BackgroundHypertrophic osteoarthropathy (HOA) is a syndrome characterized by abnormal proliferation of skin and periosteal tissues of the extremities. It can be a rare hereditary disease (pachydermoperiostosis) or can be secondary to various diseases, though mostly lung malignancies. Here, we report an unusual clinical presentation of HOA.Case presentationA 77-year-old man presented with fever, diarrhea, and an oligoarthritis involving the left knee and the ankles. Since left knee synovial fluid aspiration revealed an aseptic synovitis and Clostridium Difficile toxin was detectable in stool samples, a reactive arthritis secondary to a Clostridium Difficile induced colitis was initially suspected. However, the presence of a worsened digital clubbing and the lack of a good clinical response to steroid therapy led us to perform a radionuclide bone scanning, which revealed HOA. This turned out to be associated with a lepidic predominant lung adenocarcinoma, which was clinically and radiologically difficult to distinguish from a relapse of pneumonia.ConclusionConsistent with the literature, HOA tends to have a variable clinical presentation, mimicking that of various rheumatic diseases. This clinical case shows that HOA can present as a presumptive acute reactive arthritis, and it highlights the importance of patient’s follow-up in the differential diagnosis of inflammatory arthritis, especially when a worsened digital clubbing is present.

Background and Objectives: The “interstitial pneumonia with autoimmune features” (IPAF) criteria have been criticized because of the exclusion of usual interstitial pneumonia (UIP) patients with a single clinical or serological feature. To classify these patients, the term UIPAF was proposed. This study aims to describe clinical characteristics and predictive factors for progression of a cohort of interstitial lung disease (ILD) patients with at least one feature of autoimmunity, applying criteria for IPAF, specific connective tissue diseases (CTD), and a definition of UIPAF when possible. Methods: We retrospectively evaluated data on 133 consecutive patients with ILD at onset associated with at least one feature of autoimmunity, referred by pulmonologists to rheumatologists from March 2009 to March 2020. Patients received 33 (16.5–69.5) months of follow-up. Results: Among the 101 ILD patients included, 37 were diagnosed with IPAF, 53 with ILD-onset CTD, and 11 with UIPAF. IPAF patients had a lower prevalence of UIP pattern compared to CTD-ILD and UIPAF patients (10.8% vs. 32.1% vs. 100%, p < 0.01). During the follow-up, 4 IPAF (10.8%) and 2 UIPAF (18.2%) patients evolved into CTD-ILD. IPAF patients presented features not included in IPAF criteria, such as sicca syndrome (8.1%), and were more frequently affected by systemic hypertension (p < 0.01). Over one year, ILD progression (greater extent of fibrosis on HRCT and/or decline in PFTs) was less frequent in the IPAF group compared to CTD-ILD and UIPAF (32.3% vs. 58.8% vs. 72.7, p = 0.02). A UIP pattern and an IPAF predicted a faster (OR: 3.80, p = 0.01) and a slower (OR: 0.28, p = 0.02) ILD progression, respectively. Conclusions: IPAF criteria help identify patients who might develop a CTD-ILD, even though a single clinical or serological feature is respected. Future revisions of IPAF criteria should include sicca syndrome and separate UIP-pattern into a different definition (UIPAF), given its association with a different prognosis, independently from ILD classification.

