Overlapping Clinical Syndromes in Patients with Glial Fibrillary Acidic Protein IgG.

OBJECTIVE: The aim of this paper is to report 2 cases with overlapping syndromes in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. METHODS: Antibodies were detected by indirect immunofluorescence assay. Patient data were analyzed retrospectively. RESULTS: One patient presented with overlapping neuromyelitis optica spectrum disorder (NMOSD) and positive GFAP-IgG and aquaporin-4-IgG. His main symptoms included vision loss, hiccups, fever, headache, and ataxia. High leukocyte count and protein levels were found in cerebrospinal fluid. Brain magnetic resonance imaging (MRI) revealed abnormalities in the hippocampus, midbrain, pons, medulla, and meninges. Characteristic radial enhancing patterns were seen. The other patient was a male with relapsing polychondritis (RP) and positive GFAP-IgG. His main manifestations were meningoencephalitis and dementia. MRI showed extensive abnormalities in the white matter around the ventricles, temporal lobe, and thalamus, with enhancement. Both patients responded well to the treatment with steroids and immunosuppressants. CONCLUSIONS: Although overlapping syndromes are rare, we report positive GFAP-IgG in 2 cases with NMOSD or RP. Both patients had clinical features of GFAP astrocytopathy, but diagnosis of the condition was very challenging because of the overlapping presentation.

Case report of mixed-type autoimmune hemolytic anemia in a patient with relapsing polychondritis.

RATIONALE: Relapsing polychondritis (RP) is a rare autoimmune-related disease and may be associated with other autoimmune diseases. PATIENT CONCERNS: Here we reported a case of RP patients with mixed-type AIHA. The patient was diagnosed with RP in March 2008 which was treated and the patient was in stable condition. Laboratory data revealed progressive decrease in hemoglobin during her hospitalization due to pulmonary infection in 2016. Positive Coombs' test and moderate titer of anti-cold agglutinin was detected. DIAGNOSIS: Mixed-type AIHA was diagnosed as a comorbidity in this case given the circumstance that her RP was stable and low-dose oral corticosteroids was enough to maintain remission. INTERVENTIONS: The patient was treated with intravenous immunoglobulin and steroids. OUTCOMES: The patient's body temperature dropped and hemoglobin levels rose in 2 weeks. LESSONS: Reports of RP patients with autoimmune hemolytic anemia (AIHA) are extremely rare and cases with the mixed-type AIHA has not been reported. Here we describe a case of RP with mixed-type AIHA which was considered as a comorbidity rather than a complication.

Propionate-producing bacteria in the intestine may associate with skewed responses of IL10-producing regulatory T cells in patients with relapsing polychondritis.

Relapsing polychondritis (RP) is an inflammatory disease of unknown causes, characterized by recurrent inflammation in cartilaginous tissues of the whole body. Recently, researchers have reported that, in mouse experiments, altered gut microbe-dependent T cell differentiation occurred in gut associated lymphoid tissues. Here, we investigated whether gut microbe alteration existed, and if so, the alteration affected peripheral T cell differentiation in patients with RP. In an analysis of gut microbiota, we found increased annotated species numbers in RP patients compared with normal individuals. In the RP gut microbiota, we observed several predominant species, namely Veillonella parvula, Bacteroides eggerthii, Bacteroides fragilis, Ruminococcus bromii, and Eubacterium dolichum, all species of which were reported to associate with propionate production in human intestine. Propionate is a short-chain fatty acid and is suggested to associate with interleukin (IL)10-producing regulatory T (Treg) cell differentiation in gut associated lymphoid tissues. IL10 gene expressions were moderately higher in freshly isolated peripheral blood mononuclear cells (PBMC) of RP patients than those of normal individuals. Six hours after the initiation of the cell culture, regardless of the presence and absence of mitogen stimulation, IL10 gene expressions were significantly lower in RP patients than those in normal individuals. It is well known that PBMC of patients with autoimmune and inflammatory diseases show hyporesponsiveness to mitogen stimulation. We suggest that, in RP patients, continuous stimulation of intestinal T cells by excessive propionate leads to the spontaneous IL10 production and a subsequent refractory period of T cells in patients with RP. The hyporesponsiveness of Treg cells upon activation may associate with inflammatory cytokine production of PBMC and subsequently relate to chondritis in RP patients.

