Cutaneous light chain amyloidosis and erythema elevatum diutinum as the presenting features of IgA monoclonal gammopathy: a rare case report and comprehensive literature review

Cutaneous light chain amyloidosis and erythema elevatum diutinum as the presenting features of IgA monoclonal gammopathy: a rare case report and comprehensive literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Cutaneous light chain amyloidosis and erythema elevatum diutinum as the presenting features of IgA monoclonal gammopathy: a rare case report and comprehensive literature review Bing Han, Junfeng Zhou, Hesong Liu, Shanshan Li, Hong Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5785089/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Oct, 2025 Read the published version in Annals of Hematology → Version 1 posted 7 You are reading this latest preprint version Abstract Monoclonal gammopathy (MG) associated with dermatological disorders, which is classified as monoclonal gammopathy of clinical significance (MGCS), represents a well-established complication. These dermatologic conditions are linked to the infiltration and proliferation of malignant plasma cells or the deposition of monoclonal immunoglobulin in nonmalignant monoclonal gammopathy. Immunoglobulin light chain amyloidosis (AL amyloidosis) is a clonal, non-proliferative plasma cell disorder characterized by the deposition of fragments of immunoglobulin light chains in tissues. Erythema elevatum diutinum (EED) is clearly associated with monoclonal gammopathy, particularly IgA monoclonal gammopathy, although the pathomechanism has not been clearly established. In this article, we report an extremely rare case involving the coexistence of cutaneous light chain amyloidosis (AL amyloidosis) and erythema elevatum diutinum (EED) as the presenting features of IgA monoclonal gammopathy, which to our knowledge is the first reported case. During a 5-year follow-up period, intermittent occurrence of skin lesions persisted without significant changes observed in blood system examinations. Furthermore, we provided a comprehensive review of the existing literature on EED associated with IgA MG to enhance the understanding of skin significance of MG. Cutaneous AL amyloidosis Erythema elevatum diutinum IgA monoclonal gammopathy case report literature review Figures Figure 1 Figure 2 Figure 3 Introduction The monoclonal gammopathies encompass a spectrum of disorders characterized by the clonal proliferation of plasma cells or lymphoid cells, resulting in the secretion of a monoclonal protein (M-protein) [ 1 ]. These disorders exhibit clinical manifestations that range from asymptomatic to severe and potentially life-threatening disease. Typically, M-protein manifests as an intact immunoglobulin; however, it can also present as unbound light chains (free light chain, FLC) devoid of any heavy chain. These FLC can be detected in both blood and urine [ 1 ]. Severe manifestations can occur even with a small and quiescent clone due to the cytotoxicity of secreted M-protein, alteration of the host immune system, secretion of cytokines, and infiltration of plasma cells. The kidneys, peripheral nerves, and skin are among the primary organs that may be affected [ 2 ]. Therefore, dermatological manifestations associated with monoclonal gammopathies should be classified alongside monoclonal gammopathy of clinical significance (MGCS) as a well-recognized complication referred to as monoclonal gammopathy of skin significance [ 3 ]. Immunoglobulin light chain (AL) amyloidosis is characterized by clonal non-proliferative plasma cell disorder leading to deposition of immunoglobulin light chain fragments in tissues. Erythema elevatum diutinum (EED), which is strongly linked with monoclonal gammopathy, is more commonly observed in cases involving IgA monoclonal gammopathy; however, its precise pathomechanism remains unclear. Here we present an extremely rare case where coexistence of cutaneous AL amyloidosis and EED was identified as the primary clinical manifestation associated with IgA monoclonal gammopathy. To our knowledge, this represents the first reported instance highlighting cutaneous AL amyloidosis and EED as primary clinical presentations in association with IgA monoclonal gammopathy. Case report The patient, a 78-year-old male, presented with a six-year history of multiple ecchymoses, purple-red papules, nodules, and plaques distributed on his ears, trunk, limbs, hands, and feet. Mild continuous pruritus was reported but resolved spontaneously. He was misdiagnosed as erythema multiforme for a long time and received symptomatic treatment without improving. Additionally, he had developed blood blisters and ulcers on his feet over the past two weeks which caused significant pain. There was no family history of hematologic or autoimmune diseases. Physical examination revealed multiple purple-red papules, nodules, and plaques affecting his auricles, trunk, limbs including necks, hands, and feet (Fig. 1 ). Furthermore, the lateral margins of his right foot exhibited large ecchymoses accompanied by ulcers. Laboratory investigation revealed an elevated serum IgA level (6.19 g/L; reference range 0.7-4.0 g/L). Serum protein electrophoresis demonstrated increased levels of β-globulin (15%; reference range 7.0–11.0%) and γ-globulin (19.5%; reference range 9.0–18.0%). Additionally, serum immunofixation electrophoresis confirmed the presence of monoclonal IgA λ FLCs, while serum κ FLCs were measured at 24.00 mg/L (reference range 6.7-22.4mg/L) and serum λ FLCs were measured at 90.00 mg/L (reference range 8.3–27 mg/L), resulting in a κ/λ ratio of 0.26 (reference range: 0.26–1.65). Examination for early renal injury revealed a urine microalbumin level of 0.7mg/24h (reference value <0.4mg/24h), urine κ FLCs of 17.60mg/24h (reference value<14 .20mg/24h), and urine λ FLCs of 19 .5mg/24h (reference value<7 .80mg/24h) with a κ/λ ratio consistent with the reference range(κ/λ = 0.26). The urine immunofixation electrophoresis test produced negative findings. Normal results were obtained from additional laboratory tests, such as routine blood, urine, and