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Hyper IgG4-Related Disease Presenting with Orbital Tumor and Immune Deficiency

Hyper IgG4-Related Disease Presenting with Orbital Tumor and Immune Deficiency Hindawi Case Reports in Immunology Volume 2021, Article ID 9260051, 5 pages https://doi.org/10.1155/2021/9260051 Case Report Hyper IgG4-Related Disease Presenting with Orbital Tumor and Immune Deficiency 1 2 Caroline G. Olson and Nancy Y. Olson University of Missouri-Kansas City, School of Medicine, Kansas City, MO, USA Allergy and Rheumatology Clinic of Kansas City, Overland Park, KS, USA Correspondence should be addressed to Caroline G. Olson; carolinegolson@gmail.com Received 2 July 2021; Accepted 2 September 2021; Published 20 September 2021 Academic Editor: Ahmad Mansour Copyright © 2021 Caroline G. Olson and Nancy Y. Olson. 'is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We report a case of IgG4-RD in a patient with high IgG4 levels, low functional antibodies, and low IgM levels. He presented with bilateral orbital pseudotumors and, after initial improvement on corticosteroids, relapsed with recurrent pleural effusion and pelvic pseudotumor. He had a grossly elevated serum IgG (1905 mg/dl) with elevations in all IgG subclasses but marked elevation in IgG4 (412 mg/dl), low IgM, and low pneumococcal antibodies. Orbital mass biopsy showed polyclonal lymphocytic infiltration and increased IgG4 plasma cells. 'e patient was started on prednisone and tried several immunosuppressive medications including mycophenolate mofetil, methotrexate, hydroxychloroquine, and azathioprine with decrease in size of the orbital pseudotumor. During a period when the patient stopped his medications, the pseudotumor enlarged with new development of recurrent pleural effusions. He was also found to have a pelvic mass that was biopsy positive for IgG4 proliferation. 'is case with progression to multiorgan involvement highlights the importance of identifying patients with IgG4-related disease. In contrast to previous cases with normal-to-high IgM, the IgM was low with impaired functional antibodies. and aortitis, head and neck limited, and systemic with 1. Introduction salivary or lacrimal gland swelling (Mikulicz disease) Immunoglobulin G4-related disease (IgG4-RD) is a rare [1, 8–10]. One study found that IgG4 played a role in all relapsing-remitting fibroinflammatory disease caused by archival cases of idiopathic retroperitoneal fibrosis analyzed monoclonal proliferation of IgG4+ plasma cells and dense [4]. Atypical presentations including tubulointerstitial ne- lymphoplasmacytic infiltration with reversible collagen phritis, glomerulonephritis, perineural disease, prostatitis, deposition [1–3]. It typically presents with insidious onset in orchitis, sclerosing mastitis, eosinophilic angiocentric fi- middle-aged to elderly men, although studies have shown brosis, interstitial lung disease, and pleural and pericardial higher IgG4 levels and worse disease in Asian populations effusions have been reported [1, 11, 12]. Intrathoracic in- [1, 3–5]. IgG4+ plasma cells produce antibodies that may volvement can include parenchymal opacities and interstitial lung disease, tracheobronchial stenosis, fibrosing media- regulate the immune system and protect against hyper- sensitivity anaphylaxis in patients with allergies [6, 7]. Pa- stinitis, nodular pleural lesions, and rarely, pleural effusion tients often have a longstanding history of allergic rhinitis, and may resemble sarcoidosis or lung cancer [3, 13]. Salivary bronchial asthma, or eczema at diagnosis. IgG4- RD can be and lacrimal gland involvement can cause facial and orbital asymptomatic or present with symptoms of mechanical swelling and can present similarly to Sjogren’s syndrome compression exerted by pseudotumor-like fibrotic masses. with sclerosing sialadenitis [1, 14]. Orbital pseudotumors 'e most common manifestations have been grouped into involve the lacrimal gland in 69% of cases but can also occur four clinical phenotypes including pancreatobiliary (type 1 in extraocular muscles, palpebrae, optic nerve, and orbital autoimmune pancreatitis (AIP)), retroperitoneal fibrosis bone, as well causing exophthalmos and restriction of ocular 2 Case Reports in Immunology movements [1, 15–17]. 'ese orbital manifestations tend to 'ree of 14 pneumococcal antibody titers were at a pro- have higher relapse rates on steroids and overall have higher tective level (>1.3 mcg/ml). Haemophilus influenza anti- bodies were decreased at 0.34. Angiotensin-converting cumulative doses of corticosteroids [10]. Several studies have shown a link between lacrimal gland involvement and de- enzyme (ACE) was low. Rheumatoid factor was positive at velopment of lymphoma [18]. 'e 2019 ACR/EULAR 28, and cyclic citrullinated peptide (CCP) was negative. standards for diagnosis of IgG4-RD are based on the 'e patient was started on prednisone 20 mg daily, and presence of characteristic clinical or radiological involve- to decrease steroid need with his weight, mycophenolate ment of a typical organ or pathological evidence of an in- mofetil 1000 mg BID was added. Mycophenolate was dis- flammatory lymphoplasmacytic infiltrate of uncertain continued due to side effects of dizziness and nausea. He was etiology. In addition, the patients must not have another dissatisfied with steroid weight gain at prednisone 20 mg explanation for their symptoms including infection, auto- daily (BMI had increased to 44.9). On this regimen, he had immune disease, or malignancy. 'irdly, there is a grading marked improvement in asthma symptoms and reduced size scale with points awarded for histopathology with dense of orbital pseudotumors. To continue to try to achieve corticosteroid sparing, he briefly used methotrexate and lymphoplasmacytic infiltrate and storiform fibrosis with or without obliterative phlebitis, positive immunostaining, then added hydroxychloroquine as an adjunctive treatment serum IgG4 >5x the upper limit of normal, having a set of with no further change in tumor size, so he was unwilling to glands involved, and having pulmonary or pancreas find- continue them. Pneumovax booster and one Prevnar booster ings, kidney findings, and retroperitoneal findings [19]. In dose were administered while the patient was off immu- 10–20% of cases, antinuclear antibodies (ANAs) are also nosuppression. An additional Prevnar booster was given positive [4]. Cases of IgG4-RD have been described with while he was on low-dose prednisone. He had an increase in elevated or normal levels of IgM, but low IgM and low pneumococcal protective antibodies from 3 of 14 to 4 of 14 functional antibodies have not previously been reported. during treatment. When the