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20230905
Open Access Peer-reviewed

Relapsing Polychondritis in a Child with Autism: Rare within Rare 1st Case Described

Aaron Lerner, Jozélio Freire de Carvalho , Thiago Ferreira da Silva, Carina Benzvi, Maria Fernanda Leal dos Santos Ribeiro, Motti Haimi
International Journal of Celiac Disease. 2023, 11(1), 28-31. DOI: 10.12691/ijcd-11-1-6
Received July 27, 2023; Revised August 28, 2023; Accepted September 04, 2023

Abstract

A relationship between autism and autoimmunity is well known and various autoimmune diseases were associated with the autistic spectrum. Relapsing polychondritis is a rare autoimmune disease manifested mainly in adults. Following is the first case presentation of a girl presented with relapsing polychondritis who was on the autistic spectrum. Several mechanisms can be envisioned to connect those two diseases.

1. Introduction

Relapsing polychondritis (RP) is a rare autoimmune disease with a wide individual heterogeneity, involving various human body organs. It is characterized by inflammation of cartilage tissues, mainly in the ears, nose, tracheobronchial tree, but also the inner ear, eyes, joints, cardiovascular system presentations were described 1 2 3 4, Very seldomly central nervous system and psychiatric behavioral manifestations were reported 5 6 7. Despite the fact that autoimmunity, autoantibodies and autism spectrum disorder (ASD) relationship were reported 8, to our knowledge, no ASD were ever described in RP. A subset of patients bears some somatic mutations 9, however, no specific environmental factor was yet discovered 10. Unfortunately, no efficient diagnostic and prognostic molecular biomarkers are available and the current ones lack specificity and sensitivity 11. Clarifying the disease pathophysiology, definitive diagnosis, evaluation of activity, prognosis, and the most efficient therapeutic options remains a challenge 12 13. The present report is unique for the rarity of RP, the early age affected girl and never described association between RP and ASD. Some potential pathophysiological cross talks between RP and ASD will be suggested.

2. Case Presentation

A 7-year-old girl with a history of late neurodevelopment, in February 2020, started polyarthritis of her knees and elbows, episcleritis, associated with redness and pain in her ears (Figure 1). The girl went to the emergency department, and prednisone 0.5mg/kg/day was prescribed, and a marked improvement was observed after four doses of glucocorticoid. Her laboratory tests revealed white blood cells of 12,490, C-reactive protein of 6mg/L, and erythrocyte sedimentation rate (ESR) of 21 mm/1st hour (nr: < 10 mm/1st hour). She came to our consultation, no more arthritis was detected, and the ears and cartilages were normal. We ordered more laboratory tests that showed normal cell blood count, CRP, and ESR. All autoantibodies (antinuclear antibodies, rheumatoid factor, anti-CCP, anti-U1RNP, anti-Ro/SS-A, anti-SS-B, anti-Sm, anti-ribosomal P, anticardiolipin and lupus anticoagulant) were negative. All infectious serologies were negative. Having bilateral auricular scleritis, episcleritis and non-erosive polyarthritis, she fulfilled McAdam/s criteria for the diagnosis of RP 14, hence, hydroxychloroquine 200mg/day and vitamin D 50,000IU/week were then initiated. The child continued to recover, and the glucocorticoid was tapered off. During a 2 year-follow-up, no flare of RP was detected, and all laboratory tests continued within the normal range. In parallel, during the investigation, the parents and the medical team noticed some behavioral changes. She exhibited minimal eye contact, smiled and laughed without reason, had solitary social activities, poor interaction with strangers, and stereotyped gestures. Those characteristics raised the suspicion of autistic spectrum disorder. A thorough neuropsychiatric test's evaluations confirmed the diagnosis of ASD, and the girl was sent for physical, psychologic and phono audiologist therapies and to an appropriate educational framework.

3. Discussion

The present case, to our knowledge, is the first descriptive association between a triple rarity. RP is a rare condition; childhood presentation of RP is rare, where less than 10% of reported patients occur in children and adolescents 15 16 17, and finally, ASD was never reported with this autoimmune entity.

