Table 1.
Hematological complications from systemic TNF blockade.
| Adverse effect | Diagnosis | Treatment | Brief report | Onset upon anti-TNF treatment | Reference | |
|---|---|---|---|---|---|---|
| Pancytopenia | Juvenile idiopathic arthritis | Etanercept | 2/61 cases | After 0,5-12 months | (46) | |
| Scleroderma | Infliximab | 45F case Previously diagnosed with anemia, ANA positive |
After 2 weeks | (47) | ||
| RA | Infliximab + MTX (Previously leflunomide) |
66M case BM hypoplasia |
After 10 days | (48) | ||
| Indeterminate colitis | Infliximab + antibiotics | 32F case | After 6 days | (49) | ||
| RA | Etanercept | 1/1073 case | NR | (50) | ||
| RA | Etanercept + MTX | 68F case | After 3 weeks | (51) | ||
| Aplastic anemia | RA | Etanercept | 78M case | After 16 weeks | (52) | |
| Thrombocytopenia | Psoriatic arthritis | Infliximab | 1/16 case | After 12 weeks | (53) | |
| Crohn’s disease | Infliximab | 15M case Platelet associated autoantibodies positive |
After 6 days | (54) | ||
| RA | Etanercept | 2/1073 cases | NR | (50) | ||
| RA | Etanercept | 44F case Autoantibodies negative |
After 1,5 weeks | (55) | ||
| RA | Infliximab + MTX | 56F case ANA positive dsDNA autoantibodies positive |
After 28 months | |||
| Scleroderma overlap/rheumatoid arthritis | MTX + Prednisone + Infliximab | 44F case Anticardiolipin antibodies positive ANA positive Anticentromere antibodies positive |
After 13 months | (56) | ||
| Crohn’s disease | Infliximab then Adalimumab (Previously metronidazole and azathioprine) |
42F case Platelet associated antibodies positive Increased BM megakaryocytes Anticardiolipin antibodies negative |
30 weeks after Infliximab treatment 1 week after Adalimumab treatment |
(57) | ||
| Psoriatic arthritis | Etanercept | 61M case Autoantibodies negative |
After 2 months | (58) | ||
| Psoriasis | Etanercept | 1/39 case ANA positive |
After 9 weeks | (59) | ||
| Psoriatic arthritis | Infliximab | 1/26 case Autoantibodies negative |
After 29 weeks | |||
| Psoriasis | Infliximab | 2/26 cases ANA positive Antiplatelet antibodies positive |
After 30 weeks | |||
| Crohn’s disease | Infliximab | 75M case | After 14 weeks | (60) | ||
| Ulcerative colitis | Adalimumab + azathioprine + mesalazine | 54F case Anemia Autoantibodies negative |
After 4 years | (61) | ||
| Thrombocytopenia and leucopenia | Juvenile idiopathic arthritis | Etanercept | 2/95 cases | NR | (62) | |
| Thrombocytopenia and neutropenia | RA | MTX + Infliximab | 60F case BM hypoplasia Autoantibodies negative |
After 7 weeks | (63) | |
| Bone marrow aplasia with pancytopenia | RA | Etanercept (Previously MTX + folic acid + Hydroxychloroquine; Leflunomide and Adalimumab discontinued months before Etanercept) |
62F case Autoantibodies negative |
After 23 days | (64) | |
| Neutropenia | RA | Etanercept | 1/208 case | NR | (53) | |
| RA | Etanercept | 2/207 cases | ||||
| Spondyloathropathy/Crohn’s disease | Infliximab | 20M case Neutrophil-associated antibodies |
After 4 weeks | (65) | ||
| RA | Adalimumab | 3/21 cases Adalimumab 13/75 cases Etanercept 3/23 cases Infliximab 7/65 cases ANA positive |
After 1 week – 26 months | (66) | ||
| Etanercept | ||||||
| Infliximab | ||||||
| RA | Adalimumab + MTX | 53F case T-cell lymphocytosis (large granular lymphocytes) |
After 13 months | (67) | ||
| Sacroiliitis | Salazopyrine + MTX + Etanercept | 37F case | After 6 months | (68) | ||
| RA | Etanercept (Previously MTX) |
57F case Asymptomatic neutropenia during MTX Increased BM immature granulocyte production ANA positive Neutrophil-associated antibodies negative |