larger right orbital pseudotu- mor had regressed, the patient preferred to stop taking the prednisone and declined treatment for a period of 18 2. Case Presentation months. During this time, his bilateral eye lesions returned 'e patient was a 66-year-old Caucasian male with class III to near baseline size before treatment. Laboratory studies at this time showed an eosinophil count of 1096 (normal obesity (BMI 42) and a history of adult-onset asthma and allergies referred by his ophthalmologist for bilateral or- <500), SPEP with increased protein, decreased IgM at 20 mg/dl (normal >48 mg/dl), IgG 3570 mg/dl (normal bital masses that showed IgG4 lymphoproliferative disease on biopsy. On the right side, the medial superior orbital <1618 mg/dl), IgG4 1594 mg/dl (normal <86 mg/dl), IgG4/ IgG ratio of 0.45, ESR of 104 mm/h (normal<20 mm/h), and mass was approximately 1.0 cm × 1.3 cm and left-sided mass was 4 mm × 4 mm. A biopsy of both right and left elevated CRP at 9.9 mg/dl (normal<8.0 mg/dl) (See Table 1). 'e patient also began to report increased shortness of eyelid lesions including the bone and inferior orbital fat breath, and chest X-ray showed large left pleural effusion pad showed polyclonal lymphocytic infiltration and in- (Figure 1). 'oracentesis yielded 2 L of fluid from the left creased IgG4 plasma cells up to 98/HPF. 'e majority were lung that was negative for malignant cells but showed the T cells with a nonspecific mild increase in CD4:CD8 ratio and normal antigen expression. B cells were polyclonal with presence of reactive mesothelial cells and histiocytes. He saw cardiology and had workup for pleural effusion including normal antigen expression. 'ere was no immunophe- notypic evidence of non-Hodgkin lymphoma. 'e diag- neoplastic and infectious causes. 'e patient was unwilling to take corticosteroids again nosis of IgG4 lymphoproliferative disease was given based on elevated IgG4 levels and pathologic findings, and he was because of the efforts he had made to lose weight. He was willing to try azathioprine. He had a recurrence of left- referred to rheumatology. Systemic review was positive for fatigue, easy bruising and bleeding, cough, shortness of air, sided pleural effusion, and repeat thoracentesis showed similar findings. He underwent pleurodesis on the left wheezing, hypertension, joint pain, red dry eyes, and thorax. He was started on azathioprine 50 mg BID and postnasal drip. He did not smoke, denied recurrent in- fection other than rhinitis, and had no pertinent family corticosteroids, and during this period, the right orbital pseudotumor was at its smallest appearance. At this time, history. CT of the chest showed no evidence of pulmonary pa- the patient was following with oncology and the CT/PET scan showed 3.3 cm × 1.9 cm mass in his pelvis near the left renchymal fibrosis or interstitial lung disease. Laboratory investigations at the initial visit showed elevated IgG with seminal vesicle as well as incidental liver lesion without PET scan uptake. Biopsy of the pelvic mass showed IgG4 extremely elevated IgG4, decreased functional antibodies, and low IgM. Total IgG 1905 mg/dl (694–1618 mg/dl), IgG1 stain strongly positive. Oncology started prednisone 80 mg daily with taper, and the size of the pelvic mass decreased in 1106 mg/dl (382–929 mg/dl), IgG2 598 mg/dl (241–700 mg/ dl), IgG3 98 mg/dl (22–178 mg/dl), and IgG4 412 mg/dl size to 2.1 cm × 1.1 cm. 'e patient continues to undergo ongoing treatment with intermittent steroids and azathi- (4–86 mg/dl). 'is gives an IgG4/IgG ratio of .216 which oprine. Current pneumococcal antibody levels after a total correlates with values ≥0.2 in patients with IgG4-RD. IgA was normal at 222, and IgM was 40. His initial pneumo- of two Prevnar and two Pneumovax booster doses are 7 out of 14 protective. coccal vaccination was in three years prior to presentation. Case Reports in Immunology 3 Table 1: Laboratory values at presentation, several months into treatment while on corticosteroids and mycophenolate mofetil, and during relapse. IgG total IgG4 IgM ESR CRP Pneumococcal Haemophilus Platelets Eosinophils (nl 694–1618 mg/ (nl 4–86 mg/ (nl >48 mg/ (nl <20 mm/ (nl <8 mg/ antibodies antibodies (nl (nl 15–500) dl) dl) dl) hr) dl) (nl >8/14) (nl >1) 150–450) Presentation 1905 412 44 19 0.25 2/14 0.26 258 17 During 1760 377 43 11 1.09 3/14 0.34 240 432 treatment Relapse 3570 1594 20 104 9.3 4/14 0.17 250 1096 Figure 1: Lateral and posterior-anterior chest X-ray showing left-sided pleural effusion (arrows) during symptom relapse. for development of IgG4-RD including HLA-DRB1 and FC- 3. Discussion y [27]. Serological findings in IgG4-RD are nonspecific but 'is patient presented with hyper IgG4-related orbital can include elevations in erythrocyte sedimentation rate pseudotumors but, over time, developed recurrent pleural (ESR) and CRP, as well as positive ANA in 50% of patients effusions and a pelvic pseudotumor with notable laboratory and elevated RF in 20% [28]. Eosinophilia with increased IgE findings including low IgM and low functional protective has been found in 30–50% of IgG4-RD lesions, and an antibodies. eosinophilic predominance can be seen in orbital or upper 'e IgG4 subclass accounts for only 3–6% of the total respiratory tract disease [1, 21]. Typical serum protein IgG fraction, and up to 5% of the normal healthy population electrophoresis shows polyclonal hypergammaglobulinemia may have elevated IgG4 levels [3, 6, 19, 20]. IgG4 has been with beta-gamma bridging [5]. Serum IgG4 levels above linked to several diseases that are clinically separate from 1.35 g/dl may indicate higher risk for type 1 AIP and IgG4- IgG4-RD including pemphigus vulgaris, membranous glo- related sclerosing cholangitis and can be used to differentiate merulonephritis, rheumatoid arthritis, Castleman syn- pancreatic cancer from sclerosing cholangitis [20, 29, 30]. It drome, Wegener granulomatosis, pulmonary abscess, and may be useful to monitor serial IgG4 levels or circulating thrombotic thrombocytopenic purpura [1, 21–23]. In IgG4- plasmablasts to guide treatment, but evidence is still unclear related disease, the hallmark is a lymphoplasmacytic infil- [1, 11, 31]. Two histological findings are needed for diagnosis trate mainly consisting of IgG4+ plasma cells along with including whorly storiform fibrosis, obliterative phlebitis, characteristic histological findings. 