“A Dangerous Black Box:” Idiopathic Hemophagocytic Lymphohistiocytosis in Adult Patients—A Case Report and Review of the Literature

Table 4

Performed investigations to exclude infections, malignancies, rheumatic conditions, and genetic mutations.

Causes	Investigations	Results
Infections	Blood culture	Sterile
	Lumbar puncture	Sterile
	Transthoracic echocardiography	No vegetations
	QuantiFERON test	Negative
	SARS-CoV-2 PCR, SARS-CoV-2 spike antibodies, influenza PCR	Negative
	Viral serology (EBV, CMV, HIV, HAV, HBV, HCV, HDV, HEV, HHV6, parvovirus B19, Bartonella, leptospirosis, toxoplasmosis, Coxiella)	Negative
Malignancies	Thorax X-ray, abdominal ultrasound, CT of the thorax, abdomen, and pelvis	No suspected lesions
	Bone marrow biopsy, skin biopsy, liver biopsy	No malignancy
	PET-CT	Metabolic active lesions:
		1. Right knee
		2. Colon ascendants and sigma
	Right knee MRI	Pigmented villonodular synovitis (PVNS), nonmalignant
	Gastroscopy and colonoscopy	No malignancy
Rheumatic conditions	ANA, Hep2 cytoplasmic, SsA, PR3-ANCA, MPO-ANCA	Negative
	Rheumatic disease symptoms	None
Genetic causes	Genes PRF1, STX11, STXBP2, UNC13D	No pathologic variant

Polymerase chain reaction (PCR), Epstein–Barr virus (EBV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), hepatitis E virus (HEV), human herpes virus 6 (HHV6), computed tomography (CT), positron emission tomography-computed tomography (PEC-CT), magnetic resonance imaging (MRI), antinuclear antibodies (ANAs), antineutrophil cytoplasmic antibodies (ANCAs), myeloperoxidase (MPO), perforin 1 (PRF1), syntaxin 11 (STX11), syntaxin binding protein 2 (STXBP2).