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Relapsing polychondritis
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<h2 id="signs-and-symptoms">Signs and symptoms</h2> <p>Though any cartilage in the body may be affected in persons with relapsing polychondritis, in many cases the disease affects several areas while sparing others. The disease may be variable in its signs and symptoms, resulting in a difficult diagnosis which may leads to delayed recognition for several months, years or decades.<a class="footnote-ref" id="fnref:1" href="#fn:1"><sup>1</sup></a> </p> <h3>Associated diseases</h3> <p>There are several other overlapping diseases associated with RP, that should also be taken into account. About one-third of people with RP might be associated with other autoimmune diseases, vasculitides and hematologic disorders.<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a> Systemic vasculitis is the most common association with RP, followed by rheumatoid arthritis and systemic lupus erythematosus.<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> The following table displays the main diseases in association with RP. </p> <table><tbody><tr><th>Class of disease</th><th>Specific type of disease</th></tr><tr><td>Vasculitides</td><td><a href="/facts/Granulomatosis_with_polyangiitis/TPu4mHpD">Granulomatosis with polyangiitis</a>,<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> <a href="/facts/Eosinophilic_granulomatosis_with_polyangiitis/3FDUbbpT">eosinophilic granulomatosis with polyangiitis</a>,<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> <a href="/facts/Polyarteritis_nodosa/RbFBUVKG">polyarteritis nodosa</a>,<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> <a href="/facts/Beh%25C3%25A7et%2527s_disease/oah5LIcL">Behçet's disease</a>,<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a><a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> <a href="/facts/Takayasu%2527s_arteritis/tM6FJSpd">Takayasu's arteritis</a>,<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> <a href="/facts/Leukocytoclastic_vasculitis/HujlWxwL">leukocytoclastic vasculitis</a>,<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> <a href="/facts/Temporal_arteritis/3X1GdNRR">temporal arteritis</a><a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> and <a href="/facts/Systemic_vasculitis/AkVcSu2X">systemic vasculitis</a>.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a></td></tr><tr><td>Autoimmune diseases</td><td><a href="/facts/Systemic_lupus_erythematosus/kfHYawre">Systemic lupus erythematosus</a>,<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> <a href="/facts/Systemic_scleroderma/K4UQIlxk">systemic scleroderma</a>,<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> <a href="/facts/Mixed_connective_tissue_disease/3NgWCz7h">mixed connective tissue disease</a>,<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a><a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> <a href="/facts/Autoimmune_thyroiditis/RT7gSMxp">autoimmune thyroiditis</a>,<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> <a href="/facts/Sj%25C3%25B6gren%2527s_syndrome/U1p9IbFU">Sjögren's syndrome</a>,<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> <a href="/facts/Dermatomyositis/VDJk2fE5">dermatomyositis</a>,<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> <a href="/facts/Antiphospholipid_syndrome/8R4fk5FP">antiphospholipid syndrome</a>,<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> <a href="/facts/Autoimmune_hemolytic_anemia/cQeKSWIK">autoimmune hemolytic anemia</a>,<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> <a href="/facts/Hashimoto%2527s_thyroiditis/myBntJv5">Hashimoto's thyroiditis</a>.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a></td></tr><tr><td>Other Rheumatologic diseases</td><td><a href="/facts/Rheumatoid_arthritis/qFK4Xwv7">Rheumatoid arthritis</a>,<a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a><a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a> <a href="/facts/Spondyloarthropathy/X5m92l1X">spondyloarthropathy</a>,<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a><a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> <a href="/facts/Reactive_arthritis/rW1jrRd1">reactive arthritis</a>,<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a> <a href="/facts/Polymyalgia_rheumatica/xppFrdDH">polymyalgia rheumatica</a>.<a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a><a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a></td></tr><tr><td>Hematologic disorders</td><td><a href="/facts/Myelodysplasia/6ppeUYWk">Myelodysplasia</a>,<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a> <a href="/facts/Myeloproliferative_neoplasm/Wt1JuLC6">myeloproliferative neoplasm</a>.<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a><a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a></td></tr><tr><td>Dermatologic diseases</td><td><a href="/facts/Psoriasis/WW1k1LsH">Psoriasis</a>,<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a> <a href="/facts/Atopic_dermatitis/DvmdVwWu">atopic dermatitis</a>,<a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> <a href="/facts/Lichen_ruber_planus/R82WnXep">lichen ruber planus</a>,<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> <a href="/facts/Vitiligo/d8xPRXQB">vitiligo</a>.