Remission of relapsing polychondritis after successful treatment of myelodysplastic syndrome with azacitidine: a case and review of the literature.

BACKGROUND: Relapsing polychondritis (RP) is a rare autoimmune disorder, and myelodysplastic syndrome (MDS) is accompanied by RP at variable rates. Herein, we report a case with RP and MDS who responded dramatically to 5-azacitidine for MDS. CASE PRESENTATION: With conventional immunosuppressive treatment, our patient had several episodes of different side effects, including infections. With the diagnosis of MDS and initiation of azacitidine treatment, all the manifestations of RP disappeared, and remission was achieved for MDS. Although he had relapses of either RP or MDS after several years of azacitidine treatment, all relapses were controlled well with the initiation of azacitidine treatment every time. CONCLUSIONS: Azacitidine should be kept in mind as a treatment option for RP patients with MDS.

Relapsing polychondritis associated with psoriasis vulgaris successfully treated with adalimumab: A case report with published work review.

Relapsing polychondritis (RP) is a rare autoimmune-mediated disease characterized by inflammation involving cartilaginous tissues. We report here a case of RP in a 38-year-old Japanese man with 13-year duration of psoriasis vulgaris treated with topical steroids and vitamin D3 . The patient presented with tender swelling and erythema of both auricles, and the antibody to type II collagen was detected. The biopsy specimen revealed a dense mixed cell infiltration over the auricular cartilage. We reviewed eight cases with the association of RP and psoriasis, and in all cases the clinical course of psoriasis did not correlate with that of RP. The severity of RP was mild in the majority of cases, and our case was unique in that the patient had no joint symptoms. Adalimumab treatment was effective for both RP and psoriasis. Fat-suppressed contrast-enhanced magnetic resonance imaging was beneficial, not only to demonstrate subclinical inflammation in the nasal septum, but also to subjectively assess the improvement of RP.

Corticosteroid Therapy for a Patient with Relapsing Polychondritis Complicated by IgG4-Related Disease.

Relapsing polychondritis (RP) is a rare systemic disorder characterized by recurrent, widespread chondritis of the auricular, nasal, and tracheal cartilages. IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease characterized by the infiltration of IgG4-bearing plasma cells into systemic organs. Although 25% to 35% of patients with RP have a concurrent autoimmune disease, coexistence of RP and IgG4-RD is rare. We herein report a case of RP complicated by IgG4-RD. A 63-year-old man developed recurrent bilateral ear pain and swelling, recurrent blurred and decreased vision, and migratory multiple joint pain, sequentially within one year. Fourteen months after the first symptom, he experienced dry cough and dyspnea with exertion. A computed tomography (CT) scan detected interstitial pneumonia, swelling of bilateral submandibular glands, bilateral hilar and mediastinal lymphadenopathy, and several nodules in bilateral kidneys. His serum levels of IgG and IgG4 were elevated. The biopsy specimen of auricular cartilage showed infiltrations of inflammatory cells and fibrosis consistent with RP. The IgG4-positive cells were not observed in auricular cartilage. The patient met the diagnostic criteria of RP, including bilateral auricular chondritis, conjunctivitis, iritis and polyarthritis. The biopsy specimens of lung and kidney revealed the significant infiltrations of IgG4-positive plasma cells and fibrosis. We also diagnosed him as having IgG4-RD, affecting bilateral submandibular glands, hilar and mediastinal lymph nodes, lungs, and kidneys. Thus, RP preceded the onset of IgG4-RD. Corticosteroid therapy improved the symptoms and CT scan findings. In conclusion, RP and IgG4-RD do coexist; however, the pathogenesis of their coexistence is unknown.

Relapsing polychondritis.

Relapsing polychondritis (RP) is a rare disease in which recurrent bouts of inflammation, in some cases followed by destruction, affect the cartilage of the ears, nose, larynx, and tracheobronchial tree. At presentation, however, arthritis is the most common manifestation and more than half the patients have no evidence of chondritis. The subsequent development of chondritis provides the correct diagnosis in patients who present with polyarthritis, ocular inflammation, or skin or audiovestibular manifestations of unknown origin. A concomitant autoimmune disease is present in one-third of patients with RP. The pathogenesis of RP involves an autoimmune response to as yet unidentified cartilage antigens followed by cartilage matrix destruction by proteolytic enzymes. The diagnosis rests on clinical grounds and can benefit from use of Michet's criteria. Anti-collagen type II and anti-matrilin-1 antibodies are neither sensitive nor specific and consequently cannot be used for diagnostic purposes. In addition to the physical evaluation and laboratory tests, useful investigations include dynamic expiratory computed tomography, magnetic resonance imaging, Doppler echocardiography, and lung function tests. Bronchoscopy has been suggested as a helpful investigation but can worsen the respiratory dysfunction. The treatment of RP is not standardized. The drug regimen should be tailored to each individual patient based on disease activity and severity. Glucocorticoid therapy is the cornerstone of the treatment of RP and is used chronically in most patients. Immunosuppressive agents are given to patients with severe respiratory or vascular involvement and to those with steroid-resistant or steroid-dependent disease. Methotrexate is often effective. Cyclophosphamide is used in severe forms.

Pathogenesis of relapsing polychondritis: a 2013 update.

Relapsing polychondritis (RP) is a systemic inflammatory disease primarily affecting not only the cartilaginous structures of the ears, nose and tracheobronchial tree but also the joints, the inner ear, the eyes, and the cardiovascular system. RP is an immune-mediated disease during which target antigens are still unknown, but data from human studies and murine models strongly support a role of both Collagen Type II (CII) and matrilin-1 as potential candidates. RP is likely a Th1-mediated disease as serum levels of interferon (IFN)-γ, interleukin [IL]-12, and IL-2 parallel changes in disease activity, while the levels of Th2 cytokines do not. Serum levels of sTREM-1, interferon-γ, CCL4, vascular endothelial growth factor, and matrix metalloproteinases-3 are significantly higher in RP patients than in healthy donors, with sTREM-1 correlating with disease activity. Patients with active RP also have significantly higher levels of MCP-1, MIP-1ß, MIF, and IL-8 than controls. These pro-inflammatory chemokines are involved in the modulation and recruitment of monocytes and neutrophils. Altogether, these data suggest that a complex cytokine network orchestrates the recruitment of infiltrating cells in RP lesions. Cytokine modulation using TNFα blockers, rituximab, anakinra, tocilizumab, and abatacept has recently been shown effective in some RP cases but further data are needed. Better understanding of the repertoire of infiltrating cells may provide interesting clues to further define the putative RP auto-antigens. Study of circulating mononuclear cells during RP flares may also provide crucial information about the ongoing cellular trafficking and recruitment processes involved in this rare disease.

Biologics in relapsing polychondritis: a case series.

OBJECTIVES: To describe the effects of biologics in an unbiased series of relapsing polychondritis cases. METHODS: We extracted all the cases encoded 'polychondritis' from the computerized medical files of our department. The relapsing polychondritis diagnosis was confirmed using Damiani's criteria. Patients treated with biologics were evaluated for efficacy and adverse drugs reactions until October 2012. RESULTS: Nine patients were exposed to 22 biologics as corticosteroid-sparing drugs. Biologics were used at the same doses as in rheumatoid arthritis. Mean duration of exposure to biologics was 28 months. A TNF-antagonist was most frequently used as first-line biologic therapy (7/9), leading to partial or complete efficacy in six cases (85.7%). Loss of efficacy occurred in 5 cases. Abatacept (n=3) and tocilizumab (n=2) were effective as second-line biologic therapy while anakinra (n=2) and certolizumab (n=1) were not. Seven serious adverse drug reactions occurred, including 5 infections. CONCLUSIONS: TNF-α antagonists may be proposed earlier in relapsing polychondritis to spare corticosteroids. Switching to another biologic can be proposed in case of loss of efficacy. Tocilizumab or abatacept can be proposed as third-line therapy. The benefit-to-risk ratio of biologics in relapsing polychondritis should be evaluated prospectively.