'e role of IgG4 plasma dense lymphoplasmacytic infiltrate with many IgG4+ cells is not clearly understood as studies have not provided plasma cells, and eosinophilic infiltrate or granuloma for- insight into this process. CD19, CD27, and CD38+ plasma mation [1, 6, 17, 23]. blasts, as well as clonally expanded CD4+ and CD8+ cy- In IgG4-related disease, IgM, IgA, and other IgG sub- totoxic T lymphocytes, have been found to be elevated in the classes are frequently elevated [1]. In contrast to the current blood and in fibrotic lesions of patients with IgG4-RD literature, our patient presented with persistently suppressed [2, 24, 25]. One study showed a significant presence of M2 IgM levels and low protective antibody levels. In healthy macrophages among collagen fibers in fibrotic areas [26]. individuals, IgM autoantibodies play an important role in Cytokines thought to be involved in this process include IL- modulating immune responses and clearing self-antigens 13 and TGF-B in fibroblast activation, as well as IL-4 and IL- [32–34]. IgM deficiency typically presents with repeated 10 in class switching of IgG to IgG4 [2]. A Japanese study has infections but may also have an increased rate of allergic and identified several loci that indicated increased susceptibility autoimmune disease than the general population [32, 34]. 4 Case Reports in Immunology pleural effusion has been reported in several case studies of Almost 40% of patients with IgM deficiency present with asthma and allergic rhinitis [32]. One study showed that IgG4-related disease, but it is much more commonly seen with other lung manifestations such as parenchymal or patients with IgM deficiency had a higher rate of pathogenic ANA and 14% developed autoimmune disease [35]. pleural lesions [8, 42]. Hashimoto’s thyroiditis, SLE, multiple myositis, myasthenia 'is case report highlights and demonstrates the relative gravis, and Addison’s disease have been linked to low IgM effectiveness of steroid-sparing medications in IgG4-RD levels [32, 36]. Although this patient did not have significant treatment, and shows a rare presentation of IgG4-RD with sinopulmonary infections, he may have been at risk for low IgM levels and low functional antibodies. autoimmune disease related to immune deficiency. In IgM deficiency, cases of IgG subclass deficiency have been re- Data Availability ported, but hyper IgG4 disease has been reported only in one No data were used to support this study other than patient previous case report [34, 36, 37]. Immune response to medical record. vaccination has not been mentioned in IgG4-related disease. Some patients with selective IgM deficiency or IgG subclass Consent deficiency have been shown to have impaired IgG responses to the pneumococcal polysaccharide vaccines which may Written informed consent was obtained from the patient to improve with immunoglobulin therapy [34, 38]. At pre- publish this case report and any accompanying images. sentation, this patient was positive for only 3 of 14 protective pneumococcal antibodies as well as low haemophilus pro- Conflicts of Interest tective antibodies. His response to Pneumovax was poor. Repeated pneumococcal vaccines both Pneumovax and 'e authors declare no conflicts of interest regarding the Prevnar were required to maintain his protective antibodies, publication of this article. and overall, he had a much weaker than expected poly- saccharide response, only increasing from 3 to 4 protective References antibodies after vaccination. Treatment of IgG4-RD typically consists of prednisolone [1] E. Della-Torre, M. Lanzillotta, and C. Doglioni, “Immunology 0.6 mg/kg/d with gradual taper over a period of 3–6 months of IgG4-related disease,” Clinical & Experimental Immunol- [39]. Patients with elevated IgG4 at baseline, multiorgan ogy, vol. 181, no. 2, pp. 191–206, 2015. [2] D. Michailidou and P. Cohen, IgG4-Related Kidney Disease: involvement, and history of disease relapse may have a Diagnostics, Manifestations & More, 'e Rheumatologist, higher tendency to relapse after steroids have been dis- vol. 12, no. 5, pp. 17–20, 2018. continued. As a result, glucocorticoid sparing treatments [3] J. H. Ryu, H. Sekiguchi, and E. S. Yi, “Pulmonary manifes- have been used including azathioprine, mycophenolate tations of immunoglobulin G4-related sclerosing disease,” mofetil, methotrexate, cyclophosphamide, and tacrolimus, European Respiratory Journal, vol. 39, no. 1, pp. 180–186, but studies have not been conducted to compare efficacies of these agents [39]. Glucocorticoids with immunosuppres- [4] G. H. Neild, M. Rodriguez-Justo, C. Wall, and J. O. Connolly, sants have been shown to have a higher relapse-free rate than “Hyper-IgG4 disease: report and characterisation of a new glucocorticoids alone [16]. In patients with refractory dis- disease,” BMC Medicine, vol. 4, no. 1, p. 23, 2006. ease, rituximab can decrease serum IgG4 subclass concen- [5] L. Y. C. Chen, A. Mattman, M. A. Seidman, and M. N. Carruthers, “IgG4-related disease: what a hematologist trations. Early treatment is more likely to improve disease needs to know,” Haematologica, vol. 104, no. 3, pp. 444–455, manifestations in patients with prominent lymphoplasma- cytic infiltrate and especially in glandular tissues [1, 40]. [6] Y. Zen, S. Kitagawa, H. Minato et al., “IgG4-positive plasma When disease progresses to tightly organized collagen cells in inflammatory pseudotumor (plasma cell granuloma) bundles, definitive treatment is less successful, but potential of the lung,” Human Pathology, vol. 36, no. 7, pp. 710–717, to reverse collagen formation is still present. In this patient, the smallest tumor size was achieved with glucocorticoid [7] D. C. Trampert, L. M. Hubers, S. F. J. van de Graaf, and taper. Glucocorticoids also caused weight gain, so the patient U. Beuers, “On the role of IgG4 in inflammatory conditions: was reluctant to restart them after losing weight, so several lessons for IgG4-related disease,” Biochimica et Biophysica glucocorticoid-sparing treatments were tried in conjunction, Acta (BBA) - Molecular Basis of Disease, vol. 1864, no. 4, with the most symptom improvement during treatment with pp. 1401–1409, 2018. [8] S. N. Campbell, E. Rubio, and A. L. Loschner, “Clinical review mycophenolate mofetil and azathioprine. His case was of pulmonary manifestations of IgG4-related disease,” Annals complicated by poor adherence to treatment due to medi- of the American /oracic Society, vol. 11, no. 9, pp. 1466–1475, cation side effects and lack of concern on his part once the orbital lesions decreased in size. [9] M. Takahira, M. Kawano, Y. Zen, H. Minato, K. Yamada, and Several case studies have described incidence of immune K. Sugiyama, “IgG4-Related chronic sclerosing dacryoade- thrombocytopenia in patients with IgG4 disease. 'e inci- nitis,” Archives of Ophthalmology, vol. 125, no. 11, dence of this finding is unknown but has been postulated to pp. 1575–1578, 2007. be caused by antiplatelet antibodies or other IgG subclasses [10] M. Lanzillotta, C. Campochiaro, G. Mancuso et al., “Clinical of platelet antibody [41]. 