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a></td></tr><tr><td>Autoinflammatory diseases</td><td><a href="/facts/Familial_Mediterranean_fever/fRRPvWdE">Familial Mediterranean fever</a>.<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a></td></tr><tr><td>Others</td><td><a href="/facts/Primary_biliary_cirrhosis/9X0f10mz">Primary biliary cirrhosis</a>,<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a><a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a> <a href="/facts/Ulcerative_colitis/BIkyFzRj">ulcerative colitis</a>,<a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a> <a href="/facts/Crohn%2527s_disease/zm55cBtd">Crohn's disease</a>,<a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a> <a href="/facts/Diabetes_mellitus/2xeHXbsI">diabetes mellitus</a>,<a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a> <a href="/facts/Pulmonary_fibrosis/9RVcVylE">pulmonary fibrosis</a>.<a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a></td></tr></tbody></table> <h3>Cartilage inflammation</h3> <p><a href="/facts/Chondritis/7LUHnHPy">Cartilage inflammation</a> (technically known as chondritis) that is relapsing is very characteristic of the disease.<a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a> These recurrent episodes of inflammation over the course of the disease may result in <a href="/facts/Degeneration_(medicine)/j174EjWc">breakdown</a> and <a href="/facts/Atrophy/QNxSoxDV">loss</a> of cartilage.<a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a> The signs and symptoms of cartilage inflammation in various parts of the body will be described first. </p> <h4>Ear</h4> <p>Inflammation of the cartilage of the <a href="/facts/Ear/UayK1RIP">ear</a> is a specific symptom of the disease and affects most people.<a class="footnote-ref" id="fnref:47" href="#fn:47"><sup>47</sup></a> It is present in about 20% of persons with RP at presentation and in 90% at some point.<a class="footnote-ref" id="fnref:48" href="#fn:48"><sup>48</sup></a> Both ears are often affected but the inflammation may alternate between either ear during a relapse.<a class="footnote-ref" id="fnref:49" href="#fn:49"><sup>49</sup></a> It is characteristic for the entire <a href="/facts/Pinna_(anatomy)/J2RDSQJy">outer part of the ear</a> except the earlobe to be swollen, red, or less often purplish, warm and painful to light touch.<a class="footnote-ref" id="fnref:50" href="#fn:50"><sup>50</sup></a> </p><p>The inflammation of the ear usually lasts a few days or more, rarely a few weeks, and then resolves spontaneously and recurs at various intervals.<a class="footnote-ref" id="fnref:51" href="#fn:51"><sup>51</sup></a> Because of the loss of cartilage, after several flares <a href="/facts/Cauliflower_ear/lDE7Net1">cauliflower ear</a> deformity may result.<a class="footnote-ref" id="fnref:52" href="#fn:52"><sup>52</sup></a> The outer part of the ear may be either floppy or hardened by calcifications of the <a href="/facts/Scar/XSQ92JoG">scar tissue</a> that replaces the cartilage.<a class="footnote-ref" id="fnref:53" href="#fn:53"><sup>53</sup></a> These cauliflower ear deformities occur in about 10% of persons with RP.<a class="footnote-ref" id="fnref:54" href="#fn:54"><sup>54</sup></a> </p> <h4>Nose</h4> <p>The inflammation of the cartilage of the <a href="/facts/Nose/Kv0lv34S">nose</a> involves the bridge of the nose and is often less marked than the ears.<a class="footnote-ref" id="fnref:55" href="#fn:55"><sup>55</sup></a> Statistics show that this clinical manifestation is present in 15% of persons with RP and occurs at some point in 65% of persons with RP.<a class="footnote-ref" id="fnref:56" href="#fn:56"><sup>56</sup></a> <a href="/facts/Nasal_obstruction/xClWzxrg">Nasal obstruction</a> is not a common feature.<a class="footnote-ref" id="fnref:57" href="#fn:57"><sup>57</sup></a> <a href="/facts/Atrophy/QNxSoxDV">Atrophy</a> may eventually develop secondarily during the disease, this appears gradual and is not easily noticed.<a class="footnote-ref" id="fnref:58" href="#fn:58"><sup>58</sup></a> This can result in collapse of the nasal septum with saddle-nose deformity, which is painless but irreversible.<a class="footnote-ref" id="fnref:59" href="#fn:59"><sup>59</sup></a> </p> <h4>Respiratory tract</h4> <p>Inflammation occurs in the laryngeal, tracheal and bronchial cartilages.<a class="footnote-ref" id="fnref:60" href="#fn:60"><sup>60</sup></a> Both of these sites are involved in 10% of persons with RP at presentation and 50% over the course of this autoimmune disease, and is more common among females.<a class="footnote-ref" id="fnref:61" href="#fn:61"><sup>61</sup></a> The involvement of the laryngotracheobronchial cartilages may be severe and life-threatening; it causes one-third of all deaths among persons with RP.