stool examinations; clotting assessments; as well as liver and renal function evaluations. Measurements of 24-hour urinary protein excretion levels along with troponin I and proBNP concentrations fell within the normal range. Negative results were observed for hepatitis B virus markers, human immunodeficiency virus antigen/antibody testing, Treponema pallidum particle agglutination assay, antinuclear antibody screening, as well as tumor marker analysis. No abnormalities were detected in the electrocardiogram recordings or during the echocardiographic examination or imaging studies such as chest X-ray or abdominal color Doppler ultrasound. The bone marrow aspiration biopsy revealed the presence of rouleaux formations composed predominantly of mature erythrocytes with a proportionate representation of 2% proplasmacytes. Flow cytometry analysis of bone marrow revealed that abnormal monoclonal plasma cells accounted for 0.32% of the total number of nucleated bone marrow cells.The aberrant expression of CD38, CD138, CD200, CXCR4, and cIgλ was observed in these cells while the expression of CD34, CD117, CD19, CD20, CD7, CD5, CD33, CD10, CD56, CD13, CD22, CD27, CD28, and cIgκ was lost. The biopsy from the lateral margin of the foot lesion revealed eosinophilic amorphous material deposition within the dermis. This material exhibited positive Congo red staining and displayed apple-green birefringence under polarized light microscopy. Perivascular infiltrates consisting of lymphocytes, plasma cells, neutrophils, and eosinophils were observed in the dermis (Fig. 2 ). Immunohistochemical staining confirmed the presence of κ and λ chain-positive plasma cells consistent with AL amyloidosis. Furthermore, the biopsy from the lesion on the left arm demonstrated a perivascular infiltrate primarily composed of lymphocytes and neutrophils along with extravasation of red blood cells in the dermis. Fibrinoid necrosis of small vessels, leukocytoclasia and eosinophilic amorphous material around vessels were observed. This material exhibited positive Congo red staining and displayed apple-green birefringence under polarized light microscopy, indicating the presence of amyloidosis accompanied by leukocytoclastic vasculitis (Fig. 3 ). Immunohistochemical staining (IHC) of skin biopsies revealed positive expression of both κ and λ light chains, as well as scattered cells expressing κ and λ light chains in the dermis. In situ hybridization (ISH) results from skin biopsies showed scattered positivity for both κ and λ light chains without evidence of clonality. Based on physical examination, laboratory tests, and histopathological findings, the patient was diagnosed with IgA monoclonal gammopathy, cutaneous AL amyloidosis, and EED. Subsequently, the patient was transferred to the hemato-oncology department for further treatment. During a 5-year follow-up period, intermittent occurrence of skin lesions persisted without significant changes observed in blood system examinations. Symptomatic treatment (oral Dapsone) was provided while regular follow-up appointments were scheduled. Discussion Monoclonal gammopathy of clinical significance (MGCS) refers to non-malignant monoclonal gammopathies that result in substantial disease burden. As per the International Myeloma Working Group, MGCS is characterized by the presence of a monoclonal immunoglobulin or light chain, symptoms or clinical manifestations attributed to the presence of monoclonal protein, and not meeting diagnostic criteria for multiple myeloma or other lymphoplasmacytic disorders [ 4 ]. According to Daoud & al., monoclonal gammopathy of skin significance can be classified into four distinct groups along with MGCS [ 2 ]. Group 1 dermatosis results from infiltration, proliferation, and diffusion of malignant plasma cells in the skin, such as Waldenström's macroglobulinemia and myeloma, or from M-protein deposition, such as AL amyloidosis and cryoglobulinemia [ 2 ]. Group 2 dermatosis is closely associated with non-malignant monoclonal gammopathy where pathogenesis may arise from total or partial deposition of monoclonal immunoglobulins along with autoantibody activity and cytokine-mediated inflammation including scleromyxedema, pyoderma gangrenosum, acute febrile neutrophilic dermatosis (Sweet disease), or EED [ 2 ]. AL amyloidosis is characterized by the abnormal production of monoclonal κ and λ light chains, which serve as the substrate for amyloid fibril formation and subsequent deposition in various organs, resulting in organ damage and clinical manifestations [ 5 ]. The kidney, peripheral nerves, and skin are among the most commonly affected organs [ 6 ]. Dermatological manifestations of AL amyloidosis can vary widely, including purpura, papules, plaques, nodules, hemorrhagic or non-hemorrhagic bullae, subcutaneous nodules, alopecia and scleroderma-like changes. Oral involvement may encompass macroglossia, tongue induration, and gum bleeding. Nail dystrophy characterized by onychorrhexis, onychoschizia, and nail splitting is an exceedingly rare manifestation. Most of these cutaneous disorders are nonspecific; however, macroglossia and periorbital purpura represent specific clinical manifestations of AL amyloidosis. A tissue biopsy stained with Congo red that demonstrates apple-green birefringence in amyloid deposits is imperative for the diagnosis of AL amyloidosis. It is essential to confirm that the amyloid comprises immunoglobulin light chains. Laser capture mass spectroscopy is considered the gold standard for confirming the composition of the amyloid protein and distinguishing AL amyloidosis from other forms [ 7 ]. There are two subtypes of AL amyloidosis: AL-κ and more commonly, AL-λ. The higher prevalence of AL-λ likely reflects its propensity to form β-pleated sheets. Overall, both AL-κ and AL-λ exhibit common histopathologic changes [ 8 ]. Our patient presented with an IgA-λ monoclonal gammopathy associated with AL-λ subtype. However, potential differences in clinical manifestations, histologic findings, and clinical significance between the two subtypes of AL amyloidosis remain unclear. EED is a rare and chronic