Sjogren’s, systemic lupus and relapsing polychondritis. A diverse array of autoimmune diseases in one patient. Case report and review of literature

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Case Report

Sjogren’s, systemic lupus and relapsing polychondritis. A diverse array of autoimmune diseases in one patient. Case report and review of literature

https://doi.org/10.21203/rs.3.rs-2506332/v1

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Relapsing polychondritis (RPC) is a rare inflammatory disorder that affects the cartilaginous structures with variable clinical and laboratory manifestations. Although it is commonly associated with other diseases, it has been only rarely reported to be associated with either systemic lupus erythematosus (SLE) or Sjogren syndrome (SS). In this report, we describe the case of a middle-aged lady who presented with right ear pain, redness, swelling and tenderness along with high inflammatory markers. She was found to have symptoms of dry mouth and dry eyes along with arthritis, rash and photosensitivity. Serological workup revealed the positivity of ANA, anti-RO, U1-RNP, and anti-smith antibodies. With these clinical and serological results, she was diagnosed with RPC and with both SLE and SS, an overlap we believe was never reported before. In conclusion, RPC can be associated with other rheumatological diseases and rarely with more than a disease in one patient. Careful assessment is needed to diagnose and treat such patients.

Relapsing polychondritis

Systemic lupus erythematosus

Sjogren’s syndrome

case report

Relapsing polychondritis (RPC) is a rare inflammatory disorder first described in 1923 (1). The disease is characterized by inflammation of the cartilaginous structures in an episodic manner across different areas of the body including ears, nose, and tracheobronchial tree among others (2), (3). Because of the disease's rarity, it is difficult to establish the exact disease prevalence. However, the incidence is estimated to be somewhere between 3.4 and 4.5 cases per million yearly (4).

The clinical manifestations of the disease as well as the course vary notably between patients without solid clinical or laboratory measures that predict the overall disease course. Subtle, early features are often missed for prolonged periods leading to a significant delay in establishing the diagnosis and starting appropriate treatment (5). RPC exists with other diseases in almost a third of patients. In most cases, with other autoimmune connective tissue diseases particularly systemic vasculitis. On other occasions, the disease co-exists in patients with malignancies like myelodysplastic syndrome (MDS) who usually have more pronounced cutaneous manifestations (2),(6).

Few reports described the coexistence of the disease with systemic lupus erythematosus (SLE) or Sjogren’s syndrome (SS). Herein, we report the first case with an overlap of RPC, SLE and SS in the same patient. We as well described the few available cases in the literature describing the occurrence of RPC with SLE or SS.

A 47-year-old female patient presented to the emergency department complaining of right ear pain, redness and swelling of a 3-day-duration. The pain started mild and increased gradually till it became intolerable on the day of admission. There was no history of trauma, ear discharge, hearing loss, dizziness, cough, dyspnea, changing of voice or fever. On examination, Temperature 36.5°C, saturation 98%, pulse 80 beats per minute, blood pressure 119/66 mmHg. The right auricle was red, swollen and very tender. The inflammation was confined to the ear cartilaginous part sparing the lobule (Figure.1). The nose was normal in shape, with normal mucosa and the septum was intact. The oral cavity showed dry mucosa and fissured tongue. No visual field defects, ptosis, proptosis or lid problems were found. Auscultation of the chest showed normal breath sound, no wheezing, strider or any added sound. The cardiovascular was normal with no murmurs detected. The exam was otherwise unremarkable. The initial laboratory results showed the following: normal complete blood count (CBC), kidney functions, liver function tests, and urine analysis. Erythrocytes sedimentation rate (ESR) was 55mm/hr and C-reactive protein (CRP) was 57mg/L. At first, the patient was suspected to have an infection and was started on ceftriaxone 2 grams daily which was switched to levofloxacin 750mg PO daily because of inefficacy. On day 10 of admission, because of the persistence of pain and swelling, rheumatology was consulted. Upon further evaluation of the patient history, she admitted to having a similar episode 4 years back on the contralateral side for which she was admitted to another hospital and received IV medications for 2 weeks. That episode lasted for 8 weeks. She was also found to have chronic ocular and mouth dryness for 2 years. The patient reported as well having recurrent attacks of joint pain and swelling involving the wrists and elbows lasting for 3–5 days every 3–6 weeks for which she was receiving over-the-counter NSAID. The attacks ended after a few days with complete resolution. She also described a chronic history of hand pain with morning stiffness of 30 minutes duration. She has photosensitivity manifesting as erythematous skin patches upon exposure to the sunlight lasting for 1–2 days but has no persistent malar rash. She denied any history suggestive of Raynaud’s, mouth ulcers, genital ulcers, significant hair loss, weight loss, parotid swelling, hearing loss, or pleuritic chest pain. She has no family history of rheumatological diseases, psoriasis or inflammatory bowel disease.