<a class="footnote-ref" id="fnref:62" href="#fn:62"><sup>62</sup></a><a class="footnote-ref" id="fnref:63" href="#fn:63"><sup>63</sup></a> Laryngeal chondritis is manifested as pain above the <a href="/facts/Thyroid/bjovTJVu">thyroid</a> gland and, more importantly, as <a href="/facts/Dysphonia/IMSjzPrP">dysphonia</a> with a hoarse voice or transient <a href="/facts/Aphonia/6fcTxDWw">aphonia</a>.<a class="footnote-ref" id="fnref:64" href="#fn:64"><sup>64</sup></a> Because this disease is relapsing, recurrent laryngeal inflammation may result in <a href="/facts/Laryngomalacia/o1WjdFcp">laryngomalacia</a> or permanent laryngeal <a href="/facts/Stenosis/X0x2tAk7">stenosis</a> with inspiratory <a href="/facts/Dyspnea/1jBfFzxU">dyspnea</a> that may require emergency <a href="/facts/Tracheotomy/wV3NCaly">tracheotomy</a> as a temporary or permanent measure.<a class="footnote-ref" id="fnref:65" href="#fn:65"><sup>65</sup></a> </p><p>Tracheobronchial involvement may or may not be accompanied with laryngeal chondritis and is potentially the most severe manifestation of RP. </p><p>The symptoms consist of dyspnea, wheezing, a nonproductive cough.<a class="footnote-ref" id="fnref:66" href="#fn:66"><sup>66</sup></a><a class="footnote-ref" id="fnref:67" href="#fn:67"><sup>67</sup></a> Obstructive respiratory failure may develop as the result of either permanent tracheal or bronchial narrowing or <a href="/facts/Chondromalacia/f49E497e">chondromalacia</a> with expiratory collapse of the tracheobronchial tree.<a class="footnote-ref" id="fnref:68" href="#fn:68"><sup>68</sup></a> Endoscopy, intubation, or tracheotomy has been shown to hasten death.<a class="footnote-ref" id="fnref:69" href="#fn:69"><sup>69</sup></a> </p> <h4>Ribs</h4> <p>Involvement of the rib cartilages results in <a href="/facts/Costochondritis/0wxSKvuu">costochondritis</a>.<a class="footnote-ref" id="fnref:70" href="#fn:70"><sup>70</sup></a> Symptoms include chest wall pain or, less often, swelling of the involved cartilage.<a class="footnote-ref" id="fnref:71" href="#fn:71"><sup>71</sup></a> The involvement of the ribs is seen in 35% of persons with RP but is rarely the first symptom.<a class="footnote-ref" id="fnref:72" href="#fn:72"><sup>72</sup></a> </p> <h3>Other manifestations</h3> <p>Relapsing polychondritis may affect many different organ systems of the body. At first, some people with the disease may have only nonspecific symptoms such as fever, weight loss, and malaise.<a class="footnote-ref" id="fnref:73" href="#fn:73"><sup>73</sup></a> </p> <h4>Joint</h4> <p>The second most common clinical finding of this disease is joint pain with or without arthritis, after chondritis.<a class="footnote-ref" id="fnref:74" href="#fn:74"><sup>74</sup></a><a class="footnote-ref" id="fnref:75" href="#fn:75"><sup>75</sup></a> All synovial joints may be affected.<a class="footnote-ref" id="fnref:76" href="#fn:76"><sup>76</sup></a><a class="footnote-ref" id="fnref:77" href="#fn:77"><sup>77</sup></a> </p><p>At presentation, around 33% of people have joint symptoms that involve Polyarthralgia and/or polyarthritis or oligoarthritis that affects various parts of the body and often appears to be episodic, asymmetric, migratory and non-deforming.<a class="footnote-ref" id="fnref:78" href="#fn:78"><sup>78</sup></a> The most common sites of involvement are the metacarpophalangeal joints, proximal interphalangeal joints and knees. After which is followed by the ankles, wrists, metatarsophalangeal joints and the elbows.<a class="footnote-ref" id="fnref:79" href="#fn:79"><sup>79</sup></a> Any involvement of the axial skeleton is considered to be very rare.<a class="footnote-ref" id="fnref:80" href="#fn:80"><sup>80</sup></a> Tests for rheumatoid factor are negative in affected persons with RP, unless there is a co-morbidity with RA.<a class="footnote-ref" id="fnref:81" href="#fn:81"><sup>81</sup></a> </p><p>Less often it has been reported that persons may experience arthralgia, monoarthritis, or chronic polyarthritis that mimics <a href="/facts/Rheumatoid_arthritis/qFK4Xwv7">rheumatoid arthritis</a>, leading to a difficult diagnosis for this disease.<a class="footnote-ref" id="fnref:82" href="#fn:82"><sup>82</sup></a> The appearance of erosions and destruction, however, is exceedingly rare and this may point instead to <a href="/facts/Rheumatoid_arthritis/qFK4Xwv7">rheumatoid arthritis</a> as a cause.<a class="footnote-ref" id="fnref:83" href="#fn:83"><sup>83</sup></a> </p><p><a href="/facts/Tendinopathy/ME5bVuKn">Diseases</a> and <a href="/facts/Tenosynovitis/Mwdl34ny">inflammation of tendons</a> have been reported in small numbers of people with RP.<a class="footnote-ref" id="fnref:84" href="#fn:84"><sup>84</sup></a> During the course of the disease, around 80% of people develop joint symptoms.<a class="footnote-ref" id="fnref:85" href="#fn:85"><sup>85</sup></a> </p> <h4>Eye</h4> <p>Involvement of the eye is rarely the initial symptom but develops in 60% of persons with RP.