Recent studies suggest immune dysregulation in ASD patients and brain-targeted autoimmune antibodies are increasingly described 8 18 19 20 21. Interestingly, rheumatoid and psoriatic arthritis were related to ASD 22 23, however, the association between RP and ASD was never reported.

An autoimmune background, including brain directed autoantibodies were reported in ASD 8 24 25 26. The autistic spectrum is the fastest-growing neurodevelopmental disability worldwide affecting one in 68 births in the United States, but, the causes and the pathophysiology of ASD are largely yet unknown. genetic abnormalities are increasingly identified but recent emerging studies documented various immune dysfunctions, presenting an additional risk factor for the neurobehavioral deficits observed in ASD 8 18 19 20 21 24 25 26. Taken together, the cross-talks between RP and ASD can involve immune dysbalance or autoimmune phenomena, joininig together in the girl discribed.

Several potential mechanisms can be envisioned to connect the two diseases.

1. Loss of tolerance to a yet unidentified environmental factor.

2. Dysbiosis is a common feature in autoimmune diseases 27 28 29 30 31 and exist in RP. Propionate- producing microbes with suppressed IL-10 induced regulatory T cells was described in RP patients 32. Parallelly, altered composition and decrease variability of the gut microbiome is widely reported in ASD 33 34 35. Intriguingly, co-morbid gastrointestinal symptoms were described in ASD and in joint affected patients 30 31 36 37 38.

3. Increased intestinal permeability is described in ASD 33 and in various rheumatological conditions 39. All the three hypothetical pathways might be a part of the gut-brain axes 31 where luminal and mucosal eco events can irradiate to peripheral organs 38, including all those affected in RP.

4. Conclusions

The present manuscript described the first case of a triple rare conditions. RP is a rare autoimmune inflammatory entity where childhood presentation is rare and its association with ASD was never described. Several mechanisms that might connect RP targeted organs with autism that might bring new therapeutic strategy to both conditions are suggested.

Author's Contribution

AL- screened the literature, wrote the manuscript, JFdC- screened the literature, designed, wrote, edited and revised the manuscript, TFsS- wrote the case presentation, MFLSR, MH, CB-revised and edited the manuscript. The six authors agreed to the published version of the manuscript.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgements

None

Abbreviations

RP-Relapsing polychondritis, ASD-autism spectrum disorder.

References

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In article      View Article  PubMed
 
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In article      View Article  PubMed
 
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In article      View Article
 
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In article      View Article  PubMed
 
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In article      View Article  PubMed
 
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In article      View Article  PubMed
 
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In article      View Article  PubMed
 
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In article      View Article  PubMed
 
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In article      View Article  PubMed
 
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In article      View Article  PubMed
 
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In article      View Article  PubMed
 
[22]  Sun, C.K., Cheng, Y.S., Chen, I.W., Chiu, H.J., Chung, W., Tzang, R.F., Fan, H.Y., Lee, C.W. and Hung, K.C., “Impact of parental rheumatoid arthritis on risk of autism spectrum disorders in offspring: A systematic review and meta-analysis”, Frontiers in Medicine, 9 November 2022.
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In article      View Article
 
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Published with license by Science and Education Publishing, Copyright © 2023 Aaron Lerner, Jozélio Freire de Carvalho, Thiago Ferreira da Silva, Carina Benzvi, Maria Fernanda Leal dos Santos Ribeiro and Motti Haimi

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Cite this article:

Normal Style
Aaron Lerner, Jozélio Freire de Carvalho, Thiago Ferreira da Silva, Carina Benzvi, Maria Fernanda Leal dos Santos Ribeiro, Motti Haimi. Relapsing Polychondritis in a Child with Autism: Rare within Rare 1st Case Described. International Journal of Celiac Disease. Vol. 11, No. 1, 2023, pp 28-31. http://pubs.sciepub.com/ijcd/11/1/6
MLA Style
Lerner, Aaron, et al. "Relapsing Polychondritis in a Child with Autism: Rare within Rare 1st Case Described." International Journal of Celiac Disease 11.1 (2023): 28-31.
APA Style
Lerner, A. , Carvalho, J. F. D. , Silva, T. F. D. , Benzvi, C. , Ribeiro, M. F. L. D. S. , & Haimi, M. (2023). Relapsing Polychondritis in a Child with Autism: Rare within Rare 1st Case Described. International Journal of Celiac Disease, 11(1), 28-31.
Chicago Style
Lerner, Aaron, Jozélio Freire de Carvalho, Thiago Ferreira da Silva, Carina Benzvi, Maria Fernanda Leal dos Santos Ribeiro, and Motti Haimi. "Relapsing Polychondritis in a Child with Autism: Rare within Rare 1st Case Described." International Journal of Celiac Disease 11, no. 1 (2023): 28-31.
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[1]  Grygiel-Górniak, B., Tariq, H., Mitchell, J., Mohammed, A. and Samborski, W., “Relapsing polychondritis: state-of-the-art review with three case presentations”, Postgraduate medicine, 133 (8). 953-963. 2021.
In article      View Article  PubMed
 
[2]  Rednic, S., Damian, L., Talarico, R., Scirè, C.A., Tobias, A., Costedoat-Chalumeau, N., Launay, D., Mathian, A., Mattews, L., Ponte, C., et al., “Relapsing polychondritis: state of the art on clinical practice guidelines”, RMD open, 4 (Suppl 1). October 2018.
In article      View Article  PubMed
 
[3]  Borgia, F., Giuffrida, F., Guarneri, F. and Cannavò, S.P., “Relapsing Polychondritis: An Updated Review”, Biomedicines, 6 (3). September 2018.
In article      View Article  PubMed
 
[4]  Schumacher, S. and Pieringer, H., “Relapsing polychondritis: a chameleon among orphan diseases”, Wiener medizinische Wochenschrift (1946), 167 (9-10). 227-233. June 2017.
In article      View Article  PubMed
 
[5]  Lokken, A. and Wang, A., “Relapsing Polychondritis as a Cause of Sudden and Unexpected Death With Central Nervous System Involvement”, The American journal of forensic medicine and pathology, 43 (3). 263-268. September 2022.
In article      View Article  PubMed
 
[6]  Chernyak, V.I., Savel’ev A I, Men’shikova, I. V. and Pogromov, A.P., “NERVOUS SYSTEM LESIONS ASSOCIATED WITH RELAPSING POLYCHONDRITIS: ANALYSIS OF ORIGINAL OBSERVATIONS”, Klinicheskaia meditsina, 94 (2). 108-113. 2016.
In article      View Article
 
[7]  Liu, L., Liu, S., Guan, W. and Zhang, L., “Efficacy of tocilizumab for psychiatric symptoms associated with relapsing polychondritis: the first case report and review of the literature”, Rheumatology international, 36 (8). 1185-1189. August 2016.
In article      View Article  PubMed
 
[8]  Edmiston, E., Ashwood, P. and Van de Water, J., “Autoimmunity, Autoantibodies, and Autism Spectrum Disorder”, Biological psychiatry, 81 (5). 383-390. March 2017.
In article      View Article  PubMed
 
[9]  Ferrada, M.A., Sikora, K.A., Luo, Y., Wells, K. V., Patel, B., Groarke, E.M., Ospina Cardona, D., Rominger, E., Hoffmann, P., Le, M.T., et al., “Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS”, Arthritis & rheumatology (Hoboken, N.J.), 73 (10). 1886-1895. October 2021.
In article      View Article  PubMed
 
[10]  Yoshida, T., Yoshifuji, H., Shirakashi, M., Nakakura, A., Murakami, K., Kitagori, K., Akizuki, S., Nakashima, R., Ohmura, K. and Morinobu, A., “Risk factors for the recurrence of relapsing polychondritis”, Arthritis research & therapy, 24 (1). December 2022.
In article      View Article  PubMed
 
[11]  Liu, Y., Li, X., Cheng, L., Zhan, H., Huang, Y., Li, H. and Li, Y., “Progress and Challenges in the Use of Blood Biomarkers in Relapsing Polychondritis”, Clinical and experimental immunology, February 2023.
In article      View Article  PubMed
 