'is patient had normal platelet phenotypes of IgG4-related disease reflect different prognostic levels throughout presentation and treatment. Isolated outcomes,” Rheumatology, vol. 59, no. 9, pp. 2435–2442, 2020. Case Reports in Immunology 5 [11] H. Pieringer, I. Parzer, A. Wohrer, ¨ P. Reis, B. Oppl, and [28] S. Nambiar and T. I. Oliver, IgG4 Related DiseaseStatPearls J. Zwerina, “IgG4- related disease: an orphan disease with Publishing, 2021, https://www.ncbi.nlm.nih.gov/books/ NBK499825/. many faces,” Orphanet Journal of Rare Diseases, vol. 9, no. 1, [29] M. Ebbo, A. Grados, E. Bernit et al., “Pathologies associated p. 110, 2014. with serum IgG4 elevation,” /e Internet Journal of Rheu- [12] H. Yamamoto, M. Yasuo, Y. Nomura et al., “IgG4-related matology, vol. 2012, Article ID 602809, 2012. airway involvement which developed in a patient receiving [30] T. Saeki, A. Saito, H. Yamazaki et al., “Tubulointerstitial corticosteroid therapy for autoimmune pancreatitis,” Internal nephritis associated with IgG4-related systemic disease,” Medicine, vol. 50, no. 24, pp. 3023–3026, 2011. Clinical and Experimental Nephrology, vol. 11, no. 2, [13] K. Tsushima, T. Tanabe, H. Yamamoto et al., “Pulmonary pp. 168–173, 2007. involvement of autoimmune pancreatitis,” European Journal [31] M. N. Carruthers, A. Khosroshahi, T. Augustin, of Clinical Investigation, vol. 39, no. 8, pp. 714–722, 2009. V. Deshpande, and J. H. Stone, “'e diagnostic utility of [14] T. Kamisawa, H. Nakajima, N. Egawa, N. Funata, K. Tsuruta, serum IgG4 concentrations in IgG4-related disease,” Annals and A. Okamoto, “IgG4-related sclerosing disease incorpo- of the Rheumatic Diseases, vol. 74, no. 1, pp. 14–18, 2015. rating sclerosing pancreatitis, cholangitis, sialadenitis and [32] S. Gupta and A. Gupta, “Selective IgM deficiency-an retroperitoneal fibrosis with lymphadenopathy,” Pancreatol- underestimated primary immunodeficiency,” Frontiers in ogy, vol. 6, no. 1-2, pp. 132–137, 2006. Immunology, vol. 8, p. 1056, 2017. [15] A. Shenoy, N. Mohandas, and A. Gottlieb, “Cutaneous and [33] C. Campochiaro, S. Atay, K. E. N. Clark, V. Ong, and systemic IgG4-related disease: a review for dermatologists,” C. P. Denton, “Autoimmunity and immunodeficiency at the Dermatology Online Journal, vol. 25, no. 6, https:// crossroad: autoimmune disorders as the presenting feature of escholarship.org/uc/item/9w91m8dz, 2019. selective IgM deficiency,” BMJ Case Reports, vol. 12, no. 1, [16] Z. Zhao, D. Mou, Z. Wang et al., “Clinical features and relapse Article ID e223180, 2019. risks of IgG4-related ophthalmic disease: a single-center ex- [34] A. G. Louis and S. Gupta, “Primary selective IgM deficiency: perience in China,” Arthritis Research & /erapy, vol. 23, an ignored immunodeficiency,” Clinical Reviews in Allergy & no. 1, p. 98, 2021. Immunology, vol. 46, no. 2, pp. 104–111, 2014. [17] T. Kubota and S. Moritani, “Orbital IgG4-related disease: [35] T. T. T. Nguyen and N. Baumgarth, “Natural IgM and the clinical features and diagnosis,” ISRN Rheumatology, development of B cell-mediated autoimmune diseases,” vol. 2012, Article ID 412896, 5 pages, 2012. Critical Reviews in Immunology, vol. 36, no. 2, pp. 163–177, [18] J. A. Plaza, J. A. Garrity, A. Dogan, A. Ananthamurthy, T. E. Witzig, and D. R. Salomão, “Orbital inflammation with [36] G. Ideura, K. Agematsu, Y. Komatsu et al., “Selective IgM IgG4-positive plasma cells,” Archives of Ophthalmology, deficiency accompanied with IgG4 deficiency, dermal com- vol. 129, no. 4, pp. 421–428, 2011. plications and a bronchial polyp,” Allergology International, [19] Z. S. Wallace, R. P. Naden, S. Chari et al., “American college of vol. 57, no. 1, pp. 99–105, 2008. rheumatology/European league against rheumatism IgG4- [37] V. Y. Y. Xu, M. Bell, A. Zahirieh et al., “A challenging di- related disease classification criteria working group. 'e 2019 agnosis of IgG4-related disease when understanding limita- American college of rheumatology/European league against tions of laboratory testing was pivotal,” Case reports in rheumatism classification criteria for IgG4-related disease,” medicine, vol. 2017, Article ID 8748696, 5 pages, 2017. Arthritis & Rheumatism, vol. 72, no. 1, pp. 7–19, 2020. [38] A. R. Parker, M. Skold, S. Harding, J. C. Barton, L. F. Bertoli, [20] H. Hamano, S. Kawa, A. Horiuchi et al., “High serum IgG4 and J. C. Barton, “Pneumococcal vaccination responses in concentrations in patients with sclerosing pancreatitis,” New adults with subnormal IgG subclass concentrations,” BMC England Journal of Medicine, vol. 344, no. 10, pp. 732–738, Immunology, vol. 20, no. 1, p. 29, 2019. [39] P. Brito-Zeron, ´ B. Kostov, X. Bosch, N. Acar-Denizli, [21] J. H. Stone, Y. Zen, and V. Deshpande, “IgG4-related disease,” M. Ramos-Casals, and J. H. Stone, “'erapeutic approach to IgG4-related disease,” Medicine, vol. 95, no. 26, Article ID New England Journal of Medicine, vol. 366, no. 6, pp. 539–551, e4002, 2016. [40] Y. Shimizu, M. Yamamoto, Y. Naishiro et al., “Necessity of [22] D. Inoue, Y. Zen, H. Abo et al., “Immunoglobulin G4-related early intervention for IgG4-related disease--delayed treatment lung disease: CT findings with pathologic correlations,” Ra- induces fibrosis progression,” Rheumatology, vol. 52, no. 4, diology, vol. 251, no. 1, pp. 260–270, 2009. pp. 679–683, 2013. [23] V. Deshpande, Y. Zen, J. K. Chan et al., “Consensus statement [41] S. Li, C. Deng, J. Chen, and F. Li, Mikulicz’s Disease with on the pathology of IgG4-related disease,” Modern Pathology, Immune /rombocytopenia: A New Immunoglobulin G4- vol. 25, no. 9, pp. 1181–1192, 2012. Mediated Disorder and Literature Review (NEEDS Format- [24] T. Kamisawa, N. Funata, Y. Hayashi et al., “A new clinico- ting) Department of Rheumatology and Immunology, Central pathological entity of IgG4-related autoimmune disease,” South University, Changsha, China, 2018. Journal of Gastroenterology, vol. 38, no. 10, pp. 982–984, 2003. [42] J. H. Choi, J. K. Sim, J. Y. Oh et al., “A case of IgG4-related [25] J. Backhus, C. Neumann, L. Perkhofer et al., “A follow-up disease presenting as massive pleural effusion and throm- study of a European IgG4-related disease cohort treated with bophlebitis,” Tuberculosis and Respiratory Diseases, vol. 76, Rituximab,” Journal of Clinical Medicine, vol. 10, no. 6, no. 4, pp. 179–183, 2014. p. 1329, 2021. [26] K. Miyabe, Y. Zen, L. D. Cornell et al., “Gastrointestinal and extra-intestinal manifestations of IgG4-related disease,” Gastroenterology, vol. 155, no. 4, pp. 990–1003, 2018. [27] M. Lanzillotta, G. Mancuso, and E. Della-Torre, “Advances in the diagnosis and management of IgG4 related disease,” BMJ, vol. 369, p. m1067, 2020. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Immunology Hindawi Publishing Corporation