<a class="footnote-ref" id="fnref:86" href="#fn:86"><sup>86</sup></a><a class="footnote-ref" id="fnref:87" href="#fn:87"><sup>87</sup></a><a class="footnote-ref" id="fnref:88" href="#fn:88"><sup>88</sup></a><a class="footnote-ref" id="fnref:89" href="#fn:89"><sup>89</sup></a><a class="footnote-ref" id="fnref:90" href="#fn:90"><sup>90</sup></a> The most common forms of ocular involvement are usually mild and often consist of unilateral or bilateral <a href="/facts/Episcleritis/ADjcpdTr">episcleritis</a> and/or <a href="/facts/Scleritis/drIxNsdt">scleritis</a>, that is often anterior and could be lingering or relapsing.<a class="footnote-ref" id="fnref:91" href="#fn:91"><sup>91</sup></a><a class="footnote-ref" id="fnref:92" href="#fn:92"><sup>92</sup></a> Scleritis that is necrotizing is found to be exceedingly rare.<a class="footnote-ref" id="fnref:93" href="#fn:93"><sup>93</sup></a> Less often, <a href="/facts/Conjunctivitis/u1NJfh3A">conjunctivitis</a> occurs.<a class="footnote-ref" id="fnref:94" href="#fn:94"><sup>94</sup></a><a class="footnote-ref" id="fnref:95" href="#fn:95"><sup>95</sup></a> There are also other ocular manifestations that occur in persons with RP, these include <a href="/facts/Keratoconjunctivitis_sicca/2Q9eA0jM">keratoconjunctivitis sicca</a>, peripheral <a href="/facts/Keratitis/9pAwGjBl">keratitis</a> (rarely with ulcerations), <a href="/facts/Anterior_uveitis/le0Ns1eE">anterior uveitis</a>, <a href="/facts/Retinal_vasculitis/Lqj6lJ2C">retinal vasculitis</a>, <a href="/facts/Proptosis/GxxWrRQN">proptosis</a>, lid <a href="/facts/Edema/Q6MI3KdH">edema</a>, <a href="/facts/Keratoconus/vSL1at9P">keratoconus</a>, <a href="/facts/Retinopathy/hJNgzmdh">retinopathy</a>, <a href="/facts/Iridocyclitis/le0Ns1eE">iridocyclitis</a> and ischemic <a href="/facts/Optic_neuritis/Nhj3r878">optic neuritis</a> that can lead to blindness.<a class="footnote-ref" id="fnref:96" href="#fn:96"><sup>96</sup></a><a class="footnote-ref" id="fnref:97" href="#fn:97"><sup>97</sup></a><a class="footnote-ref" id="fnref:98" href="#fn:98"><sup>98</sup></a><a class="footnote-ref" id="fnref:99" href="#fn:99"><sup>99</sup></a> <a href="/facts/Cataract/RzN7k7K2">Cataract</a> also is reported in relation to either the disease or to <a href="/facts/Glucocorticoid/2P91Aj3S">glucocorticoid</a> exposure.<a class="footnote-ref" id="fnref:100" href="#fn:100"><sup>100</sup></a> </p> <h4>Neurological</h4> <p>The involvement of the <a href="/facts/Peripheral_nervous_system/KjVpVnHU">peripheral</a> or <a href="/facts/Central_nervous_system/k8I6To97">central nervous system</a> is relatively rare and only occurs in 3% of persons affected with RP, and is sometimes seen in a relation with concomitant vasculitis.<a class="footnote-ref" id="fnref:101" href="#fn:101"><sup>101</sup></a> The most common neurological manifestation are palsies of the <a href="/facts/Cranial_nerves/8zAVI3Ua">cranial nerves</a> V and VII. Also <a href="/facts/Hemiplegia/W44QM11N">hemiplegia</a>, <a href="/facts/Ataxia/suENWGS6">ataxia</a>, <a href="/facts/Myelitis/vYCwyU4H">myelitis</a> and <a href="/facts/Polyneuropathy/CnbsnY0J">polyneuropathy</a> have been reported in scientific literature. Very rare neurological manifestations include <a href="/facts/Aseptic_meningitis/Y7pkjqAe">aseptic meningitis</a>, <a href="/facts/Meningoencephalitis/TF8uBwla">meningoencephalitis</a>, <a href="/facts/Stroke/DwpjdzY0">stroke</a>, focal or generalized <a href="/facts/Seizures/zuIrQyze">seizures</a> and <a href="/facts/Intracranial_aneurysm/xtHmVYrt">intracranial aneurysm</a>.<a class="footnote-ref" id="fnref:102" href="#fn:102"><sup>102</sup></a><a class="footnote-ref" id="fnref:103" href="#fn:103"><sup>103</sup></a> Magnetic Resonance Imaging of the brain shows multifocal areas of enhancement consistent with <a href="/facts/Cerebral_vasculitis/REaSdJmL">cerebral vasculitis</a> in some cases.<a class="footnote-ref" id="fnref:104" href="#fn:104"><sup>104</sup></a> </p> <h4>Kidney</h4> <p>The involvement of the kidney can be caused by primary renal parenchymal lesions, or an underlying <a href="/facts/Vasculitis/rS2rP61A">vasculitis</a>, or another associated autoimmune disease. Actual kidney involvement is quite rare, elevated <a href="/facts/Creatinine/gkebqj2L">creatinine</a> levels are reported in approximately 10% of people with RP, and abnormalities in <a href="/facts/Urinalysis/PeS2UfIG">urinalysis</a> in 26%. Involvement of the kidney often indicates a worse prognosis, with a 10-year survival rate of 30%.<a class="footnote-ref" id="fnref:105" href="#fn:105"><sup>105</sup></a><a class="footnote-ref" id="fnref:106" href="#fn:106"><sup>106</sup></a><a class="footnote-ref" id="fnref:107" href="#fn:107"><sup>107</sup></a> The most common histopathologic finding is mild mesangial proliferation, that is followed by focal and segmental necrotizing <a href="/facts/Glomerulonephritis/HasrFC92">glomerulonephritis</a> with crescents. Other abnormalities that are found include <a href="/facts/Glomerulosclerosis/xIYHrtYN">glomerulosclerosis</a>, <a href="/facts/IgA_nephropathy/AoE4R6He">IgA nephropathy</a> and <a href="/facts/Interstitial_nephritis/pzdXbHxs">interstitial nephritis</a>. Immunofluorescence studies most often reveal faint deposits of C3, IgG or IgM in the primarily mesangium.