SLE overlap with SS was suspected so further evaluation with blood tests was sought. Her serology was positive for antinuclear antibodies (ANA). The extractable nuclear antigens (ENA) panel was positive for anti-RO, U1-RNP, AMA M2 and anti-smith antibodies. The serology for anti-ds-DNA and antineutrophil cytoplasmic antibodies was negative. Complements levels were normal. Chest x-ray and pulmonary functions tests were normal as well.

At first, she was started on hydroxychloroquine (HCQ) 200mg PO BID and an anti-inflammatory dose of ibuprofen 800mgPO TID which was changed later to Celecoxib 200mg PO BID because of inefficacy. The patient only had minimal response to NSAIDs she so was started on prednisolone 30mg PO daily in addition to celecoxib and HCQ. A few days after steroids she started to have significant improvement and was discharged. After 10 days of steroids, she had complete resolution of the ear disease and the prednisolone was tapered to 5mg at the end of 3 weeks. After one week of steroids tapering, she presented to the clinic with left elbow synovitis manifested with significant tenderness and swelling associated with redness. The synovitis continued for more than one week despite the use of NSAIDS and low-dose steroids so prednisolone was increased to 15mg PO daily and Methotrexate (MTX) 15 mg once weekly was started together with folic acid 5mg once weekly, while continuing the HCQ 400 mg daily. The joint and auricular disease improves completely and she was followed in the clinic with a plan of slow steroids tapering. Her sicca symptoms were managed with topical ocular refreshing eye drops and lubricant as well as saliva substitutes. Over the duration of 7 months of follow-up, steroids were tapered to prednisolone 2.5mg PO daily. She continued to take methotrexate and HCQ at the same dose. Her disease was controlled with no recurrence of the joint, skin or auricular disease. Her last blood tests showed normal CBC, kidney functions, liver function tests, and urine analysis with much improved inflammatory markers; ESR: 30mm/hr and CRP: 4.9 mg/L.

The patient was diagnosed with RPC based on Modified Damiani criteria (7). Based on the clinical manifestations and blood tests, our patient is diagnosed with SLE and met the 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus (8). The diagnosis of SS was based on persistent mouth and ocular dryness and was supported by the positive SS-A/ Ro. The progression of the disease was controlled by MTX and HCQ along with a tapering steroid regimen. Similar to our case, auricular disease in RPC is often associated with remarkable pain and tenderness (9). It is usually the initial presentation and might be initially misdiagnosed as an infection, particularly at the start of the disease (9).

The cartilage inflammation in RPC is associated with an acute phase characterized by neutrophilic infiltration into the cartilaginous matrix, lacunar breakdown, acidophilia and the disappearance of basophilia and metachromasia. This is followed by a chronic phase characterized by infiltration with plasma cells, lymphocytes and fibroblasts which eventually leads to fibrosis (10).

We searched the literature from 1980 to the current date for RPC cases overlapping with SLE or SS and the search revealed very limited case reports (11, 12, 13, 14, 15, 16, 17, 18, 19, 20) and were described in Tables 1 and 2, respectively. Reports of RPC having a sex predilection are controversial; many reports suggested that men and women are affected equally in RPC. However, other reports suggest a slight female predominance of the disease, in a ratio of 3:1 (2). In contrast, we found that all RPC in patients with SLE (RPC-SLE) and RPC in patients with SS (RPC-SS) were females, which is more consistent with the sex distribution of SLE and SS in females in general. The mean age of patients with RPC-SLE and RPC-SS was 38.6 years and 38.7 years, respectively. This is younger than RPC in general where the average age of onset is estimated to be around 51 years and 55 years in men and women respectively (21), while most cases start between 40 and 60 years (2), (22).