dermatosis characterized by leukocytoclastic vasculitis. The cutaneous manifestations of EED are typically described as erythematous to violaceous papules, plaques, or nodules [ 9 ]. It primarily affects the extensor surfaces of joints, axilla, posterior auricular area, buttocks, soles, larynx, and acral sites. Some patients with EED may experience non-cutaneous manifestations such as arthralgia, scleritis, panuveitis, ulcerative keratitis, and neuropathy [ 9 ]. EED is frequently observed in association with monoclonal gammopathy, particularly IgA monoclonal gammopathy or multiple myeloma. Additionally, it can be found in conjunction with numerous infectious and hematologic diseases, malignancies,and neutrophilic dermatoses as well as autoimmune and inflammatory diseases. Histopathologically, early lesions exhibit characteristic leukocytoclastic vasculitis with neutrophilic infiltrates surrounding blood vessels from the upper to mid-dermis, accompanied by eosinophils, lymphocytes, plasma cells, and nuclear debris. With disease progression, late-stage lesions demonstrate granulation tissue formation and storiform fibrosis. Additionally, focal areas of neutrophilic vasculitis may be observed. The etiology of EED remains poorly understood but is postulated to involve immune complex-mediated mechanisms that activate complement pathways, induce neutrophil infiltration and release of destructive enzymes, trigger IL-8 activation for selective recruitment of leukocytes to blood vessels resulting in subsequent leukocytoclastic vasculitis [ 10 ]. To investigate the association between EED and IgA monoclonal gammopathy as well as AL amyloidosis, we conducted a comprehensive search of case reports on the electronic PubMed database ( https://pubmed.ncbi.nlm.nih.gov/ ; up to December 2024) from 1992 to 2024 using the keywords "erythema elevatum diutinum (EED)" and "IgA monoclonal gammopathy (IgA paraproteinemia)". Our search identified a total of 19 cases reporting EED associated with IgA monoclonal gammopathy (Table 1 ) [ 11 – 24 ]. Additionally, seven of these patients presented with other complications or comorbidities, including pyoderma gangrenosum in three cases, Wegener granulomatosis in one case, Hepatitis C in one case, oropharyngeal ulceration in two cases, and Hashimoto's disease in one case. Among the 19 EED patients reported in the literature, serum immunofixed electrophoresis was performed for 14 individuals with IgA monoclonal gammopathy. Of these cases, nine showed κ light chain positivity while five exhibited λ light chain positivity. ANCA examination was conducted for five out of the 19 EED patients mentioned in the literature: three were ANCA positive and two were ANCA negative; notably, this particular patient was ANCA negative.The authors propose that further investigation is warranted to elucidate the role of ANCA in the pathogenesis of EED. To date, no documented instances have been reported regarding the coexistence of AL amyloidosis and EED in association with IgA monoclonal gammopathy. Table 1 Literature review of published cases of Erythema elevatum diutinum associated with IgA monoclonal gammopathy Case Author(date) Age(yr)/ sex Laboratory examination Accompany diseases Treatment Outcome 1 Yiannias JA et al [ 11 ] (1992) 35/UK Immunoelectrophoresis IgAκ(+) No No details No details 2 Yiannias JA et al [ 11 ] (1992) 37/UK Immunoelectrophoresis IgAκ(+) No No details No details 3 Wilkinson SM et al [ 12 ] (1992) 46/M Immunoelectrophoresis IgAκ(+) No Dapsone Improved 4 Wilkinson SM et al [ 12 ] (1992) 63/F Immunoelectrophoresis IgA λ(+) No Intralesional triamcinolone, dapsone, excision No effect No tolerated Improved 5 Wilkinson SM et al [ 12 ] (1992) 44/M Immunoelectrophoresis IgA λ(+) No Dapsone Improved 6 Wilkinson SM et al [ 12 ] (1992) 68/F Immunoelectrophoresis IgA λ(+) No Dapsone Improved 7 Gina M et al [ 13 ] (1993) 69/M Immunoelectrophoresis IgAκ(+), ANCA༈+༉ Wegener's granulomatosis Dapsone, methylprednisolonecy, clophosphamide Improved 8 Wayte JA et al [ 14 ] (1995) 27/M Immunoelectrophoresis IgAκ(+) Pyoderma gangrenosum Prednisolone, dapsone, minocycline Improved 9 Chow RK et al [ 15 ] (1996) 72/F IgA 8g/L (0.7–3.9 g/L) No Plasma exchange Improved 10 Chowdhury MM et al [ 16 ] (2002) 59/M Immunoelectrophoresis IgAκ(+) No Dapsone, MTX, sulfapyridine, nicotinamide and colchicine Progressed 11 Simpson R et al [ 17 ] (2010) 54/M ANCA(+) No No details No details 12 Simpson R et al [ 17 ] (2010) 60/M ANCA(+) Pyoderma gangrenosum No details No details 13 Thomas CL et al [ 18 ] (2015) 27/F Immunoelectrophoresis IgAκ(+) No Excision Healed 14 Manni E et al [ 19 ] (2015) 83/M IgA level 760 mg/dL ImmunoelectrophoresisIgAκ(+) No Plasma exchange, Thalidomide Improved 15 Patnala GP et al [ 20 ] (2016) 55/F Immunoelectrophoresis IgA λ(+) No Dapsone, doxycycline Improved 16 Bansal R et al [ 21 ] (2017) 50/M IgA 2290mg/dl Hepatitis C Dapsone Improved 17 Kentley J et al [ 22 ] (2017) 60/M Immunoelectrophoresis IgA λ(+) IgA 6.29(0.8-4) Oropharyngeal ulceration Colchicine, dapsone, hydroxychloroquine Improved 18 Hügel R et al [ 23 ] (2018) 37/F Immunoelectrophoresis IgAκ(+) Pyoderma gangrenosum, oropharyngeal ulceration Methylprednisolone, dapsone Improved 19 Jacob JS et al [ 24 ] (2021) 44/F Immunoelectrophoresis IgA(+) Hashimoto's disease Indomethacin, intralesional triamcinolone, dapsone, excision Improved F: Female; M: Male The primary objective of AL amyloidosis treatment is to promptly reduce the production of amyloidogenic light chains, prevent further deposition of amyloid protein in vital organs, and ameliorate or reverse progressive damage to affected organs. The main approach involves chemotherapy targeting the underlying clonal plasma cell dyscrasia. Approximately 5% of AL amyloidosis patients present with localized lesions in various sites, such as the bladder, throat, stomach, colon, skin, lungs, and urinary tract (as observed in our patient) [ 6 ]. These individuals typically do not develop systemic disease; therefore, observation of asymptomatic lesions or surgery and radiotherapy is preferred. Dapsone serves as the first-line treatment