (≥ 30)	Aspartate aminotransferase 99 U/L: 19
Hemophagocytosis on bone marrow aspirate	0 (no) or 35 (yes)	Yes (hemophagocytosis on bone marrow aspirate): 35

¹HIV positive or receiving long-term immunosuppressive therapy (i.e., glucocorticoids, cyclosporine A, azathioprine).

²Defined as a hemoglobin level of 9.2 g/L and/or a leukocyte count ≤ 5 x 10⁹/L and/or a platelet count ≤ 110 x 10⁹/L.

Our patient had an HScore of 219 (steroid therapy: 18, temperature > 39.4°C: 49, 2 lineages involved in cytopenia: 24, TG level of 2.6 mmol/L: 44, FIB level of 1.26 g/L: 30, AST level of 99 U/L: 19, hemophagocytosis in bone marrow aspirate: 35), which is much higher than the threshold score of 169.