<a class="footnote-ref" id="fnref:108" href="#fn:108"><sup>108</sup></a> </p> <h4>Constitutional symptoms</h4> <p>These symptoms could consist of <a href="/facts/Asthenia/U9wAgeLn">asthenia</a>, <a href="/facts/Fever/waVxR2Ac">fever</a>, <a href="/facts/Anorexia_(symptom)/G7RsaXp9">anorexia</a>, and <a href="/facts/Weight_loss/DQE4cXw0">weight loss</a>. They mostly occur during a severe disease flare.<a class="footnote-ref" id="fnref:109" href="#fn:109"><sup>109</sup></a><a class="footnote-ref" id="fnref:110" href="#fn:110"><sup>110</sup></a> </p> <h4>Others</h4> <ul><li>Skin and mucous membranes: 20 to 30% of people with relapsing polychondritis have skin involvement, including <a href="/facts/Aphthous_ulcers/Guhg6h4E">aphthous ulcers</a>, genital ulcers, and a number of non-specific skin rashes including <a href="/facts/Erythema_nodosum/bwAR5QYs">erythema nodosum</a>, <a href="/facts/Livedo_reticularis/jJ9WBGlh">livedo reticularis</a>, hives, and <a href="/facts/Erythema_multiforme/hBnYEVQY">erythema multiforme</a>.<a class="footnote-ref" id="fnref:111" href="#fn:111"><sup>111</sup></a></li> <li>Cardiovascular system: Relapsing polychrondritis may cause <a href="/facts/Aortitis/olU6I8Uh">inflammation of the aorta</a>. It can also cause leaky heart valves (<a href="/facts/Aortic_valve_regurgitation/UXB4JWg7">aortic valve regurgitation</a> in 4 to 10%, <a href="/facts/Mitral_valve_regurgitation/VEojWbau">mitral valve regurgitation</a> in 2%).<a class="footnote-ref" id="fnref:112" href="#fn:112"><sup>112</sup></a></li></ul> <h2 id="causes">Causes</h2> <p>Relapsing polychondritis is an <a href="/facts/Autoimmune_disease/sojBeQ7t">autoimmune disease</a><a class="footnote-ref" id="fnref:113" href="#fn:113"><sup>113</sup></a> in which the body's <a href="/facts/Immune_system/HRCTf1pb">immune system</a> begins to attack and destroy the <a href="/facts/Cartilage/vxy2qzKN">cartilage</a> tissues in the body. It has been postulated that both <a href="/facts/Cell-mediated_immunity/vPX39rt1">cell-mediated immunity</a> and <a href="/facts/Humoral_immunity/qG9I4pGf">humoral immunity</a> are responsible.<a class="footnote-ref" id="fnref:114" href="#fn:114"><sup>114</sup></a> </p><p>Reasons for disease onset are not known. </p> <h2 id="diagnosis">Diagnosis</h2> <p>There is no specific test for relapsing polychondritis. Some people may exhibit abnormal lab results while others may have completely normal labs even during active flares. Patients with ear, and nose chondritis with hematological abnormalities including macrocytic anemia and thrombocytopenia, should be tested for a new disease called VEXAS syndrome. </p> <h3>Diagnostic criteria</h3> <p>There are several clinical criteria used to diagnose this disease. McAdam <i>et al.</i> introduced the clinical criteria for RP in 1976.<a class="footnote-ref" id="fnref:115" href="#fn:115"><sup>115</sup></a><a class="footnote-ref" id="fnref:116" href="#fn:116"><sup>116</sup></a> These clinical criteria have later been expanded by Damiani <i>et al.</i> in 1979 and finally Michet <i>et al.</i> modified them in 1986.<a class="footnote-ref" id="fnref:117" href="#fn:117"><sup>117</sup></a><a class="footnote-ref" id="fnref:118" href="#fn:118"><sup>118</sup></a><a class="footnote-ref" id="fnref:119" href="#fn:119"><sup>119</sup></a> See the following table for these diagnostic clinical criteria and the number of conditions required for an official diagnosis. </p> <table><tbody><tr><th>Authors</th><th>Criteria</th><th>Conditions required</th></tr><tr><td>McAdam <i>et al.</i></td><td><ul><li>Bilateral auricular chondritis</li><li>Nasal chondritis</li><li>Respiratory tract chondritis</li><li>Non-erosive seronegative polyarthritis</li><li>Ocular inflammation</li><li>Audiovestibular damage</li></ul></td><td>3 out of 6 criteria</td></tr><tr><td>Damiani <i>et al.</i></td><td><ul><li>Bilateral auricular chondritis (A)</li><li>Nasal cartilage inflammation (A)</li><li>Respiratory tract chondritis (A)</li><li>Non-erosive sero-negative polyarthritis (A)</li><li>Ocular inflammation (A)</li><li>Audiovestibular involvement (A)</li><li>Histologic confirmation (B)</li><li>Positive response to corticosteroids or dapsone (C)</li></ul></td><td><ul><li>3 (A) criteria or</li><li>1 (A) and (B) or</li><li>2 (A) criteria and (C)</li></ul></td></tr><tr><td>Michet <i>et al.