Background:It is unknown whether patients with interstitial lung disease (ILD) and only some features of autoimmunity have a different natural history from those with a defined connective tissue disease (CTD-ILD). The classification criteria for “ILD with autoimmune features” (IPAF) may not be able to characterize all these patients, especially those with a usual interstitial pneumonia (UIP) pattern [1].Objectives:To determine clinical characteristics and predictive factors for progression in a cohort of ILD patients with features of autoimmunity, through the application of classification criteria for IPAF and specific CTD, whenever possible.Methods:We retrospectively selected a cohort of consecutive patients with ILD as onset manifestation and features of autoimmunity (at least 1 autoantibody and/or 1 clinical sign/symptom), evaluated by our multidisciplinary unit from March 2009 to March 2020. All the final diagnoses were revised according to the latest CTD and IPAF criteria. Patients were followed up for 33 (16.5-69.5) months.Results:Of the 101 patients enrolled (67.4±10.9 yrs, F/M ratio 65/36), 53 (52.5%) and 37 (36.6%) respectively satisfied the CTD and IPAF criteria. Eleven patients (10.9%) did not satisfy IPAF criteria because of only 1 item (clinical or serologic) within the IPAF domains and a UIP pattern; we defined this group as “autoimmune” UIP (AI-UIP). All the 8 patients initially classified as undifferentiated CTD had sufficient IPAF criteria. Among the IPAF patients (68.2±10.1 years, F/M ratio 20/17), the most common findings were: Nonspecific interstitial pneumonia pattern (56.8%), antinuclear antibodies positivity (43.2%) and arthritis (24.3%). The combination of a positive morphologic and serologic domain was the most common to reach the diagnosis (48.6%). Some IPAF patients had features not included in IPAF criteria, such as non-anti-synthetase myositis-specific antibodies (21.6%), objective sicca syndrome (13.5%) and anti-myeloperoxidase antibodies (2.7%). Over a median of 17 months, 2 IPAF patients (5.4%) developed a definite UIP pattern, while 4 (10.8%) a specific CTD. Comparing the IPAF, CTD-ILD and AI-UIP groups, no statistically significant differences were found in the mean age, sex distribution, smoking habits and mean duration of the disease. However, IPAF patients had a significantly higher prevalence of arterial hypertension and left-sided heart failure and a lower predominance of UIP pattern as expected (10.8% vs. 32.1% vs. 100%, p<0.01). Although no differences were found at the diagnosis, at 1 year the proportion of IPAF patients with radiological progression of the fibrosis and/or functional deterioration (defined by a decline in FVC of ≥ 10% and/or DLCO of ≥ 15% predicted) was lower to that of CTD-ILD and AI-UIP (17.1% vs. 31.4% vs. 63.6%, p 0.01). Fewer IPAF patients needed oxygen support (8.6% vs. 31.4% vs. 36.4, p 0.02). Considering the overall 101 patients, having an IPAF and a UIP pattern respectively predicted a slower (OR: 0.37, p 0.04) and a faster (OR: 3.56, p 0.01) ILD progression at the multivariate analysis.Conclusion:In our cohort, IPAF criteria were useful to identify a subset of patients with a slower ILD progression and a possible evolution to CTD (10-15% of cases) [2]. These criteria do not characterize all the patients with a UIP pattern and limited features of autoimmunity, which seem to have a worse prognosis, independently from the final diagnosis. Further studies are needed to clarify if the prognosis of AI-UIP is different from that of idiopathic pulmonary fibrosis.References:[1]Graney, et al. Ann Am Thorac Soc 2019;16(5):525-33.[2]Sebastiani, et al. Biomedicines 2021,9,17.Disclosure of Interests:None declared

Background:Endocrine and metabolic imbalance conditions can affect the development of subjective abnormal perceptions within fibromyalgia (FMR). In the case of autoimmune thyroid disease (ATD), prolonged, clinically active states of impaired glandular function may be associated with an FMR-type condition. Less clear is the association between subclinical or rapidly well-controlled states of thyroid disease and the presence of FMR, since this assessment, although analysed in some previous studies, was usually performed on cohorts of subjects where the absence of any other confusing factors was not well defined.Objectives:To evaluate the prevalence of subclinical autoimmune thyroid disease, or functionally controlled autoimmune thyroid disease, in a retrospective cohort of consecutively diagnosed patients suffering from fibromyalgia condition.Methods:Over a 2 years period of time (2018-2019) a monocentric joint evaluation was activated with the endocrinology section of our healthcare area in order to consecutively monitor the subjects belonging to both specialist clinics. Patients with ATD were not unfrequently firstly evaluated in the rheumatology ambulatory. Diagnosis of FMR was defined according to the American College of Rheumatology 2010/2011 criteria. At the same time, at the rheumatology clinics, all cases addressed with diagnosis of fatigue or chronic pain of no defined origin were analysed in order to carefully identify any associated, comorbidity problems. The diagnosis of ATD was confirmed according to recognized