Supplemental Table 1. Baseline characteristics of patients with fever of unknown origin (FUO) in the Divisions of Infectious Diseases and General Medicine

Wang et al. 1

Supplemental Table 1. Baseline characteristics of patients with fever of unknown origin (FUO) in the Divisions of Infectious Diseases and General Medicine

Characteristics

Training cohort Validation cohort P value^a FUO from the division

of ID (n = 85)

FUO from the division of GM

(n = 20)

Age (years) 62 (19–94) 60 (22–84) 0.717

Sex – males (%) 67 60 0.554

Interval between admission and bone marrow studies (days)

15 (1–107) 10 (1–41) 0.183

WBC, /µL (4000–11,000/µL)^b 9779 (1080–34,400) 9366 (1600–30,300) 0.825 ANC, /µL (2000–5500/µL)^b 7431 (570–31,992) 7252 (803–26,967) 0.916

Hb, g/dL 10.6 (5.6–18.3) 10.3 (7.7–12.2) 0.500

PLT, × 10³/µL (150–400 × 10³/µL)^b 216 (19–1270) 227 (51–560) 0.829 LDH, IU/L (131–250 IU/L^)b 587 (86–6100) 468 (139–1879) 0.522 IgG, mg/dL (751–1560 mg/dL)^b 1420 (404–3533) 1534 (623–3352) 0.488 Ferritin, ng/mL (4–274 ng/mL)^b 3873 (36–40,015) 2325 (113–13,441) 0.398 CRP, mg/dL (<0.5 mg/dL)^b 9.20 (0.05–36.40) 11.59 (0.69–45.10) 0.256

Lymphadenopathy, no. (%) 16 (19%) 6 (30%) 0.244

Splenomegaly, no. (%) 25 (29%) 3 (15%) 0.201

Hepatomegaly, no. (%) 3 (4%) 2 (10%) 0.212

PB smear with leucoerythroblastic changes, no. (%)

11 (13%) 1 (5%) 0.320

ANC, absolute neutrophil count; CRP, C-Reactive Protein; Hb, haemoglobin; IgG, immunoglobulin G; LDH, lactic dehydrogenase; PB, peripheral blood; PLT, platelet;

WBC, white blood cell.

a

t-test for quantitative data; Χ

²

test and the Fisher exact test for categorical data.

b

normal levels.

Wang et al. 1

Supplemental Table 2. Final diagnosis of 38 patients from the Division of Infectious Disease with diagnostic bone marrow biopsies

Final diagnosis Patients no (%)

Haematological aetiologies 29 76.3%)

Non-Hodgkin’s disease 15

B-cell immunophenotype 10

Diffuse large cell lymphoma 7

Burkitt’s lymphoma 2

Intravascular B-cell lymphoma 1

T-cell immunophenotype 5

Peripheral T-cell lymphoma 1

Subcutaneous panniculitic T-cell lymphoma 1

Nasal NK/T cell lymphoma 1

Angioimmunoblastic T-cell lymphoma 1

Unclassified 1

Hodgkin’s disease 2

Acute myeloid leukaemia 5

Myeloproliferative neoplasms 2

Myelofibrosis 1

Chronic myelomonocytic leukaemia 1

Myelodysplastic syndrome 1

Haemophagcytic syndrome 3

Monoclonal gammopathy of undetermined significance 1

Non-haematological aetiologies 9 (23.7%)

Acid-fast stain positive granuloma in BMB 1

Only granuloma in the BMB 8

Tuberculosis bacteria isolated from other tissues 2 Non-tuberculosis mycobacteria isolated from other tissues 1 Response to anti-tuberculosis treatment without mycobacterial isolation 2

Sarcoidosis 1

Granuloma disease 2

Wang et al. 1

Supplemental Table 3. Final diagnosis of 47 patients from the Division of Infectious Diseases with a non-diagnostic bone marrow biopsy

Final diagnosis of 47 patients from the Division of Infectious Diseases with non-diagnostic bone marrow biopsies

Patients, No. (%)

Infection 16 (34.0%)

Extra-pulmonary tuberculosis 3

Pulmonary tuberculosis 1

Nontuberculous mycobacteria 2

Sepsis 4

Septic arthritis 2

Soft tissue infection 1

Fungemia 1

Acute cytomegalovirus infection 1

Selective Immunoglobulin A deficiency with recurrent infection 1

Noninfectious inflammatory diseases 7 (14.9%)

Adult-onset Still’s disease 4

Systemic lupus erythematosus 2

Anti-neutrophil cytoplasmic antibody-associated vasculitis 1

Oncology 3 (6.4%)

Malignant pleural effusion

(adenocarcinoma of unknown origin)

1

Malignancy of unknown origin with multiple bone metastasis 1

Papillary microcarcinoma of thyroid gland 1

Haematology 2 (4.3%)

Hodgkin’s disease 1

Splenic lymphoma 1

Miscellaneous 3 (6.4%)

Hypersensitivity pneumonitis 1

Kikuchi’s disease 1

Sweet’s syndrome 1

No diagnosis 16 (34.0%)

Wang et al. 1

Supplemental Table 4. Predictive model using six factors

Items Findings Points

Absolute neutrophil count <2000/µL 1.0

Haemoglobin <10 g /dL 1.5

Lactic dehydrogenase >Upper normal limit 1.5

Platelets <100 × 10³/µL 2.0

Splenomegaly Yes 4.0

Ferritin >1000 ng/mL 5.5

Wang et al. 1

Supplemental Table 5. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of the scoring system with six or seven factors

Scoring system Total score = 6

AUC (95% Confidence interval) Sensitivity Specificity Six factors (No PB

smear)

0.82 0.71–0.92 0.83 0.58

Seven factors (including PB smear)

0.89 0.81–0.97 0.93 0.58

PB, peripheral blood

Wang et al. 1

Supplemental Table 6.

Bone marrow (BM) Score and final diagnosis of fever of unknown origin patients from the Division of General Medicine

Score BM yield Final diagnosis

18.0 Yes Acute myeloid leukaemia 14.5 Yes NK/T-cell lymphoma 10.0 Yes Burkitt’s lymphoma

9.5 Yes Diffuse large B cell lymphoma 9.0 Yes Myelodysplastic syndrome 8.5 Yes Myelodysplastic syndrome 7.0 Yes Diffuse large B-cell lymphoma 9.0 No Systemic lupus erythematosus

8.0 No No diagnosis

7.0 No Adult Still’s disease 5.5 No Gouty arthritis

3.0 No Diffuse large B-cell lymphoma 2.0 No Sweet's syndrome

1.5 No Subacute thyroiditis

1.5 No Sepsis

1.5 No Kawasaki disease, adult type 1.5 No Drug fever (Rabeprazole)

0 No Drug fever (Glucobay) 0 No Aseptic meningitis

0 No No diagnosis