Relapsing polychondritis complicated by giant cell myocarditis and myositis.

An 83-year-old man presented with a three-week history of dyspnea. The clinical features suggested a diagnosis of relapsing polychondritis (RP); however, the patient died of heart failure. An autopsy revealed active chondritis of the tracheal and bronchial cartilage. Furthermore, giant cell myocarditis (GCM) and myositis were detected. To the best of our knowledge, this represents the first report of RP complicated by GCM and myositis. In patients with RP, GCM and myositis, CD163-positive macrophages and T-cells are most common, and the T-cell subset exhibits CD8 predominance. Common mechanisms of tissue damage caused by cytotoxic T-cells are likely to contribute to RP, GCM and myositis.

Successful treatment with noninvasive positive-pressure ventilation based on the prediction of disease onset using CT and respiratory function tests in an elderly patient with relapsing polychondritis.

An 83-year-old man who had been receiving treatment for bronchial asthma since 62 years of age experienced difficulty breathing on exertion and was admitted to the hospital. On admission, computed tomography revealed tracheal wall thickening, while test results for antinuclear antibodies and anti-type II collagen antibodies were positive. Since a saddle nose deformity, malacia of the auricles and sensorineural deafness were also observed, relapsing polychondritis was diagnosed. Measuring the peak expiratory flow rate was useful in the early airway assessment. During the follow-up period, the patient's dyspnea worsened and noninvasive positive-pressure ventilation was introduced. As a result, the subjective symptoms improved.

Occurrence of relapsing polychondritis with a rising cANCA titre in a cANCA-positive systemic and cerebral vasculitis patient.

Relapsing polychondritis (RP) is a relatively rare disorder, with a high death rate that affects cartilaginous structures. RP can be either primary or secondary as part of autoimmune syndromes. We present a case of RP in a 49-year-old man suffering from cytoplasmic antineurophil cytoplasmic antibodies (cANCA) positive vasculitis, admitted to our hospital with red swollen left ear and painful sternoclavicular joint and larynx. The patient was in remission from the vasculitis but manifested a high cANCA titre indicating vasculitis activity. With his high cANCA titre vasculitis, full manifestation of RP concomitantly occurred. After a successful cortisone treatment for RP, the patient received cyclophosphamide treatment for his vasculitis that resulted in a decrease in cANCA titre and full remission of his RP symptoms.

[Airway involvement in relapsing polychondritis].

Relapsing Polychondritis (RP) is an uncommon, chronic, and potentially life-threatening multisystem disorder characterized by recurrent inflammatory episodes affecting the cartilaginous tissues of the external ears, nose, peripheral joints, larynx and tracheobronchial tree, sometimes leading to their destruction. RP can also inflame other proteoglycan-rich structures, such as the eye, heart, blood vessels and inner ears. Systemic symptoms are common, and vasculitis affecting skin or internal organs may occur. The etiology of RP is still unknown, but the pathogenetic role of the autoimmunity is suggested by frequent overlaps with various autoimmune diseases, and by the presence of autoantibody against cartilage in the serum of patients with RP. Although several reports have demonstrated the clinicopathologic manifestations and radiologic findings of RP, there are no specific features of RP. Therefore, it is difficult to show the diagnosis of RP. Airway involvements are major causes of morbidity and mortality, and they have accounted for most of the deaths due to RP. To suppress the inflammation of airway mucosa and cartilage is extremely important in the successful treatment for RP. Above all, earlier diagnosis would lead to better outcomes.

Patients with relapsing polychondritis and previous cartilage trauma present more autoimmunity phenomena.

Relapsing polychondritis (RP) is an autoimmune disease characterized by inflammation and destruction of all type of body cartilage, and the cartilage trauma may be a trigger of the disease in a susceptible person. We describe the clinical and laboratory findings in a group of 18 patients with RP with (7 cases) or without (11 cases) anteceding cartilage trauma. The mean age was 41 years in the group with cartilage trauma and 55 years in the group without cartilage trauma. For both groups, female gender was predominant. All patients presented with auricular chondritis. Systemic manifestations and autoimmunity were more common in patients with anteceding trauma.