international criteria. The following results will focus on subjects with chronic Hashimoto type Thyroiditis (HT).Results:Among the HT patients, 98% were women, aged between 28 and 64. Over the 2 years considered period of time, 65 subjects suffering from HT, showing no active disease or unstable endocrine function were addressed to the rheumatology clinics owing to FMR related symptoms. Among them, 55 (84.6%) had a confirmed diagnosis of FMR. Within this time, we recognized 239 consecutive diagnoses of FMR in subjects aging 22-76 years, with a number of 114 found to be devoid of factors (other than ATD) able to be responsible for chronic pain, except for a modest component of situational anxiety, or mild mood depression, not requiring any specific drug intervention. Among the 114, so called “primary” FMR, 35.6% showed to suffer from TCH, under confirmed clinical/hormonal remission, or in a preclinical, early stage of onset. Within the 125 subjects, carrying a FMR condition related to previous or associated fostering pathology, 26.8% were positive for current or previous thyroid problems. The prevalence of TCH, in the “secondary” FMR conditions differed significantly (p<0.01) from that of other FMR promoting diseases (eg connective tissue diseases, such as Sjogren Syndrome), except for moderate-severe mood disorders and/or anxiety, and the most severe chronic osteoarthritis conditions, showing a confirmed secondary neuropathy.Conclusion:Although limited in number, the here reported data confirm the hypothesis of a significant association between ATD and FMR, even in subjects who were considered to be in a subclinical condition or in full clinical remission by the endocrinology colleagues. The physiopathology of this association needs further appropriate insights.Acknowledgements:We thank Dr Alberto Petterle for his previous helpful contributionDisclosure of Interests:None declared

Background:Interstitial lung disease (ILD) can be the first manifestation of connective tissue disease (CTD) and rheumatoid arthritis (RA). Pulmonologists are usually the first referral in these patients.Objectives:To determine: 1) the prevalence of ILD as initial manifestation of CTD or RA 2) clinical characteristics of such patients.Methods:From a database of consecutive patients with CTD or RA referred to our academic hospital from 2009 and 2017, we selected all the patients with ILD as initial manifestation of the disease. Periodic multidisciplinary evaluations were performed during a median follow-up of 48 (35-50) months.Results:1) Fifty-four of the 427 patients with CTD or RA (12.6%) had ILD as initial manifestation (mean age: 63.9±12.9 yrs, F/M ratio: 20/34). Autoimmune myositis was diagnosed in 16/54 patients (29.6%), systemic sclerosis in 11 patients (20.4%), RA in 9 patients (16.7%), Sjogren syndrome in 9 patients (16.7%) and SLE in 3 patients (5.5%). Six patients remained classified as IPAF (11.1%). Among the Rheumatology patients we followed-up in the same period, autoimmune myositis had the highest prevalence of ILD as initial manifestation (63.6%), followed by Sjogren syndrome (20.5%), systemic sclerosis (20.0%), RA (3.4%), and SLE (3.3%). 2) Patients with initial ILD were all firstly evaluated by the Pulmonologist and the main reasons for Rheumatology referral were positivity for one or more autoantibodies (57.4%), mainly ANA≥1:320, and joint pain (29.6%). Thirty-six patients (66.7%) received steroid and/or immunosuppressive therapy in the six months before the first Rheumatology visit to relieve respiratory symptoms. Twenty of these patients (58.8%) had rheumatic manifestations during steroid tapering. ILD CT patterns were NSIP (25 patients, 52.1%), UIP (18 patients, 33.4%), and organizing pneumonia (5 patients, 9.3%). In four patients (4.5%), autoantibodies became positive during the follow-up. The final diagnosis of CTD- or RA-ILD was made after a median period of 16.5 (6-39) months from the clinical onset. At the time of diagnosis, average FVC was 90.4±18.7% of predicted, DLCO 55.4±20.2% and the median GAP index was 3 (2-3). During the median follow-up of 48 months, eight patients (14.8%) had a decline in DLCO of ≥ 15% predicted and/or a decline in FVC of ≥ 10% despite immunosuppressive drugs. Nine patients (17%) died and six of these patients (11.1%) for causes related to ILD.Conclusion:In our study population, the prevalence of ILD as initial manifestation of CTD or RA was 12.6%. Autoimmune myositis, systemic sclerosis and Sjogren syndrome were the most frequent diagnosis. As our data confirmed, ILD is a major cause of death in patients with systemic autoimmune diseases and can progress despite immunosuppression [1]. Furthermore, clinical features may become evident even months after the disease onset. A multidisciplinary evaluation is therefore essential, not only at the time of diagnosis but also during the follow-up [2].References:[1] A. Fischeret al.Progressive fibrosing interstitial lung disease associated with systemic autoimmune diseases.Clin Rheum(2019); 38:2673-81[2] F. Furini,et al. The role of the Multidisciplinary Evaluation of Interstitial Lung Diseases: Systematic Literature Review of the Current Evidence and Future Perspectives.Front Med(2019); 6:246Disclosure of Interests:None declared