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Background: Inflammatory lung disease (ILD) in Still’s disease (SD) has recently been described. Pulmonary arterial hypertension (PAH) is another rare and life-threatening associated event, with only a few case reports published.
Objectives: To report the largest cohort of PAH occurring in the context of SD.
Methods: We identified 16 adult SD patients with PAH (PAH+ group, PAH was confirmed by right heart catheterization in all patients) by a call for observations from the CRIIMIDIATE network and a search of the French PH network registry. Patient characteristics and disease evolution were retrospectively compared with those of 111 SD controls without PAH (PAH-) followed in a reference centre.
Results: The profile of patients in the PAH+ and PAH- groups differed (Table 1): 100% versus 69.4% female (p=0.006), 75% versus 17.1% Black (p<0.0001), more active SD both at diagnosis and throughout the disease course, and more likely to present MAS (62.5% vs 14.4%, p<0.0001), which was recurrent (i.e. ≥ 2 episodes) in most cases (7/10 patients), and exhibit eosinophilia during the disease course (68.7% vs 7.2%, p<0.0001). For the 84/127 patients with genetic typing, the HLA-DRB1*15 allele was more prevalent in PAH+ than PAH- patients (8/11 [72.7%] vs 22/51 [30.1%], p=0.014). The groups did not differ in treatment, except for methotrexate (81.2% vs 50.4%, p=0.029), canakinumab (50% vs 21.6%, p=0.026) or immunosuppressant agents (56.2% vs 10.8%, p<0.0001) that were more often used in the PAH+ group, reflecting a more active underlying SD. There was higher frequency of drug reactions to interleukin 1 (IL-1) and/or IL-6 inhibitors in PAH+ than PAH- patients (37.5% vs 7.2%, p=0.002). Mortality was higher in PAH+ than PAH- patients (37.5% vs 0.9%, p<0.0001), all deaths related to SD flare.
Conclusion: PAH is a specific manifestation, different from SD-related lung disease, but develops on the same background (i.e., in patients with MAS, especially when recurrent, eosinophilia and carrying the HLA-DRB1*15 allele). The proximity between PAH and LD in SD reinforces the association of the HLA-DRB1*15 allele with severe forms of SD and raises the question of treatment optimisations to better control both SD and its complications.
REFERENCES: NIL.
Characteristics of Still’s disease patients with and without pulmonary arterial hypertension (PAH)
| Still’s disease with PAH
| Still’s disease without PAH
| p-value
|
|
|---|---|---|---|
| Decade of Still’s disease onset 1 , n (% ) | |||
| ≥ 2010 | 13 (81.3) | 88 (79.3) | 1 |
| Female, n (% ) | 16 (100) | 77 (69.4) | 0.006 |
| Ethnicity, n (% ) | |||
| Caucasian | 3 (18.7) | 64 (57.7) | < 0.0001 |
| Black | 12 (75.0) | 19 (17.1) | |
| Others (Asian, North Africa, Middle East) | 1 (6.3) | 28 (25.2) | |
| Age at Still’s disease onset 1 , median (IQR ) | 25 (21–36) | 27 (20–37) | 0.982 |
|
Modified Pouchot score at Still’s disease diagnosis
| (data available for 15 patients)
| (data available for 67 patients)
|
|
| Still’s disease manifestations (ever during disease course), n (% ) | |||
| Fever | 16 (100) | 110 (99.1) | 1 |
| Rash | 16 (100) | 99 (89.2) | 1 |
| Arthralgia/arthritis | 15 (93.7) | 107 (96.4) | 0.495 |
| Odynophagia | 14 (87.5) | 77 (69.4) | 0.233 |
| Myalgia | 13 (81.2) | 47 (42.3) | 0.005 |
| Lymphadenopathy | 16 (100) | 49 (44.1) | < 0.0001 |
| Hepatomegaly and/or abnormal liver tests | 16 (100) | 54 (48.7) | < 0.0001 |
| Acute hepatitis with transaminases ≥10 N | 7 (43.7) | 20 (18.0) | 0.043 |
| Splenomegaly | 11 (68.7) | 15 (13.5) | <0.0001 |
| Pericarditis | 12 (75.0) | 16 (14.4) | <0.0001 |
| Pleuritis | 5 (31.2) | 9 (8.1) | 0.017 |
| Myocarditis 2 | 4 (25.0) | 10 (9.0) | 0.063 |
| MAS
3
| 10 (62.5) | 16 (14.4) | <0.0001 |
|
Eosinophilia ever during disease course, n (%
)
4
| 11 (68.7)
| 8 (7.2)
|
<0.0001
|
|
HLA-DRB1*15-positive, n/N available (%
)
| 8/11 (72.7) | 22/73 (30.1) | 0.014 |
|
| |||
| Glucocorticoids, n (% ) | 16 (100) | 108 (97.3) | 1 |
| Methotrexate | 13 (81.2) | 56 (50.4) | 0.029 |
| IL-1 and/or IL-6 blockade, n (% ) | 16 (100) | 83 (74.7) | 0.021 |
| IL-1 inhibitor
|
|
|
|
| IL-6 inhibitor | 8 (50.0) | 45 (40.5) | 0.589 |
| Immunosuppressants, n (% ) | |||
| Ciclosporin | 5 (31.2) | 4 (3.6) | 0.001 |
| Azathioprine | 3 (18.7) | 2 (1.8) | 0.014 |
| Cyclophosphamide | 2 (12.5) | 0 (0) | 0.014 |
| Etoposide | 2 (12.5) | 1 (0.9) | 0.041 |
| JAK inhibitors, n (% ) | 3 (18.7) | 6 (5.4) | 0.086 |
| History of drug reactions to IL-1 or IL-6 inhibitors 6 , n (% ) | 6 (37.5) | 8 (7.2) | 0.002 |
| Deaths directly attributed to Still’s disease complications, n (% ) | 6 (37.5) | 1 (0.9) | <0.0001 |
In some patients, the disease developed in childhood (systemic juvenile idiopathic arthritis), but symptoms persisted and/or recurred in adulthood.
Including one patient with PAH in whom myocarditis developed in the context of major eosinophilia up to 8,000/mm 3 .
Among the population with PAH, 7 patients had multiple (≥2) episodes of MAS, and 1 had a refractory episode of MAS over several months associated with uncontrolled PAH that led to death.
Eosinophilia was defined as absolute eosinophil count ≥ 700/mm 3 or eosinophils ≥10% of the total white blood cell count, measured on at least two occasion.
Some patients had several lines of treatment.
Drug reactions to IL-1 and/or IL-6 inhibitors were all confirmed by a dermatologist and/or an allergologist, and included rashes atypical for SD (e.g. nonevanescent, pruritic, urticarial, a fortiori in the presence of blood eosinophilia), or acute reactions (respiratory distress, swelling or Quincke edema during or near the time of medication administration). Two patients in the PAH+ group met the criteria for DRESS syndrome (RegiSCAR ≥ 4). Local reactions at the injection site were not included in this category.
IL, interleukin–IQR, interquartile range–JAK, Janus kinase–MAS, macrophage activation syndrome–PAH, pulmonary arterial hypertension–10N, 10 times above normal
Acknowledgements: The authors thank the CRIIMIDIATE clinical research network (
Disclosure of Interests: None declared.
© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (