Clinical Features | Patient 1 | Patient 2 | Patient 3 | Patient 4 | |
---|---|---|---|---|---|
Sex | Male | Male | Female | Male | |
Age, yrs | Current | 20 | 21 | 15 | 5 |
At disease onset | 1.3 | 13 | 1 | 2 | |
At first observation | 2.2 | 13 | 9 | 2.5 | |
Clinical symptoms | Joint enlargement at onset | Knees, ankles, hands | Knees | Knees, back, ankles | Knees |
Developmental problems | Mild cognitive delay | Motor development and speech-language delay, ADHD, patent ductus arteriosus, delayed suture closure | |||
Dysmorphic features | Broad nasal bridge, mild hypertelorism, coarse facial features | Coarse facial features | Delay in suture closure, broad nasal bridge, coarse facial features | Plagiocephaly, abnormal eye slits, slightly dysplastic ears, not palpable left testicle | |
Skin abn | Pachydermia | Hyperhydrosis, seborrhea, cutis verticis gyrate, pachydermia | Hyperhydrosis, pachydermia | Hyperhydrosis | |
Hematological abn | Aplastic anemia, thrombocytopenia, splenomegaly, late-onset leukopenia | Anemia | |||
Digital clubbing | Watch-glass nails and clubbing | Watch-glass nails and clubbing | |||
Diagnosis | CRP, ESR | neg | neg | neg | neg |
ANA | neg | neg | neg | neg | |
Urine crystals | neg | neg | neg | neg | |
Test for MPS | neg | ||||
Bone marrow | Aplastic marrow with focal hematopoiesis, mainly erythropoiesis (less than 1%) | No abn | |||
PG* | x | x | |||
Imaging | Radiograph | no abn | no abn | Acro-osteolysis | Enlargement of the bone of the distal phalanges, thickening of the skull |
MRI | Aspecific enhancement of the periarticular soft tissue in the knees | Mild synovitis in the knees | Wrists and hands: no abn | Knees and skull: no abn | |
Genetic test PHO | HPGD | c.120delA + c.175_176delCT | c.120delA | c.175_176delCT + c.298T > C | |
SLCO2A1 | c.754C > T + c.794C > G | ||||
Further negative genetic tests | Karyotype, VCFS, and CACP genetics | FMR1 gene and CGH-array test | |||
Therapy** | Knee steroid injection | x | x | x | |
Synoviectomy | x | x | |||
NSAID | x | x | x | x | |
SSZ | x | x | |||
MTX | x | x | |||
Systemic steroid therapy | x | ||||
ETN | x | ||||
ADA | x |
↵* For prostaglandin dosage see Supplementary Table 1 (available online at jrheum.org).
↵** For dose and period of therapy, see the text. ADHD: attention deficit hyperactivity disorder; abn: abnormalities; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; neg: negative; ANA: antinuclear antibodies; MPS: mucopolisaccaridosis; PG: prostaglandin; MRI: magnetic resonance imaging; PHO: primary hypertrophic osteoarthropathy; VCFS: velo-cardio-facial syndrome; CACP: Camptodactyly-Arthropathy-Coxa vara-Pericarditis; CGH: comparative genomic hybridization; NSAID: nonsteroidal antiinflammatory; SSZ: sulfasalazine; MTX: methotrexate; ETN: etanercept; ADA: adalimumab.