for EED due to its antimicrobial properties that impair neutrophil chemotaxis and function. Other therapeutic options include NSAIDs, niacinamide, tetracyclines, chloroquine, colchicine, and plasmapheresis [ 9 ]. Additionally,surgical excision may be considered if fibrotic nodules exhibit a poor response to dapsone and are limited in extent. Our patient has been regularly followed up for 5 years without evident systemic damage and with slow progression of lesions. Hence, current management involves only symptomatic treatment along with close monitoring. Conclusion We present a case involving an elderly male patient who endured misdiagnosis and inappropriate treatment for a duration of six years. Ultimately, through comprehensive laboratory evaluations and histopathological biopsies, he was diagnosed with IgA MG associated cutaneous AL amyloidosis combined with EED. We underscore the critica l role of skin pathology in diagnosing dermatological manifestations associated with MG. Additionally, we conduct a literature review on EED associated with IgA MG, highlighting the necessity for further research to clarify the involvement of ANCA in the pathogenesis of EED. Declarations Author Contributions Bing Han: Writing – review & editing, Writing – original draft, Software, Resources, Data curation. Junfeng Zhou: Investigation. Hesong Liu: Resources. Shanshan Li and Hong Wang: Supervision, Conceptualization, Writing – review & editing, Writing – original draft, Methodology, Formal analysis, Conceptualization. Hong Wang and Shanshan Li contributed equally to the work and should be regarded as co-corresponding authors. All authors take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Funding No funding or sponsorship was received for the publication of this study. Data availability No datasets were generated or analysed during the current study. Ethics approval Not applicable. Clinical Trial Registration Not applicable. Patient consent statement Written informed consent was obtained from the patient. Consent to publish The patient has consented to the submission of the case report to the journal. Permission to reproduce material from other sources Not applicable. Competing interests The authors have no competing interests as defined by Springer, or other interests that might be perceived to influence the results and/or discussion reported in this paper. References Claveau JS, Wetter DA, Kumar S (2022) Cutaneous manifestations of monoclonal gammopathy. Blood Cancer J 12(4):58. https://doi.org/10.1038/s41408-022-00661-1 Daoud MS, Lust JA, Kyle RA, Pittelkow MR (1999) Monoclonal gammopathies and associated skin disorders J Am Acad Dermatol 40(4):507–35. https://doi.org/10.1016/s0190-9622(99)70434-2 Fermand JP, Bridoux F, Dispenzieri A, Jaccard A, Kyle RA, Leung N, et al (2018) Monoclonal gammopathy of clinical significance: a novel concept with therapeutic implications Blood 132(14):1478-85. https://doi.org/10.1182/blood-2018-04-839480 Schmidt T, Callander N (2020) Diagnosis and Management of Monoclonal Gammopathy and Smoldering Multiple Myeloma. 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Am J Clin Pathol 160(2):144-9. https://doi.org/ 10.1093/ajcp/aqad017 Awan BE, Noda Y, Yabuno Y, Hokazono Y, Ansai S, Ogawa R (2021) A Case of Erythema Elevatum Diutinum (EED) Exhibiting A Keloid-Like Appearance. Dermatol Ther (Heidelb) 11(6):2235-40. https://doi: 10.1007/s13555-021-00639-0 Grabbe J, Haas N, Möller A, Henz BM (2000) Erythema elevatum diutinum--evidence for disease-dependent leucocyte alterations and response to dapsone. Br J Dermatol 43(2); 415-20. https://doi.org/10.1046/j.1365-2133.2000.03673.x Yiannias JA, el-Azhary RA, Gibson LE (1992) Erythema elevatum diutinum: a clinical and histopathologic study of 13 patients. J Am Acad Dermatol 26(1):38-44. https://doi.org/10.1016/0190-9622(92)70003-x Wilkinson SM, English JS, Smith NP, Wilson-Jones E, Winkelmann RK (1992) Erythema elevatum diutinum: a clinicopathological study. Clin Exp Dermatol 17(2):87-93. https://doi.org/10.1111/j.1365-2230.1992.tb00171.x Kavanagh GM, Colaco CB, Bradfield JW, Archer CB (1993) Erythema elevatum diutinum associated with Wegener's granulomatosis and IgA paraproteinemia. J Am Acad Dermatol 28(5):846-9. https://doi.org/ 10.1016/0190-9622(93)70115-a Wayte JA, Rogers S, Powell FC (1995) Pyoderma gangrenosum, erythema elevatum diutinum and IgA monoclonal gammopathy. Australas J Dermatol 36(1):21-23. https://doi.org/10.1111/j.1440-0960.1995.tb00919.x Chow RK, Benny WB, Coupe RL, Dodd WA, Ongley RC (1996) Erythema elevatum diutinum associated with IgA paraproteinemia successfully controlled with intermittent plasma exchange. Arch Dermatol 132(11):1360-4 Chowdhury MM, Inaloz HS, Motley RJ, Knight AG (2002) Erythema elevatum diutinum and IgA paraproteinaemia: 'a preclinical iceberg'. 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Indian Dermatol Online J 7(4):300-3. https://doi.org/ 10.4103/2229-5178.185472 Bansal R, Aron J, Rajnish I (2017) Erythema Elevatum Diutinum. Am J Med Sci 353(2):189. https://doi.org/10.1016/j.amjms.2016.05.005 Kentley J, Marshall C, Bewley A (2017) Erythema elevatum diutinum-associated with loss of the uvula. JAAD Case Rep 3(3):212-4. https://doi.org/10.1016/j.jdcr.2017.02.007 Hügel R, Brasch J, Yordanova I, Schröder JO, Fazel A, Gläser R, et al (2018) Erythema elevatum diutinum associated with severe oropharyngeal ulceration and pyoderma gangrenosum. J Dtsch Dermatol Ges 16(5):617-20. https://doi.org/10.1111/ddg.13508 Jacob JS, Tschen J (2021) Atypical Presentation of Erythema Elevatum Diutinum in a Patient With Hashimoto's Disease. Cureus 13(9):e18214. https://doi.org/10.7759/cureus.18214 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 20 Oct, 2025 Read the published version in Annals of Hematology → Version 1 posted Editorial decision: Accepted 04 Sep, 2025 Reviews received at journal 01 Sep, 2025 Reviewers agreed at journal 24 Aug, 2025 Reviewers agreed at journal 09 Apr, 2025 Reviewers invited by journal 28 Mar, 2025 Submission checks completed at journal 28 Mar, 2025 First submitted to journal 18 