After 7 weeks | (69) | ||
| Psoriatic arthritis | Etanercept (Previously MTX) |
61M case Persistent leucopenia Neutropenia during MTX Normal BM hematopoiesis ANA positive Neutrophil-associated antibodies negative |
NR | |||
| RA | Etanercept | 50F case Previous asymptomatic neutropenia Normal BM hematopoiesis ANA positive Neutrophil-associated antibodies negative |
After 17 days | |||
| RA | Adalimumab + MTX + Prednisone | 55F case ANA negative dsDNA antibodies negative |
After 1 month | (70) | ||
| RA | Adalimumab 6/31 Etanercept 49/267 Infliximab 14/69 |
56/298 cases | NR | (71) | ||
| Psoriatic arthritis | 7/31 case | |||||
| Ankylosing spondylitis | 6/38 cases | |||||
| RA | Etanercept + MTX | 64F case | After 2 weeks | (72) | ||
| Ankylosing spondylitis | Etanercept | 36M case | After 2 months | |||
| RA | Etanercept then Etanercept re-challenge then Adalimumab |
65M case | 3 months after Etanercept onset 2nd neutrophil drop after Etanercept re-challenge Modest neutrophil drop after Adalimumab treatment |
|||
| RA | Etanercept then Etanercept re-challenge then 2nd Etanercept re-challenge |
71F case | 6 months after Etanercept treatment 16 months after Etanercept re-challenge 8 weeks after 2nd Etanercept re-challenge |
|||
| RA | Etanercept (Previously hydroxychloroquine + prednisolone) |
42F case | After 4 injections | |||
| 75/235 Crohn’s disease 21/46 Ulcerative colitis |
Adalimumab Certolizumab Infliximab Golimumab + MTX/azathioprine/5-ASA |
58/157 cases Adalimumab 2/6 cases Certolizumab 36/117 cases Infliximab 0/1 Galimumab 1/5 + MTX 77/188 + azathioprine 37/65 + 5-ASA |
After 1 day – 6 years Median 1 year |
(73) | ||
| Neutropenia and leucopenia | Ankylosing spondylitis | Etanercept + butazolidine then Etanercept re-challenge then Infliximab |
50M case | 3 weeks after Etanercept treatment 3 weeks after Etanercept re-challenge After 2nd Infliximab infusion |
(74) | |
| Leucopenia | RA | Etanercept | 4/1073 cases | NR | (50) | |
| Myelodysplastic syndrome | RA | Etanercept | 1/1073 case | NR | (50) | |
| Lymphoma | NR | RA | Etanercept | 3/1073 cases | NR | (50) |
| Cutaneous T-cell lymphoma | Psoriatic arthritis | Etanercept | 69M case | Erythroderma after 18 months | (75) | |
| Systemic anaplastic large cell lymphoma (ALCL) | Crohn’s disease | Infliximab | 81F case | After 5 months | ||
| Chronic myeloid leukaemia (CML) | RA | Infliximab + MTX | 56F case | After 6 months | (76) | |
| 16 non-Hodgkin’s lymphomas 1 Hodgkin’s disease 1 Type B1 thymoma |
15/18 RA 2/18 Psoriatic arthritis 1/18 NS |
Etanercept 9/18 +MTX 4/18 prior MTX 4/18 prior other immunosuppressive drugs |
18 cases Median age 64 years 2 cases non-Hodgkin’s lymphoma recursion 1 case nodular sclerosing Hodgkin’s disease recursion |
After 2-52 weeks | (77) | |
| 5 non-Hodgkin’s lymphomas 3 Hodgkin’s lymphomas |
3/8 RA 5/8 Crohn’s disease |
Infliximab 2/8 +MTX 1/8 + 6‐mercaptopurine |
8 cases Median age 62 years |
After 2-44 weeks | ||
| Non-Hodgkin’s lymphomas Hodgkin’s lymphomas |
RA | Infliximab | 6/5233 cases | NR | (78) | |
| RA | Etanercept | 5/2149 cases | ||||
| Hodgkin-like lymphoproliferative disorder | Ulcerative colitis | Infliximab | 74M case | After 3 months | (79) | |
| 4 Hodgkin lymphomas 4 B-cell lymphomas 1 metastatic lymphoma |
Crohn’s disease | Infliximab | 9/1541 cases | NR | (80) | |
‘+’ treatments were taken concomitantly. ANA, anti-nuclear antibody; BM, bone marrow; MTX, methotrexate; NR, not reported; NS, not specified; RA, rheumatoid arthritis.