Hyper IgG4-Related Disease Presenting with Orbital Tumor and Immune Deficiency

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Hindawi Case Reports in Immunology Volume 2021, Article ID 9260051, 5 pages https://doi.org/10.1155/2021/9260051 Case Report Hyper IgG4-Related Disease Presenting with Orbital Tumor and Immune Deficiency 1 2 Caroline G. Olson and Nancy Y. Olson University of Missouri-Kansas City, School of Medicine, Kansas City, MO, USA Allergy and Rheumatology Clinic of Kansas City, Overland Park, KS, USA Correspondence should be addressed to Caroline G. Olson; carolinegolson@gmail.com Received 2 July 2021; Accepted 2 September 2021; Published 20 September 2021 Academic Editor: Ahmad Mansour Copyright © 2021 Caroline G. Olson and Nancy Y. Olson. 'is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We report a case of IgG4-RD in a patient with high IgG4 levels, low functional antibodies, and low IgM levels. He presented with bilateral orbital pseudotumors and, after initial improvement on corticosteroids, relapsed with recurrent pleural effusion and pelvic pseudotumor. He had a grossly elevated serum IgG (1905 mg/dl) with elevations in all IgG subclasses but marked elevation in IgG4 (412 mg/dl), low IgM, and low pneumococcal antibodies. Orbital mass biopsy showed polyclonal lymphocytic infiltration and increased IgG4 plasma cells. 'e patient was started on prednisone and tried several immunosuppressive medications including mycophenolate mofetil, methotrexate, hydroxychloroquine, and azathioprine with decrease in size of the orbital pseudotumor. During a period when the patient stopped his medications, the pseudotumor enlarged with new development of recurrent pleural effusions. He was also found to have a pelvic mass that was biopsy positive for IgG4 proliferation. 'is case with progression to multiorgan involvement highlights the importance of identifying patients with IgG4-related disease. In contrast to previous cases with normal-to-high IgM, the IgM was low with impaired functional antibodies. and aortitis, head and neck limited, and systemic with 1. Introduction salivary or lacrimal gland swelling (Mikulicz disease) Immunoglobulin G4-related disease (IgG4-RD) is a rare [1, 8–10]. One study found that IgG4 played a role in all relapsing-remitting fibroinflammatory disease caused by archival cases of idiopathic retroperitoneal fibrosis analyzed monoclonal proliferation of IgG4+ plasma cells and dense [4]. Atypical presentations including tubulointerstitial ne- lymphoplasmacytic infiltration with reversible collagen phritis, glomerulonephritis, perineural disease, prostatitis, deposition [1–3]. It typically presents with insidious onset in orchitis, sclerosing mastitis, eosinophilic angiocentric fi- middle-aged to elderly men, although studies have shown brosis, interstitial lung disease, and pleural and pericardial higher IgG4 levels and worse disease in Asian populations effusions have been reported [1, 11, 12]. Intrathoracic in- [1, 3–5]. IgG4+ plasma cells produce antibodies that may volvement can include parenchymal opacities and interstitial lung disease, tracheobronchial stenosis, fibrosing media- regulate the immune system and protect against hyper- sensitivity anaphylaxis in patients with allergies [6, 7]. Pa- stinitis, nodular pleural lesions, and rarely, pleural effusion tients often have a longstanding history of allergic rhinitis, and may resemble sarcoidosis or lung cancer [3, 13]. Salivary bronchial asthma, or eczema at diagnosis. IgG4- RD can be and lacrimal gland involvement can cause facial and orbital asymptomatic or present with symptoms of mechanical swelling and can present similarly to Sjogren’s syndrome compression exerted by pseudotumor-like fibrotic masses. with sclerosing sialadenitis [1, 14]. Orbital pseudotumors 'e most common manifestations have been grouped into involve the lacrimal gland in 69% of cases but can also occur four clinical phenotypes including pancreatobiliary (type 1 in extraocular muscles, palpebrae, optic nerve, and orbital autoimmune pancreatitis (AIP)), retroperitoneal fibrosis bone, as well causing exophthalmos and restriction of ocular 2 Case Reports in Immunology movements [1, 15–17]. 'ese orbital manifestations tend to 'ree of 14 pneumococcal antibody titers were at a pro- have higher relapse rates on steroids and overall have higher tective level (>1.3 mcg/ml). Haemophilus influenza anti- bodies were decreased at 0.34. Angiotensin-converting cumulative doses of corticosteroids [10]. Several studies have shown a link between lacrimal gland involvement and de- enzyme (ACE) was low. Rheumatoid factor was positive at velopment of lymphoma [18]. 'e 2019 ACR/EULAR 28, and cyclic citrullinated peptide (CCP) was negative. standards for diagnosis of IgG4-RD are based on the 'e patient was started on prednisone 20 mg daily, and presence of characteristic clinical or radiological involve- to decrease steroid need with his weight, mycophenolate ment of a typical organ or pathological evidence of an in- mofetil 1000 mg BID was added. Mycophenolate was dis- flammatory lymphoplasmacytic infiltrate of uncertain continued due to side effects of dizziness and nausea. He was etiology. In addition, the patients must not have another dissatisfied with steroid weight gain at prednisone 20 mg explanation for their symptoms including infection, auto- daily (BMI had increased to 44.9). On this regimen, he had immune disease, or malignancy. 'irdly, there is a grading marked improvement in asthma symptoms and reduced size scale with points awarded for histopathology with dense of orbital pseudotumors. To continue to try to achieve corticosteroid sparing, he briefly used methotrexate and lymphoplasmacytic infiltrate and storiform fibrosis with or without obliterative phlebitis, positive immunostaining, then added hydroxychloroquine as an adjunctive treatment serum IgG4 >5x the upper limit of normal, having a set of with no further change in tumor size, so he was unwilling to glands involved, and having pulmonary or pancreas find- continue them. Pneumovax booster and one Prevnar booster ings, kidney findings, and retroperitoneal findings [19]. In dose were administered while the patient was off immu- 10–20% of cases, antinuclear antibodies (ANAs) are also nosuppression. An additional Prevnar booster was given positive [4]. Cases of IgG4-RD have been described with while he was on low-dose prednisone. He had an increase in elevated or normal levels of IgM, but low IgM and low pneumococcal protective antibodies from 3 of 14 to 4 of 14 functional antibodies have not previously been reported. during treatment. When the larger right orbital pseudotu- mor had regressed, the patient preferred to stop taking the prednisone and declined treatment for a period of 18 2. Case Presentation months. During this time, his bilateral eye lesions returned 'e patient was a 66-year-old Caucasian male with class III to near baseline size before treatment. Laboratory studies at this time showed an eosinophil count of 1096 (normal obesity (BMI 42) and a history of adult-onset asthma and allergies referred by his ophthalmologist for bilateral or- <500), SPEP with increased protein, decreased IgM at 20 mg/dl (normal >48 mg/dl), IgG 3570 mg/dl (normal bital masses that showed IgG4 lymphoproliferative disease on biopsy. On the right side, the medial superior orbital <1618 mg/dl), IgG4 1594 mg/dl (normal <86 mg/dl), IgG4/ IgG ratio of 0.45, ESR of 104 mm/h (normal<20 mm/h), and mass was approximately 1.0 cm × 1.3 cm and left-sided mass was 4 mm × 4 mm. A biopsy of both right and left elevated CRP at 9.9 mg/dl (normal<8.0 mg/dl) (See Table 1). 