[12]  Petitdemange, A., Sztejkowski, C., Damian, L., Martin, T., Mouthon, L., Amoura, Z., Cutolo, M., Burmester, G.R., Fonseca, J.E., Rednic, S., et al., “Treatment of relapsing polychondritis: a systematic review”, Clinical and experimental rheumatology, 40 Suppl 134 (5). S81-S85. May 2022.
In article      View Article  PubMed
 
[13]  Kemta Lekpa, F. and Chevalier, X., “Refractory relapsing polychondritis: challenges and solutions”, Open access rheumatology: research and reviews, 10 1-11. January 2018.
In article      View Article  PubMed
 
[14]  McAdam, L.P., O’Hanlan, M.A., Bluestone, R. and Pearson, C.M., “Relapsing polychondritis: Prospective study of 23 patients and a review of the literature”, Medicine (United States), 55 (3). 193-215. 1976.
In article      View Article  PubMed
 
[15]  Alqanatish, J.T., Alfarhan, B.A. and Qubaiban, S.M., “Limited auricular relapsing polychondritis in a child treated successfully with infliximab”, BMJ Case Reports, 12 (5). May 2019.
In article      View Article  PubMed
 
[16]  Alqanatish, J.T. and Alshanwani, J.R., “Relapsing polychondritis in children: A review”, Modern Rheumatology, 30 (5). 788-798. September 2020.
In article      View Article  PubMed
 
[17]  Fonseca, A.R., De Oliveira, S.K.F., Rodrigues, M.C.F., Aymoré, I.L., Domingues, R.C. and Sztajnbok, F.R., “Relapsing polychondritis in childhood: Three case reports, comparison with adulthood disease and literature review”, Rheumatology International, 33 (7). 1873-1878. July 2013.
In article      View Article  PubMed
 
[18]  Erbescu, A., Papuc, S.M., Budisteanu, M., Arghir, A. and Neagu, M., “Re-emerging concepts of immune dysregulation in autism spectrum disorders.”, Frontiers in psychiatry, 13 1006612. October 2022.
In article      View Article  PubMed
 
[19]  Hughes, H.K., R.J.Moreno and Ashwood, P., “Innate immune dysfunction and neuroinflammation in autism spectrum disorder (ASD)”, Brain, Behavior, and Immunity, 108 245-254. February 2023.
In article      View Article  PubMed
 
[20]  Simone, M., De Giacomo, A., Palumbi, R., Palazzo, C., Lucisano, G., Pompamea, F., Micella, S., Pascali, M., Gabellone, A., Marzulli, L., et al., “Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Potential Diagnostic Biomarkers in Autism Spectrum Disorders: A Preliminary Study”, International Journal of Molecular Sciences, 24 (3). February 2023.
In article      View Article  PubMed
 
[21]  Nour-Eldine, W., Ltaief, S.M., Abdul Manaph, N.P. and Al-Shammari, A.R., “In search of immune cellular sources of abnormal cytokines in the blood in autism spectrum disorder: A systematic review of case-control studies”, Frontiers in Immunology, 13 October 2022.
In article      View Article  PubMed
 
[22]  Sun, C.K., Cheng, Y.S., Chen, I.W., Chiu, H.J., Chung, W., Tzang, R.F., Fan, H.Y., Lee, C.W. and Hung, K.C., “Impact of parental rheumatoid arthritis on risk of autism spectrum disorders in offspring: A systematic review and meta-analysis”, Frontiers in Medicine, 9 November 2022.
In article      View Article  PubMed
 
[23]  Bernardini, N., Skroza, N., Marraffa, F., Prevete, E., Mambrin, A., Proietti, I., Tolino, E., Caviglia, M., Di Guardo, A., Rossi, G., et al., “A case of twins affected by psoriasis, psoriatic arthritis and autism: Five years of efficacious and safe treatment with Secukinumab”, Dermatologic Therapy, 35 (7). July 2022.
In article      View Article
 
[24]  Heidari, A., Rostam-Abadi, Y. and Rezaei, N., “The immune system and autism spectrum disorder: association and therapeutic challenges”, Acta neurobiologiae experimentalis, 81 (3). 249-263. 2021.
In article      View Article  PubMed
 
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