Table 1

Summary of the major characteristics of Relapsing polychondritis patients with Sjogren’s syndrome.
Case (Year)	Age at diagnosis of RPC (years)	Sex	Country/ Ethnicity	Chronological order	Serology (RF, ANA, ENA, anti-CCP, ANCA).	Site of chondritis	CTD manifestations	Treatment	Outcome and follow up
Centala (2021) (13)	56	Female	Asian	Started after undefined duration of xerostomia and xerophthalmia	- ANA + ve - RF + ve - Anti-Ro/SSA: +ve - Anti-La/SSB: +ve - ANCA-ve	Auricle (Presenting feature)	- Preauricular rashes and cartilaginous edema - Arthralgia of bilateral shoulders, wrists, and knees - Mild xerostomia and xerophthalmia	- 2.5% hydrocortisone (topical) - Hydroxychloroquine 200 mg daily - Ibuprofen twice daily	Two attacks over 4 months. Complete resolution with no sequelae. (4 months of follow up)
Tajiri (2019) (14)	26	Female	Ascian/Japan	Not mentioned	- Serology is not mentioned.	- Auricle	- Arthritis - Skin involvement	- Prednisolone 15 mg	Not mentioned
Harada (1995) (15)	25	Female	Asian	After 5 years of SS diagnosis	- (ANA) + ve - Anti-Ro/SSA + ve - Anti-La/SSB -ve - RF -ve - Anti-human cartilage antibody + ve	- Auricle bilateral - Nasal bridge cartilage	- Fever - Arthritis - Seronegative inflammatory arthritis	- Antibiotics (flomoxef sodium, clindamycin phosphate) - (Ioxoprofen)	Complete resolution (Follow up duration is not mentioned)
Rodriguez (1989) (16)	48	Female	(Not mentioned)	- After 20 years of Sjogren’s syndrome - And after 3 years of diagnosis of rapidly progressive glomerulonephritis (RPGN)	- ANA + ve - Anti-Ro/SSA + ve - RF + ve	Both Auricles	- Xerostomia - Xerophthalmia - RPGN	prednisone to 30 mg daily followed with 2–5 mg daily.	Complete resolution With no recurrence of the disease after one year of follow up
RPC = Relapsing polychondritis; NSAIDs: Non-steroidal anti-inflammatory drugs; CTD = connective tissue disease; RF = rheumatoid factor; EN = Extractable nuclear antigens; ANA = Anti-nuclear antibodies; ANCA = antineutrophil cytoplasmic antibodies; ds-DNA = double-stranded deoxyribonucleic acid; CCP: cyclic citrullinated peptide; +ve = Positive; -ve = Negative.