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5785089","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":435435662,"identity":"abe7b3b3-6c10-4d71-a7b4-ec93b01d4dde","order_by":0,"name":"Bing Han","email":"","orcid":"","institution":"1st hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Bing","middleName":"","lastName":"Han","suffix":""},{"id":435435663,"identity":"11792cd0-d9f7-467c-b5c0-220a2e2499e3","order_by":1,"name":"Junfeng Zhou","email":"","orcid":"","institution":"1st hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Junfeng","middleName":"","lastName":"Zhou","suffix":""},{"id":435435664,"identity":"070aa311-1c19-4fe6-a942-a2e60c318c81","order_by":2,"name":"Hesong Liu","email":"","orcid":"","institution":"1st hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Hesong","middleName":"","lastName":"Liu","suffix":""},{"id":435435665,"identity":"b0eafde4-24f9-4dcd-bee5-cb7cacd1040c","order_by":3,"name":"Shanshan Li","email":"","orcid":"","institution":"1st hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Shanshan","middleName":"","lastName":"Li","suffix":""},{"id":435435666,"identity":"f78b4aa6-4ccf-447a-b247-37b699918e55","order_by":4,"name":"Hong Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYFACHhBhw8wHZxOpJY2ZjVQthxmI12JwgPfg44Jf59nZJBIYH7xtY5A3J6yFL9l4Zt9tZqAWZsO5bQyGOxsIaDE7wGMmzdsD1sImzdvGkGBwgDgt50Ba2H8Tr4XnxwGwLcxEabE/wGNszNuQzMzG87BZcs45CcMNhLRINvAYPub5Y5fMz5588MObMht5grYwyD9gYGBsY0gGkg1ArgQh9TDwh8GOWKWjYBSMglEwAgEANu00ql6QvbAAAAAASUVORK5CYII=","orcid":"","institution":"1st hospital of Jilin University","correspondingAuthor":true,"prefix":"","firstName":"Hong","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2025-01-08 02:53:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5785089/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5785089/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00277-025-06621-6","type":"published","date":"2025-10-20T16:16:35+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79613877,"identity":"97dd4f6b-97fa-43b7-8bf0-be99b0b22875","added_by":"auto","created_at":"2025-03-31 18:41:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":40639270,"visible":true,"origin":"","legend":"\u003cp\u003eClinical presentation of the lesions. Multiple purple-red papules, nodules, and plaques, located on his auricles (a), trunk (b), limbs (c) including necks, hands, and feet.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5785089/v1/c56c024d665c2dcc5f302588.png"},{"id":79613888,"identity":"fc65d8e4-49f8-4a33-a70c-8e1e6eba9aa3","added_by":"auto","created_at":"2025-03-31 18:41:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":165518715,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathology of the ateral margin of the foot lesion. a, b Perivascular infiltration composed of lymphocytes，plasma cells，neutrophils，and eosinophils, eosinophilic amorphous material deposition within the dermis. (a,×40, hematoxylin and eosin [H\u0026amp;E]; b, ×200, H\u0026amp;E)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5785089/v1/26a41c66a70ba2f8ababe996.png"},{"id":79614917,"identity":"caabd26e-ce40-4b64-a22d-5c7f85ac0c8c","added_by":"auto","created_at":"2025-03-31 18:57:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":23945065,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathology of the lesion on the left arm. a, b Perivascular infiltration primarily composed of lymphocytes and neutrophils along with extravasation of red blood cells in the dermis. Fibrinoid necrosis of small vessels, leukocytoclasia and eosinophilic amorphous material around vessels were observed. (a, ×40, H\u0026amp;E; b, ×200, H\u0026amp;E). c, d This material exhibited positive Congo red staining and displayed apple-green birefringence under polarized light microscopy. (c, ×200, Congo red staining; d, ×200, polarized light microscopy).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5785089/v1/417e34d2dc7449c76e014230.png"},{"id":94505692,"identity":"602092a7-ff8f-4983-90eb-3fd5b7d444c6","added_by":"auto","created_at":"2025-10-28 16:20:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":135982568,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5785089/v1/c3c97917-bd6a-4faf-a0ef-9d212c513630.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cutaneous light chain amyloidosis and erythema elevatum diutinum as the presenting features of IgA monoclonal gammopathy: a rare case report and comprehensive literature review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe monoclonal gammopathies encompass a spectrum of disorders characterized by the clonal proliferation of plasma cells or lymphoid cells, resulting in the secretion of a monoclonal protein (M-protein) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. These disorders exhibit clinical manifestations that range from asymptomatic to severe and potentially life-threatening disease. Typically, M-protein manifests as an intact immunoglobulin; however, it can also present as unbound light chains (free light chain, FLC) devoid of any heavy chain. These FLC can be detected in both blood and urine [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Severe manifestations can occur even with a small and quiescent clone due to the cytotoxicity of secreted M-protein, alteration of the host immune system, secretion of cytokines, and infiltration of plasma cells. The kidneys, peripheral nerves, and skin are among the primary organs that may be affected [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Therefore, dermatological manifestations associated with monoclonal gammopathies should be classified alongside monoclonal gammopathy of clinical significance (MGCS) as a well-recognized complication referred to as monoclonal gammopathy of skin significance [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Immunoglobulin light chain (AL) amyloidosis is characterized by clonal non-proliferative plasma cell disorder leading to deposition of immunoglobulin light chain fragments in tissues. Erythema elevatum diutinum (EED), which is strongly linked with monoclonal gammopathy, is more commonly observed in cases involving IgA monoclonal gammopathy; however, its precise pathomechanism remains unclear. Here we present an extremely rare case where coexistence of cutaneous AL amyloidosis and EED was identified as the primary clinical manifestation associated with IgA monoclonal gammopathy. To our knowledge, this represents the first reported instance highlighting cutaneous AL amyloidosis and EED as primary clinical presentations in association with IgA monoclonal gammopathy.