'e patient also began to report increased shortness of eyelid lesions including the bone and inferior orbital fat breath, and chest X-ray showed large left pleural effusion pad showed polyclonal lymphocytic infiltration and in- (Figure 1). 'oracentesis yielded 2 L of fluid from the left creased IgG4 plasma cells up to 98/HPF. 'e majority were lung that was negative for malignant cells but showed the T cells with a nonspecific mild increase in CD4:CD8 ratio and normal antigen expression. B cells were polyclonal with presence of reactive mesothelial cells and histiocytes. He saw cardiology and had workup for pleural effusion including normal antigen expression. 'ere was no immunophe- notypic evidence of non-Hodgkin lymphoma. 'e diag- neoplastic and infectious causes. 'e patient was unwilling to take corticosteroids again nosis of IgG4 lymphoproliferative disease was given based on elevated IgG4 levels and pathologic findings, and he was because of the efforts he had made to lose weight. He was willing to try azathioprine. He had a recurrence of left- referred to rheumatology. Systemic review was positive for fatigue, easy bruising and bleeding, cough, shortness of air, sided pleural effusion, and repeat thoracentesis showed similar findings. He underwent pleurodesis on the left wheezing, hypertension, joint pain, red dry eyes, and thorax. He was started on azathioprine 50 mg BID and postnasal drip. He did not smoke, denied recurrent in- fection other than rhinitis, and had no pertinent family corticosteroids, and during this period, the right orbital pseudotumor was at its smallest appearance. At this time, history. CT of the chest showed no evidence of pulmonary pa- the patient was following with oncology and the CT/PET scan showed 3.3 cm × 1.9 cm mass in his pelvis near the left renchymal fibrosis or interstitial lung disease. Laboratory investigations at the initial visit showed elevated IgG with seminal vesicle as well as incidental liver lesion without PET scan uptake. Biopsy of the pelvic mass showed IgG4 extremely elevated IgG4, decreased functional antibodies, and low IgM. Total IgG 1905 mg/dl (694–1618 mg/dl), IgG1 stain strongly positive. Oncology started prednisone 80 mg daily with taper, and the size of the pelvic mass decreased in 1106 mg/dl (382–929 mg/dl), IgG2 598 mg/dl (241–700 mg/ dl), IgG3 98 mg/dl (22–178 mg/dl), and IgG4 412 mg/dl size to 2.1 cm × 1.1 cm. 'e patient continues to undergo ongoing treatment with intermittent steroids and azathi- (4–86 mg/dl). 'is gives an IgG4/IgG ratio of .216 which oprine. Current pneumococcal antibody levels after a total correlates with values ≥0.2 in patients with IgG4-RD. IgA was normal at 222, and IgM was 40. His initial pneumo- of two Prevnar and two Pneumovax booster doses are 7 out of 14 protective. coccal vaccination was in three years prior to presentation. Case Reports in Immunology 3 Table 1: Laboratory values at presentation, several months into treatment while on corticosteroids and mycophenolate mofetil, and during relapse. IgG total IgG4 IgM ESR CRP Pneumococcal Haemophilus Platelets Eosinophils (nl 694–1618 mg/ (nl 4–86 mg/ (nl >48 mg/ (nl <20 mm/ (nl <8 mg/ antibodies antibodies (nl (nl 15–500) dl) dl) dl) hr) dl) (nl >8/14) (nl >1) 150–450) Presentation 1905 412 44 19 0.25 2/14 0.26 258 17 During 1760 377 43 11 1.09 3/14 0.34 240 432 treatment Relapse 3570 1594 20 104 9.3 4/14 0.17 250 1096 Figure 1: Lateral and posterior-anterior chest X-ray showing left-sided pleural effusion (arrows) during symptom relapse. for development of IgG4-RD including HLA-DRB1 and FC- 3. Discussion y [27]. Serological findings in IgG4-RD are nonspecific but 'is patient presented with hyper IgG4-related orbital can include elevations in erythrocyte sedimentation rate pseudotumors but, over time, developed recurrent pleural (ESR) and CRP, as well as positive ANA in 50% of patients effusions and a pelvic pseudotumor with notable laboratory and elevated RF in 20% [28]. Eosinophilia with increased IgE findings including low IgM and low functional protective has been found in 30–50% of IgG4-RD lesions, and an antibodies. eosinophilic predominance can be seen in orbital or upper 'e IgG4 subclass accounts for only 3–6% of the total respiratory tract disease [1, 21]. Typical serum protein IgG fraction, and up to 5% of the normal healthy population electrophoresis shows polyclonal hypergammaglobulinemia may have elevated IgG4 levels [3, 6, 19, 20]. IgG4 has been with beta-gamma bridging [5]. Serum IgG4 levels above linked to several diseases that are clinically separate from 1.35 g/dl may indicate higher risk for type 1 AIP and IgG4- IgG4-RD including pemphigus vulgaris, membranous glo- related sclerosing cholangitis and can be used to differentiate merulonephritis, rheumatoid arthritis, Castleman syn- pancreatic cancer from sclerosing cholangitis [20, 29, 30]. It drome, Wegener granulomatosis, pulmonary abscess, and may be useful to monitor serial IgG4 levels or circulating thrombotic thrombocytopenic purpura [1, 21–23]. In IgG4- plasmablasts to guide treatment, but evidence is still unclear related disease, the hallmark is a lymphoplasmacytic infil- [1, 11, 31]. Two histological findings are needed for diagnosis trate mainly consisting of IgG4+ plasma cells along with including whorly storiform fibrosis, obliterative phlebitis, characteristic histological findings. 