</i></td><td><ul><li>Auricular cartilage inflammation (A)</li><li>Nasal cartilage inflammation (A)</li><li>Laryngotracheal cartilage inflammation (A)</li><li>Ocular inflammation (B)</li><li>Hearing loss (B)</li><li>Vestibulary dysfunction (B)</li><li>Sero-negative arthritis (B)</li></ul></td><td><ul><li>2 out of 3 (A) criteria or</li><li>1 out of 3 (A) criteria and 2 (B) criteria</li></ul></td></tr></tbody></table> <h3>Laboratory findings</h3> <p>Patients presenting with acute episodes often have high levels of inflammatory markers such as erythrocyte sedimentation rate or C-reactive protein, ESR or CRP. Patients often have cartilage-specific antibodies present during acute relapsing polychondritis episodes. Antinuclear antibody reflexive panel, rheumatoid factor, and antiphospholipid antibodies are tests that may assist in the evaluation and diagnosis of autoimmune connective-tissue diseases. </p> <h3>Imaging studies</h3> <p>FDG <a href="/facts/Positron_emission_tomography/5SmcW6qz">positron emission tomography</a> (PET) may be useful to detect the condition early.<a class="footnote-ref" id="fnref:120" href="#fn:120"><sup>120</sup></a> Other imaging studies including MRI, CT scans, and X-rays may reveal inflammation and/or damaged cartilage facilitating diagnosis. </p> <h3>Special tests</h3> <h4>Biopsy</h4> <p>Biopsy of the cartilage tissue (for example, ear) may show tissue inflammation and destruction, however is not helpful the diagnosis. The Biopsy of cartilage in patients with relapsing polychondritis may demonstrate <a href="/facts/Chondrolysis/ahBpkcsq">chondrolysis</a>, <a href="/facts/Chondritis/7LUHnHPy">chondritis</a>, and perichondritis. </p> <h4>Pulmonary function tests</h4> <p>Are usually not useful, in most cases changes on the pulmonary function test will not correlate with tracheomalacia, therefore findings on the full set of <a href="/facts/Pulmonary_function_tests/GgLVssa6">pulmonary function tests</a>, including inspiratory and expiratory flow-volume loops usually represent late disease. Patterns consistent with either extrathoracic or intrathoracic obstruction (or both) may occur in this disease. Pulmonary function tests (flow-volume loops) provide a useful noninvasive means of quantifying and following the degree of extrathoracic airway obstruction in relapsing polychondritis.<a class="footnote-ref" id="fnref:121" href="#fn:121"><sup>121</sup></a> </p> <h3>Differential diagnosis</h3> <p>A differential diagnosis should be taken into account with the following main RP manifestations.<a class="footnote-ref" id="fnref:122" href="#fn:122"><sup>122</sup></a> </p> <table><tbody><tr><th>Manifestation of RP</th><th>Differential diagnosis</th></tr><tr><td>Arthritis</td><td><a href="/facts/Rheumatoid_arthritis/qFK4Xwv7">Rheumatoid arthritis</a>.</td></tr><tr><td>Auricular chondritis</td><td>Infectious <a href="/facts/Perichondritis/geVWSnwh">perichondritis</a>, <a href="/facts/Injury/PJ7CbnMQ">injury</a>, <a href="/facts/Insect_bites_and_stings/KbmgfcCc">insect bites and stings</a>, ear <a href="/facts/Erysipelas/c9SMNUWw">erysipelas</a>, <a href="/facts/Cystic_chondromalacia/xrbCTY6U">cystic chondromalacia</a>, overexposure to extreme cold temperatures or to sunlight, <a href="/facts/Frostbite/jUf83CpY">frostbite</a> of the ear, <a href="/facts/Congenital_syphilis/5oCKt60X">congenital syphilis</a>.</td></tr><tr><td>Airway/kidney involvement</td><td><a href="/facts/Granulomatosis_with_polyangiitis/TPu4mHpD">Granulomatosis with polyangiitis</a>, <a href="/facts/Bronchial_asthma/7GkJvxn3">bronchial asthma</a>.</td></tr><tr><td>Nose cartilage involvement/saddle nose</td><td>Granulomatosis with polyangiitis, <a href="/facts/Leishmaniasis/L5v8Thy1">leishmaniasis</a>, <a href="/facts/Congenital_syphilis/5oCKt60X">congenital syphilis</a>, <a href="/facts/Leprosy/FSjTpMEB">leprosy</a>, <a href="/facts/Aspergillosis/yBJUalj8">aspergillosis</a>, <a href="/facts/Paracoccidioidomycosis/wm4bePCK">paracoccidioidomycosis</a>, <a href="/facts/Cocaine/rdQP4zwF">cocaine</a> inhalation, <a href="/facts/Systemic_lupus_erythematosus/kfHYawre">systemic lupus erythematosus</a>.</td></tr><tr><td>Subglottic stenosis</td><td>Prior endotracheal intubation, <a href="/facts/Amyloidosis/FeuTXVdn">amyloidosis</a>, <a href="/facts/Sarcoidosis/qgV7Uoe8">sarcoidosis</a>.</td></tr><tr><td>Vascular involvement</td><td><a href="/facts/Takayasu%2527s_arteritis/tM6FJSpd">Takayasu's arteritis</a>, <a href="/facts/Polyarteritis_nodosa/RbFBUVKG">polyarteritis nodosa</a>, <a href="/facts/Beh%25C3%25A7et%2527s_disease/oah5LIcL">Behçet's disease</a>, <a href="/facts/Antiphospholipid_syndrome/8R4fk5FP">antiphospholipid syndrome</a>.</td></tr><tr><td>Vestibular disease</td><td><a href="/facts/Posterior_circulation_infarct/Eau5k1x4">Posterior circulation infarct</a>, vestibulitis, <a href="/facts/Benign_paroxysmal_vertigo/qswT04wk">benign paroxysmal vertigo</a>, <a href="/facts/M%25C3%25A9ni%25C3%25A8re%2527s_disease/rUkGKElL">Ménière's disease</a>.</td></tr></tbody></table> <h2 id="treatment">Treatment</h2> <p>There are no prospective randomized controlled trials studying therapies for relapsing polychondritis. Evidence for efficacy of treatments is based on many case reports and series of small groups of patients. There are case reports that non-steroidal anti-inflammatories are effective for mild disease and that corticosteroids are effective for treatment of severe relapsing polychondritis. There are multiple case reports that <a href="/facts/Dapsone/0d1BGd1n">dapsone</a> is effective in doses from 25 mg/day to 200 mg/day.