Table 1.

Patients’ clinical features.

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
Imaging	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
Genetic test PHO	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.