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eThe patient, a 78-year-old male, presented with a six-year history of multiple ecchymoses, purple-red papules, nodules, and plaques distributed on his ears, trunk, limbs, hands, and feet. Mild continuous pruritus was reported but resolved spontaneously. He was misdiagnosed as erythema multiforme for a long time and received symptomatic treatment without improving. Additionally, he had developed blood blisters and ulcers on his feet over the past two weeks which caused significant pain. There was no family history of hematologic or autoimmune diseases. Physical examination revealed multiple purple-red papules, nodules, and plaques affecting his auricles, trunk, limbs including necks, hands, and feet (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Furthermore, the lateral margins of his right foot exhibited large ecchymoses accompanied by ulcers. Laboratory investigation revealed an elevated serum IgA level (6.19 g/L; reference range 0.7-4.0 g/L). Serum protein electrophoresis demonstrated increased levels of β-globulin (15%; reference range 7.0\u0026ndash;11.0%) and γ-globulin (19.5%; reference range 9.0\u0026ndash;18.0%). Additionally, serum immunofixation electrophoresis confirmed the presence of monoclonal IgA λ FLCs, while serum κ FLCs were measured at 24.00 mg/L (reference range 6.7-22.4mg/L) and serum λ FLCs were measured at 90.00 mg/L (reference range 8.3\u0026ndash;27 mg/L), resulting in a κ/λ ratio of 0.26 (reference range: 0.26\u0026ndash;1.65). Examination for early renal injury revealed a urine microalbumin level of 0.7mg/24h (reference value \u0026lt;0.4mg/24h), urine κ FLCs of 17.60mg/24h (reference value\u0026lt;14 .20mg/24h), and urine λ FLCs of 19 .5mg/24h (reference value\u0026lt;7 .80mg/24h) with a κ/λ ratio consistent with the reference range(κ/λ\u0026thinsp;=\u0026thinsp;0.26). The urine immunofixation electrophoresis test produced negative findings. Normal results were obtained from additional laboratory tests, such as routine blood, urine, and stool examinations; clotting assessments; as well as liver and renal function evaluations. Measurements of 24-hour urinary protein excretion levels along with troponin I and proBNP concentrations fell within the normal range. Negative results were observed for hepatitis B virus markers, human immunodeficiency virus antigen/antibody testing, Treponema pallidum particle agglutination assay, antinuclear antibody screening, as well as tumor marker analysis. No abnormalities were detected in the electrocardiogram recordings or during the echocardiographic examination or imaging studies such as chest X-ray or abdominal color Doppler ultrasound. The bone marrow aspiration biopsy revealed the presence of rouleaux formations composed predominantly of mature erythrocytes with a proportionate representation of 2% proplasmacytes. Flow cytometry analysis of bone marrow revealed that abnormal monoclonal plasma cells accounted for 0.32% of the total number of nucleated bone marrow cells.The aberrant expression of CD38, CD138, CD200, CXCR4, and cIgλ was observed in these cells while the expression of CD34, CD117, CD19, CD20, CD7, CD5, CD33, CD10, CD56, CD13, CD22, CD27, CD28, and cIgκ was lost. The biopsy from the lateral margin of the foot lesion revealed eosinophilic amorphous material deposition within the dermis. This material exhibited positive Congo red staining and displayed apple-green birefringence under polarized light microscopy. Perivascular infiltrates consisting of lymphocytes, plasma cells, neutrophils, and eosinophils were observed in the dermis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Immunohistochemical staining confirmed the presence of κ and λ chain-positive plasma cells consistent with AL amyloidosis. Furthermore, the biopsy from the lesion on the left arm demonstrated a perivascular infiltrate primarily composed of lymphocytes and neutrophils along with extravasation of red blood cells in the dermis. Fibrinoid necrosis of small vessels, leukocytoclasia and eosinophilic amorphous material around vessels were observed. This material exhibited positive Congo red staining and displayed apple-green birefringence under polarized light microscopy, indicating the presence of amyloidosis accompanied by leukocytoclastic vasculitis (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Immunohistochemical staining (IHC) of skin biopsies revealed positive expression of both κ and λ light chains, as well as scattered cells expressing κ and λ light chains in the dermis. In situ hybridization (ISH) results from skin biopsies showed scattered positivity for both κ and λ light chains without evidence of clonality. Based on physical examination, laboratory tests, and histopathological findings, the patient was diagnosed with IgA monoclonal gammopathy, cutaneous AL amyloidosis, and EED. Subsequently, the patient was transferred to the hemato-oncology department for further treatment. During a 5-year follow-up period, intermittent occurrence of skin lesions persisted without significant changes observed in blood system examinations. Symptomatic treatment (oral Dapsone) was provided while regular follow-up appointments were scheduled.