<a class="footnote-ref" id="fnref:123" href="#fn:123"><sup>123</sup></a> Corticosteroid-sparing medications such as <a href="/facts/Azathioprine/CmeIK3ca">azathioprine</a> or <a href="/facts/Methotrexate/LoDvhRKX">methotrexate</a> may be used to minimize steroid doses and limit the side effects of steroids. For severe disease <a href="/facts/Cyclophosphamide/eTXHmLFV">cyclophosphamide</a> is often given in addition to high dose intravenous steroids.<a class="footnote-ref" id="fnref:124" href="#fn:124"><sup>124</sup></a> </p> <h2 id="prognosis">Prognosis</h2> <p>Many individuals have mild symptoms, which recur infrequently, while others may have persistent problems that become debilitating or life-threatening.<a class="footnote-ref" id="fnref:125" href="#fn:125"><sup>125</sup></a> </p> <h2 id="epidemiology">Epidemiology</h2> <p>Relapsing polychondritis occurs as often in men as in women. In a Mayo Clinic series, the annual incidence was about 3.5 cases per million. The highest incidence is between the ages of 40 and 50 years, but it may occur at any age.<a class="footnote-ref" id="fnref:126" href="#fn:126"><sup>126</sup></a> </p> <h2 id="history">History</h2> <p>In 1923, <a href="/facts/Rudolf_von_Jaksch/Ttxovpcu">Rudolf Jaksch von Wartenhorst</a> first discovered relapsing polychondritis while working in Prague and initially named it <i>Polychondropathia</i>.<a class="footnote-ref" id="fnref:127" href="#fn:127"><sup>127</sup></a><a class="footnote-ref" id="fnref:128" href="#fn:128"><sup>128</sup></a> </p> <p>His patient was a 32-year-old male brewer who presented with fever, asymmetric polyarthritis, and the ears and nose showed signs of swelling, deformity and were painful. Biopsy of nasal cartilage revealed loss of the cartilage matrix and a hyperplastic mucous membrane. Jaksch von Wartenhorst considered this was an undescribed degenerative disorder of cartilage and named it Polychondropathia. He even took his patient's occupation into consideration, and related the cause to excessive alcohol intake.<a class="footnote-ref" id="fnref:129" href="#fn:129"><sup>129</sup></a> </p><p>Since then, the disease has received many names. The following table shows the history of the nomenclature of relapsing polychondritis. The current name, Relapsing Polychondritis (RP), was introduced by Pearson and his colleagues in 1960 to emphasize the episodic course of the disease.<a class="footnote-ref" id="fnref:130" href="#fn:130"><sup>130</sup></a><a class="footnote-ref" id="fnref:131" href="#fn:131"><sup>131</sup></a> </p> <table><tbody><tr><th>Suggested name</th><th>Author(s) and year</th></tr><tr><td>Polychondropathia</td><td>Rudolf Jaksch von Wartenhorst in 1923</td></tr><tr><td>Chondromalacia</td><td>Von Meyenburg in 1936 and Altherr in 1936</td></tr><tr><td>Panchondritis</td><td>Harders in 1954</td></tr><tr><td>Polychondritis chronica atrophicans</td><td>Bober and Czarniecki in 1955</td></tr><tr><td>Chronic atrophic polychondritis</td><td>Bean, Drevets, and Chapman in 1958</td></tr><tr><td>Relapsing polychondritis</td><td>Pearson, Kline, and Newcomer in 1960</td></tr><tr><td>Atrophic polychondritis</td><td>Rhys Davies and Kelsall in 1961</td></tr></tbody></table> <h2 id="research">Research</h2> <p>In 2017 a physician also a patient with the disease became a rheumatologist to study the disease. Since then there have been increase in awareness as well as different studies that helping to advance the field. There has been little research on neurological problems related to RP.<a class="footnote-ref" id="fnref:132" href="#fn:132"><sup>132</sup></a> If these cartilage structures get inflamed, they could press against nerves and cause a variety of problems that is seen in RP like <a href="/facts/Peripheral_neuropathy/2KjA7nyD">peripheral neuropathy</a> and many more.<a class="footnote-ref" id="fnref:133" href="#fn:133"><sup>133</sup></a><a class="footnote-ref" id="fnref:134" href="#fn:134"><sup>134</sup></a> </p> <h2 id="further-reading">Further reading</h2> <ul><li>Sanders, Lisa (14 November 2021) [10 November 2021 (online)]. <a href="https://www.nytimes.com/2021/11/10/magazine/relapsing-polychondritis-diagnosis.html">"A Doctor Asks Two Strange Questions That Reveal a Mysterious Disease"</a>. <i><a href="/facts/The_New_York_Times_Magazine/AQhGYeFC">The New York Times Magazine</a></i>. p. 22. Retrieved 10 November 2021.</li> <li>Trentham DE, Le CH (July 1998). <a href="https://web.archive.org/web/20141108174013/http://rpolychondritis.tripod.com/DRTrentham.html">"Relapsing polychondritis"</a>. <i>Ann. Intern. Med</i>. 129 (2): 114–22. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.7326%2F0003-4819-129-2-199807150-00011">10.7326/0003-4819-129-2-199807150-00011</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9669970">9669970</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:31763543">31763543</a>. Archived from <a href="http://rpolychondritis.tripod.com/DRTrentham.html">the original</a> on 2014-11-08. Retrieved 2006-06-20.