'e role of IgG4 plasma dense lymphoplasmacytic infiltrate with many IgG4+ cells is not clearly understood as studies have not provided plasma cells, and eosinophilic infiltrate or granuloma for- insight into this process. CD19, CD27, and CD38+ plasma mation [1, 6, 17, 23]. blasts, as well as clonally expanded CD4+ and CD8+ cy- In IgG4-related disease, IgM, IgA, and other IgG sub- totoxic T lymphocytes, have been found to be elevated in the classes are frequently elevated [1]. In contrast to the current blood and in fibrotic lesions of patients with IgG4-RD literature, our patient presented with persistently suppressed [2, 24, 25]. One study showed a significant presence of M2 IgM levels and low protective antibody levels. In healthy macrophages among collagen fibers in fibrotic areas [26]. individuals, IgM autoantibodies play an important role in Cytokines thought to be involved in this process include IL- modulating immune responses and clearing self-antigens 13 and TGF-B in fibroblast activation, as well as IL-4 and IL- [32–34]. IgM deficiency typically presents with repeated 10 in class switching of IgG to IgG4 [2]. A Japanese study has infections but may also have an increased rate of allergic and identified several loci that indicated increased susceptibility autoimmune disease than the general population [32, 34]. 4 Case Reports in Immunology pleural effusion has been reported in several case studies of Almost 40% of patients with IgM deficiency present with asthma and allergic rhinitis [32]. One study showed that IgG4-related disease, but it is much more commonly seen with other lung manifestations such as parenchymal or patients with IgM deficiency had a higher rate of pathogenic ANA and 14% developed autoimmune disease [35]. pleural lesions [8, 42]. Hashimoto’s thyroiditis, SLE, multiple myositis, myasthenia 'is case report highlights and demonstrates the relative gravis, and Addison’s disease have been linked to low IgM effectiveness of steroid-sparing medications in IgG4-RD levels [32, 36]. Although this patient did not have significant treatment, and shows a rare presentation of IgG4-RD with sinopulmonary infections, he may have been at risk for low IgM levels and low functional antibodies. autoimmune disease related to immune deficiency. In IgM deficiency, cases of IgG subclass deficiency have been re- Data Availability ported, but hyper IgG4 disease has been reported only in one No data were used to support this study other than patient previous case report [34, 36, 37]. Immune response to medical record. vaccination has not been mentioned in IgG4-related disease. Some patients with selective IgM deficiency or IgG subclass Consent deficiency have been shown to have impaired IgG responses to the pneumococcal polysaccharide vaccines which may Written informed consent was obtained from the patient to improve with immunoglobulin therapy [34, 38]. At pre- publish this case report and any accompanying images. sentation, this patient was positive for only 3 of 14 protective pneumococcal antibodies as well as low haemophilus pro- Conflicts of Interest tective antibodies. His response to Pneumovax was poor. Repeated pneumococcal vaccines both Pneumovax and 'e authors declare no conflicts of interest regarding the Prevnar were required to maintain his protective antibodies, publication of this article. and overall, he had a much weaker than expected poly- saccharide response, only increasing from 3 to 4 protective References antibodies after vaccination. Treatment of IgG4-RD typically consists of prednisolone [1] E. Della-Torre, M. Lanzillotta, and C. Doglioni, “Immunology 0.6 mg/kg/d with gradual taper over a period of 3–6 months of IgG4-related disease,” Clinical & Experimental Immunol- [39]. Patients with elevated IgG4 at baseline, multiorgan ogy, vol. 181, no. 2, pp. 191–206, 2015. [2] D. Michailidou and P. Cohen, IgG4-Related Kidney Disease: involvement, and history of disease relapse may have a Diagnostics, Manifestations & More, 'e Rheumatologist, higher tendency to relapse after steroids have been dis- vol. 12, no. 5, pp. 17–20, 2018. continued. As a result, glucocorticoid sparing treatments [3] J. H. Ryu, H. Sekiguchi, and E. S. Yi, “Pulmonary manifes- have been used including azathioprine, mycophenolate tations of immunoglobulin G4-related sclerosing disease,” mofetil, methotrexate, cyclophosphamide, and tacrolimus, European Respiratory Journal, vol. 39, no. 1, pp. 180–186, but studies have not been conducted to compare efficacies of these agents [39]. Glucocorticoids with immunosuppres- [4] G. H. Neild, M. Rodriguez-Justo, C. Wall, and J. O. Connolly, sants have been shown to have a higher relapse-free rate than “Hyper-IgG4 disease: report and characterisation of a new glucocorticoids alone [16]. In patients with refractory dis- disease,” BMC Medicine, vol. 4, no. 1, p. 23, 2006. ease, rituximab can decrease serum IgG4 subclass concen- [5] L. Y. C. Chen, A. Mattman, M. A. Seidman, and M. N. Carruthers, “IgG4-related disease: what a hematologist trations. Early treatment is more likely to improve disease needs to know,” Haematologica, vol. 104, no. 3, pp. 444–455, manifestations in patients with prominent lymphoplasma- cytic infiltrate and especially in glandular tissues [1, 40]. [6] Y. Zen, S. Kitagawa, H. Minato et al., “IgG4-positive plasma When disease progresses to tightly organized collagen cells in inflammatory pseudotumor (plasma cell granuloma) bundles, definitive treatment is less successful, but potential of the lung,” Human Pathology, vol. 36, no. 7, pp. 710–717, to reverse collagen formation is still present. In this patient, the smallest tumor size was achieved with glucocorticoid [7] D. C. Trampert, L. M. Hubers, S. F. J. van de Graaf, and taper. Glucocorticoids also caused weight gain, so the patient U. Beuers, “On the role of IgG4 in inflammatory conditions: was reluctant to restart them after losing weight, so several lessons for IgG4-related disease,” Biochimica et Biophysica glucocorticoid-sparing treatments were tried in conjunction, Acta (BBA) - Molecular Basis of Disease, vol. 1864, no. 4, with the most symptom improvement during treatment with pp. 1401–1409, 2018. [8] S. N. Campbell, E. Rubio, and A. L. Loschner, “Clinical review mycophenolate mofetil and azathioprine. His case was of pulmonary manifestations of IgG4-related disease,” Annals complicated by poor adherence to treatment due to medi- of the American /oracic Society, vol. 11, no. 9, pp. 1466–1475, cation side effects and lack of concern on his part once the orbital lesions decreased in size. [9] M. Takahira, M. Kawano, Y. Zen, H. Minato, K. Yamada, and Several case studies have described incidence of immune K. Sugiyama, “IgG4-Related chronic sclerosing dacryoade- thrombocytopenia in patients with IgG4 disease. 'e inci- nitis,” Archives of Ophthalmology, vol. 125, no. 11, dence of this finding is unknown but has been postulated to pp. 1575–1578, 2007. be caused by antiplatelet antibodies or other IgG subclasses [10] M. Lanzillotta, C. Campochiaro, G. Mancuso et al., “Clinical of platelet antibody [41]. 