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMonoclonal gammopathy of clinical significance (MGCS) refers to non-malignant monoclonal gammopathies that result in substantial disease burden. As per the International Myeloma Working Group, MGCS is characterized by the presence of a monoclonal immunoglobulin or light chain, symptoms or clinical manifestations attributed to the presence of monoclonal protein, and not meeting diagnostic criteria for multiple myeloma or other lymphoplasmacytic disorders [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAccording to Daoud \u0026amp; al., monoclonal gammopathy of skin significance can be classified into four distinct groups along with MGCS [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Group 1 dermatosis results from infiltration, proliferation, and diffusion of malignant plasma cells in the skin, such as Waldenstr\u0026ouml;m's macroglobulinemia and myeloma, or from M-protein deposition, such as AL amyloidosis and cryoglobulinemia [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Group 2 dermatosis is closely associated with non-malignant monoclonal gammopathy where pathogenesis may arise from total or partial deposition of monoclonal immunoglobulins along with autoantibody activity and cytokine-mediated inflammation including scleromyxedema, pyoderma gangrenosum, acute febrile neutrophilic dermatosis (Sweet disease), or EED [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAL amyloidosis is characterized by the abnormal production of monoclonal κ and λ light chains, which serve as the substrate for amyloid fibril formation and subsequent deposition in various organs, resulting in organ damage and clinical manifestations [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The kidney, peripheral nerves, and skin are among the most commonly affected organs [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Dermatological manifestations of AL amyloidosis can vary widely, including purpura, papules, plaques, nodules, hemorrhagic or non-hemorrhagic bullae, subcutaneous nodules, alopecia and scleroderma-like changes. Oral involvement may encompass macroglossia, tongue induration, and gum bleeding. Nail dystrophy characterized by onychorrhexis, onychoschizia, and nail splitting is an exceedingly rare manifestation. Most of these cutaneous disorders are nonspecific; however, macroglossia and periorbital purpura represent specific clinical manifestations of AL amyloidosis. A tissue biopsy stained with Congo red that demonstrates apple-green birefringence in amyloid deposits is imperative for the diagnosis of AL amyloidosis. It is essential to confirm that the amyloid comprises immunoglobulin light chains. Laser capture mass spectroscopy is considered the gold standard for confirming the composition of the amyloid protein and distinguishing AL amyloidosis from other forms [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. There are two subtypes of AL amyloidosis: AL-κ and more commonly, AL-λ. The higher prevalence of AL-λ likely reflects its propensity to form β-pleated sheets. Overall, both AL-κ and AL-λ exhibit common histopathologic changes [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Our patient presented with an IgA-λ monoclonal gammopathy associated with AL-λ subtype. However, potential differences in clinical manifestations, histologic findings, and clinical significance between the two subtypes of AL amyloidosis remain unclear.\u003c/p\u003e \u003cp\u003eEED is a rare and chronic dermatosis characterized by leukocytoclastic vasculitis. The cutaneous manifestations of EED are typically described as erythematous to violaceous papules, plaques, or nodules [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. It primarily affects the extensor surfaces of joints, axilla, posterior auricular area, buttocks, soles, larynx, and acral sites. Some patients with EED may experience non-cutaneous manifestations such as arthralgia, scleritis, panuveitis, ulcerative keratitis, and neuropathy [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. EED is frequently observed in association with monoclonal gammopathy, particularly IgA monoclonal gammopathy or multiple myeloma. Additionally, it can be found in conjunction with numerous infectious and hematologic diseases, malignancies,and neutrophilic dermatoses as well as autoimmune and inflammatory diseases. Histopathologically, early lesions exhibit characteristic leukocytoclastic vasculitis with neutrophilic infiltrates surrounding blood vessels from the upper to mid-dermis, accompanied by eosinophils, lymphocytes, plasma cells, and nuclear debris. With disease progression, late-stage lesions demonstrate granulation tissue formation and storiform fibrosis. Additionally, focal areas of neutrophilic vasculitis may be observed. The etiology of EED remains poorly understood but is postulated to involve immune complex-mediated mechanisms that activate complement pathways, induce neutrophil infiltration and release of destructive enzymes, trigger IL-8 activation for selective recruitment of leukocytes to blood vessels resulting in subsequent leukocytoclastic vasculitis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo investigate the association between EED and IgA monoclonal gammopathy as well as AL amyloidosis, we conducted a comprehensive search of case reports on the electronic PubMed database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e; up to December 2024) from 1992 to 2024 using the keywords \"erythema elevatum diutinum (EED)\" and \"IgA monoclonal gammopathy (IgA paraproteinemia)\". Our search identified a total of 19 cases reporting EED associated with IgA monoclonal gammopathy (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) [\u003cspan additionalcitationids=\"CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Additionally, seven of these patients presented with other complications or comorbidities, including pyoderma gangrenosum in three cases, Wegener granulomatosis in one case, Hepatitis C in one case, oropharyngeal ulceration in two cases, and Hashimoto's disease in one case. Among the 19 EED patients reported in the literature, serum immunofixed electrophoresis was performed for 14 individuals with IgA monoclonal gammopathy. Of these cases, nine showed κ light chain positivity while five exhibited λ light chain positivity. ANCA examination was conducted for five out of the 19 EED patients mentioned in the literature: three were ANCA positive and two were ANCA negative; notably, this particular patient was ANCA negative.The authors propose that further investigation is warranted to elucidate the role of ANCA in the pathogenesis of EED. To date, no documented instances have been reported regarding the coexistence of AL amyloidosis and EED in association with IgA monoclonal gammopathy.