</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Puéchal, X; Terrier, B; Mouthon, L; Costedoat-Chalumeau, N; Guillevin, L; Le Jeunne, C (March 2014). "Relapsing polychondritis". Joint Bone Spine. 81 (2): 118–24. doi:10.1016/j.jbspin.2014.01.001. PMID 24556284. S2CID 205754989. <a href="http://www.hal.inserm.fr/inserm-00951203" target="_blank">http://www.hal.inserm.fr/inserm-00951203</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Langford, Carol A. (2015). Harrison's Principles of Internal Medicine (19th ed.). New York, NY: McGraw-Hill. p. 389: Relapsing Polychondritis. ISBN 978-0-07-1802161. <a href="978-0-07-1802161" target="_blank">978-0-07-1802161</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Langford, Carol A. (2015). Harrison's Principles of Internal Medicine (19th ed.). New York, NY: McGraw-Hill. p. 389: Relapsing Polychondritis. ISBN 978-0-07-1802161. <a href="978-0-07-1802161" target="_blank">978-0-07-1802161</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Langford, Carol A. (2015). Harrison's Principles of Internal Medicine (19th ed.). New York, NY: McGraw-Hill. p. 389: Relapsing Polychondritis. ISBN 978-0-07-1802161. <a href="978-0-07-1802161" target="_blank">978-0-07-1802161</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Langford, Carol A. (2015). Harrison's Principles of Internal Medicine (19th ed.). New York, NY: McGraw-Hill. p. 389: Relapsing Polychondritis. ISBN 978-0-07-1802161. <a href="978-0-07-1802161" target="_blank">978-0-07-1802161</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>Langford, Carol A. (2015). Harrison's Principles of Internal Medicine (19th ed.). New York, NY: McGraw-Hill. p. 389: Relapsing Polychondritis. ISBN 978-0-07-1802161. <a href="978-0-07-1802161" target="_blank">978-0-07-1802161</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></p></li> <li id="fn:18"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></p></li> <li id="fn:19"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></p></li> <li id="fn:20"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:20" class="footnote-back-ref">↩</a></p></li> <li id="fn:21"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:21" class="footnote-back-ref">↩</a></p></li> <li id="fn:22"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:22" class="footnote-back-ref">↩</a></p></li> <li id="fn:23"><p>Langford, Carol A. (2015). Harrison's Principles of Internal Medicine (19th ed.). New York, NY: McGraw-Hill. p. 389: Relapsing Polychondritis. ISBN 978-0-07-1802161. <a href="978-0-07-1802161" target="_blank">978-0-07-1802161</a> <a href="#fnref:23" class="footnote-back-ref">↩</a></p></li> <li id="fn:24"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:24" class="footnote-back-ref">↩</a></p></li> <li id="fn:25"><p>Langford, Carol A. (2015). Harrison's Principles of Internal Medicine (19th ed.). New York, NY: McGraw-Hill. p. 389: Relapsing Polychondritis. ISBN 978-0-07-1802161. <a href="978-0-07-1802161" target="_blank">978-0-07-1802161</a> <a href="#fnref:25" class="footnote-back-ref">↩</a></p></li> <li id="fn:26"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:26" class="footnote-back-ref">↩</a></p></li> <li id="fn:27"><p>Langford, Carol A. (2015). Harrison's Principles of Internal Medicine (19th ed.). New York, NY: McGraw-Hill. p. 389: Relapsing Polychondritis. ISBN 978-0-07-1802161. <a href="978-0-07-1802161" target="_blank">978-0-07-1802161</a> <a href="#fnref:27" class="footnote-back-ref">↩</a></p></li> <li id="fn:28"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:28" class="footnote-back-ref">↩</a></p></li> <li id="fn:29"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:29" class="footnote-back-ref">↩</a></p></li> <li id="fn:30"><p>Langford, Carol A. (2015). Harrison's Principles of Internal Medicine (19th ed.). New York, NY: McGraw-Hill. p. 389: Relapsing Polychondritis. ISBN 978-0-07-1802161. <a href="978-0-07-1802161" target="_blank">978-0-07-1802161</a> <a href="#fnref:30" class="footnote-back-ref">↩</a></p></li> <li id="fn:31"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:31" class="footnote-back-ref">↩</a></p></li> <li id="fn:32"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:32" class="footnote-back-ref">↩</a></p></li> <li id="fn:33"><p>Langford, Carol A. (2015). Harrison's Principles of Internal Medicine (19th ed.). New York, NY: McGraw-Hill. p. 389: Relapsing Polychondritis. ISBN 978-0-07-1802161. <a href="978-0-07-1802161" target="_blank">978-0-07-1802161</a> <a href="#fnref:33" class="footnote-back-ref">↩</a></p></li> <li id="fn:34"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. PMID 24461536. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:34" class="footnote-back-ref">↩</a></p></li> <li id="fn:35"><p>Cantarini, L; Vitale, A; Brizi, MG; Caso, F; Frediani, B; Punzi, L; Galeazzi, M; Rigante, D (2014). "Diagnosis and classification of relapsing polychondritis". Journal of Autoimmunity. 48–49: 53–9. doi:10.1016/j.jaut.2014.01.026. 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