Table 2

Summary of the major characteristics of Relapsing polychondritis patients with systemic lupus erythematosus syndrome
Case/year	Age at diagnosis of RPC (years)	Sex	Country/ Ethnicity	Chronological order	Serology (RF, ANA, ENA, anti-CCP, ANCA)	Site of chondritis	CTD manifestations	Treatment	Outcome and follow up
Nguyen (2016) (17)	47	Female	Not mentioned	Not mentioned	- ANA 1:640 - Anti-smith antibody + ve - RF + ve - Anti-Ro/SSA + ve - Anti-U1-RNP + Ve	- Auricle (bilateral)	- Fever, malaise, and weight loss. - Oral ulcers - Photosensitivity - Discoid lupus eruption - Lupus nephritis (class II) - Polyarthritis - Xerostomia	- Prednisone - Hydroxychloroquine.	Not mentioned
Lenormand 2008 (18)	31	Male	Caucasian	After 5-years of the cutaneous manifestations.	- ANA (1:1280) - Anti-Ro/SSA + ve - Anti-La/SSB + ve-	- Auricle	- Red papules and plaques of the forehead, cheeks, and neck - Photosensitivity - Arthritis - Neutropenia and low complement.	- Photoprotection - Hydroxychloroquine - NSAIDS ( - Dapsone (100 mg daily)	Six-year follow-up complete recovery with no recurrence or sequelae.
Roux (2004) (19)	59	Female	Not mentioned	Not mentioned	- ANA + ve	- Nasal septum	- Suspected lupus. - Arthritis. - Hemolytic anemia. - Antiphospholipid syndrome (stroke) and livedo reticularis.	Corticosteroid therapy at 1 mg/kg per day is started	Saddle nose
Harisdangkul (1994) (20)	38	Female	South America	Not mentioned	- ANA 1:800 - Anti-dsDNA + VE	Both auricles (Recurrent attacks)	- Arthritis (shoulders, elbows, wrists, hips, knees, and PIPs) - Episcleritis	Prednisone 20mg	Complete resolution. No follow up
Bellon (2013) (21)	32	Female	Not mentioned	Not mentioned	- AN 1:1280 - anti-DNA antibodies + ve. - Anti-Ro/SSA + ve. - Anti-La/SSB + ve. - Anti-ADAMTS-13 + ve	Auricle Nose	- asthenia. - Thrombotic microangiopathy: low ADAMTS-13activity, anemia, multiple small brain infarcts, mild kidney failure) - low complements.	- Prednisone (1 mg/kg/day). - Hydroxychloroquine (400 mg/day), - Plasma exchange - Rituximab (three doses of 375 mg/m2)	Not mentioned
Small (1980) (22) Case-1	34	Female	Caucasian	After cutaneous manifestations	- ANA + ve	Auricle	- Photosensitivity. - Arthralgias. - Discoid lupus.	Not mentioned	Not mentioned
Small (1980) (22) Case-2	29	Female	Caucasian	After a 9-year history of SLE.	- ANA + ve. - Anti-ds-DNA + ve.	Auricle	- Arthritis - Photosensitivity. - Lupus nephritis	- Prednisone 10 mg daily for 5 days	Not mentioned
RPC = Relapsing polychondritis; NSAIDs: Non-steroidal anti-inflammatory drugs; CTD = connective tissue disease; RF = rheumatoid factor; EN = Extractable nuclear antigens; ANA = Anti-nuclear antibodies; ANCA = antineutrophil cytoplasmic antibodies; ds-DNA = double-stranded deoxyribonucleic acid; CCP: cyclic citrullinated peptide; +ve = Positive; -ve = Negative.

All patients with RPC-SLE and RPC-SS had auricular inflammation. Like RPC in general in which auricular disease affects nearly 90% of patients. Forty percent of patients with RPC present with the auricular disease either unilateral or bilateral (23). Most patients (78%) with RPC-SS and RPC-SLE had arthralgia/arthritis similar to RPC in general (80 percent) which is usually of small joints (4). The severity of the disease was mild and resulted in no sequela in most of the patients. The morbidity of the disease was mainly associated with SLE and SS, not due to RPC. Treatment of RPC-SLE and RPC-SS varied from non-steroidal anti-inflammatory drugs (NSAIDs), topical steroids, and steroids sparing agents such as hydroxychloroquine and dapsone. One patient received rituximab and plasmapheresis but this was targeted more to other SLE and SS manifestations (20).

RPC is a rare disease that may complicate autoimmune CTDs such as SLE and SS. In such patients, the disease is usually benign with no chronic sequela. The majority of patients with RPC-SS and RPC-SLE are middle-aged females. Physicians and rheumatologists should be aware of this coexistence as it might be the presenting complaint. Herein we report a rare coexistence of CTD with SLE and SS in the same patient who was treated successfully with a tapering dose of steroids, NSAIDs, MTX, and HCQ.

Competing interests

The authors declare that they have no competing interests.

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Ethics approval and consent to participate

Ethical approval not required, as this is a case report.

The patient gave consent for her case to be published in this case report.

Consent for publication

Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Availability of data and materials

All data generated or analysed during this study are included in this published article.

Funding

No funding was received to carry out the work described in this manuscript.

Author contribution

Study concept or design: Laith Alamlih.

Writing the manuscript: Layth Al-Karaja, Jafar Matar, Mutaz Albakri, Eshraq Shalalfa.

Review & editing the manuscript: All authors reviewed the manuscript

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Sjogren’s, systemic lupus and relapsing polychondritis. A diverse array of autoimmune diseases in one patient. Case report and review of literature

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