'is patient had normal platelet phenotypes of IgG4-related disease reflect different prognostic levels throughout presentation and treatment. Isolated outcomes,” Rheumatology, vol. 59, no. 9, pp. 2435–2442, 2020. Case Reports in Immunology 5 [11] H. Pieringer, I. Parzer, A. Wohrer, ¨ P. Reis, B. Oppl, and [28] S. Nambiar and T. I. Oliver, IgG4 Related DiseaseStatPearls J. Zwerina, “IgG4- related disease: an orphan disease with Publishing, 2021, https://www.ncbi.nlm.nih.gov/books/ NBK499825/. many faces,” Orphanet Journal of Rare Diseases, vol. 9, no. 1, [29] M. Ebbo, A. Grados, E. Bernit et al., “Pathologies associated p. 110, 2014. with serum IgG4 elevation,” /e Internet Journal of Rheu- [12] H. Yamamoto, M. Yasuo, Y. Nomura et al., “IgG4-related matology, vol. 2012, Article ID 602809, 2012. airway involvement which developed in a patient receiving [30] T. Saeki, A. Saito, H. Yamazaki et al., “Tubulointerstitial corticosteroid therapy for autoimmune pancreatitis,” Internal nephritis associated with IgG4-related systemic disease,” Medicine, vol. 50, no. 24, pp. 3023–3026, 2011. Clinical and Experimental Nephrology, vol. 11, no. 2, [13] K. Tsushima, T. Tanabe, H. Yamamoto et al., “Pulmonary pp. 168–173, 2007. involvement of autoimmune pancreatitis,” European Journal [31] M. N. Carruthers, A. Khosroshahi, T. Augustin, of Clinical Investigation, vol. 39, no. 8, pp. 714–722, 2009. V. Deshpande, and J. H. Stone, “'e diagnostic utility of [14] T. Kamisawa, H. Nakajima, N. Egawa, N. Funata, K. Tsuruta, serum IgG4 concentrations in IgG4-related disease,” Annals and A. Okamoto, “IgG4-related sclerosing disease incorpo- of the Rheumatic Diseases, vol. 74, no. 1, pp. 14–18, 2015. rating sclerosing pancreatitis, cholangitis, sialadenitis and [32] S. Gupta and A. Gupta, “Selective IgM deficiency-an retroperitoneal fibrosis with lymphadenopathy,” Pancreatol- underestimated primary immunodeficiency,” Frontiers in ogy, vol. 6, no. 1-2, pp. 132–137, 2006. Immunology, vol. 8, p. 1056, 2017. [15] A. Shenoy, N. Mohandas, and A. Gottlieb, “Cutaneous and [33] C. Campochiaro, S. Atay, K. E. N. Clark, V. Ong, and systemic IgG4-related disease: a review for dermatologists,” C. P. Denton, “Autoimmunity and immunodeficiency at the Dermatology Online Journal, vol. 25, no. 6, https:// crossroad: autoimmune disorders as the presenting feature of escholarship.org/uc/item/9w91m8dz, 2019. selective IgM deficiency,” BMJ Case Reports, vol. 12, no. 1, [16] Z. Zhao, D. Mou, Z. Wang et al., “Clinical features and relapse Article ID e223180, 2019. risks of IgG4-related ophthalmic disease: a single-center ex- [34] A. G. Louis and S. Gupta, “Primary selective IgM deficiency: perience in China,” Arthritis Research & /erapy, vol. 23, an ignored immunodeficiency,” Clinical Reviews in Allergy & no. 1, p. 98, 2021. Immunology, vol. 46, no. 2, pp. 104–111, 2014. [17] T. Kubota and S. Moritani, “Orbital IgG4-related disease: [35] T. T. T. Nguyen and N. Baumgarth, “Natural IgM and the clinical features and diagnosis,” ISRN Rheumatology, development of B cell-mediated autoimmune diseases,” vol. 2012, Article ID 412896, 5 pages, 2012. Critical Reviews in Immunology, vol. 36, no. 2, pp. 163–177, [18] J. A. Plaza, J. A. Garrity, A. Dogan, A. Ananthamurthy, T. E. Witzig, and D. R. Salomão, “Orbital inflammation with [36] G. Ideura, K. Agematsu, Y. Komatsu et al., “Selective IgM IgG4-positive plasma cells,” Archives of Ophthalmology, deficiency accompanied with IgG4 deficiency, dermal com- vol. 129, no. 4, pp. 421–428, 2011. plications and a bronchial polyp,” Allergology International, [19] Z. S. Wallace, R. P. Naden, S. Chari et al., “American college of vol. 57, no. 1, pp. 99–105, 2008. rheumatology/European league against rheumatism IgG4- [37] V. Y. Y. Xu, M. Bell, A. Zahirieh et al., “A challenging di- related disease classification criteria working group. 'e 2019 agnosis of IgG4-related disease when understanding limita- American college of rheumatology/European league against tions of laboratory testing was pivotal,” Case reports in rheumatism classification criteria for IgG4-related disease,” medicine, vol. 2017, Article ID 8748696, 5 pages, 2017. Arthritis & Rheumatism, vol. 72, no. 1, pp. 7–19, 2020. [38] A. R. Parker, M. Skold, S. Harding, J. C. Barton, L. F. Bertoli, [20] H. Hamano, S. Kawa, A. Horiuchi et al., “High serum IgG4 and J. C. Barton, “Pneumococcal vaccination responses in concentrations in patients with sclerosing pancreatitis,” New adults with subnormal IgG subclass concentrations,” BMC England Journal of Medicine, vol. 344, no. 10, pp. 732–738, Immunology, vol. 20, no. 1, p. 29, 2019. [39] P. Brito-Zeron, ´ B. Kostov, X. Bosch, N. Acar-Denizli, [21] J. H. Stone, Y. Zen, and V. Deshpande, “IgG4-related disease,” M. Ramos-Casals, and J. H. Stone, “'erapeutic approach to IgG4-related disease,” Medicine, vol. 95, no. 26, Article ID New England Journal of Medicine, vol. 366, no. 6, pp. 539–551, e4002, 2016. [40] Y. Shimizu, M. Yamamoto, Y. Naishiro et al., “Necessity of [22] D. Inoue, Y. Zen, H. Abo et al., “Immunoglobulin G4-related early intervention for IgG4-related disease--delayed treatment lung disease: CT findings with pathologic correlations,” Ra- induces fibrosis progression,” Rheumatology, vol. 52, no. 4, diology, vol. 251, no. 1, pp. 260–270, 2009. pp. 679–683, 2013. [23] V. Deshpande, Y. Zen, J. K. Chan et al., “Consensus statement [41] S. Li, C. Deng, J. Chen, and F. Li, Mikulicz’s Disease with on the pathology of IgG4-related disease,” Modern Pathology, Immune /rombocytopenia: A New Immunoglobulin G4- vol. 25, no. 9, pp. 1181–1192, 2012. Mediated Disorder and Literature Review (NEEDS Format- [24] T. Kamisawa, N. Funata, Y. Hayashi et al., “A new clinico- ting) Department of Rheumatology and Immunology, Central pathological entity of IgG4-related autoimmune disease,” South University, Changsha, China, 2018. Journal of Gastroenterology, vol. 38, no. 10, pp. 982–984, 2003. [42] J. H. Choi, J. K. Sim, J. Y. Oh et al., “A case of IgG4-related [25] J. Backhus, C. Neumann, L. Perkhofer et al., “A follow-up disease presenting as massive pleural effusion and throm- study of a European IgG4-related disease cohort treated with bophlebitis,” Tuberculosis and Respiratory Diseases, vol. 76, Rituximab,” Journal of Clinical Medicine, vol. 10, no. 6, no. 4, pp. 179–183, 2014. p. 1329, 2021. [26] K. Miyabe, Y. Zen, L. D. Cornell et al., “Gastrointestinal and extra-intestinal manifestations of IgG4-related disease,” Gastroenterology, vol. 155, no. 4, pp. 990–1003, 2018. [27] M. Lanzillotta, G. Mancuso, and E. Della-Torre, “Advances in the diagnosis and management of IgG4 related disease,” BMJ, vol. 369, p. m1067, 2020.

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