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLiterature review of published cases of Erythema elevatum diutinum associated with IgA monoclonal gammopathy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAuthor(date)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge(yr)/ sex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLaboratory examination\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAccompany diseases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYiannias JA\u003c/p\u003e \u003cp\u003e\u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(1992)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35/UK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis IgAκ(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo details\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo details\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYiannias JA\u003c/p\u003e \u003cp\u003e\u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(1992)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37/UK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis IgAκ(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo details\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo details\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWilkinson SM \u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(1992)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis IgAκ(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDapsone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWilkinson SM \u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(1992)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis IgA λ(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIntralesional triamcinolone,\u003c/p\u003e \u003cp\u003edapsone,\u003c/p\u003e \u003cp\u003eexcision\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo effect\u003c/p\u003e \u003cp\u003eNo tolerated\u003c/p\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWilkinson SM \u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(1992)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis IgA λ(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDapsone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWilkinson SM \u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(1992)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis IgA λ(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDapsone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGina M\u003c/p\u003e \u003cp\u003e\u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(1993)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis\u003c/p\u003e \u003cp\u003eIgAκ(+), ANCA༈+༉\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eWegener's granulomatosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDapsone,\u003c/p\u003e \u003cp\u003emethylprednisolonecy, clophosphamide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWayte JA et al [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(1995)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis\u003c/p\u003e \u003cp\u003eIgAκ(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePyoderma gangrenosum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePrednisolone,\u003c/p\u003e \u003cp\u003edapsone,\u003c/p\u003e \u003cp\u003eminocycline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChow RK et al [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(1996)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIgA 8g/L (0.7\u0026ndash;3.9 g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePlasma exchange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChowdhury MM \u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(2002)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis IgAκ(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDapsone, MTX, sulfapyridine, nicotinamide and colchicine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eProgressed\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSimpson R\u003c/p\u003e \u003cp\u003e\u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(2010)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eANCA(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo details\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo details\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSimpson R\u003c/p\u003e \u003cp\u003e\u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(2010)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eANCA(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePyoderma gangrenosum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo details\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo details\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThomas CL \u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(2015)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis\u003c/p\u003e \u003cp\u003eIgAκ(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eExcision\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHealed\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eManni E\u003c/p\u003e \u003cp\u003e\u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(2015)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIgA level 760 mg/dL\u003c/p\u003e \u003cp\u003eImmunoelectrophoresisIgAκ(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePlasma exchange, Thalidomide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatnala GP\u003c/p\u003e \u003cp\u003e\u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(2016)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis IgA λ(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDapsone,\u003c/p\u003e \u003cp\u003edoxycycline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBansal R\u003c/p\u003e \u003cp\u003eet al [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(2017)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIgA 2290mg/dl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHepatitis C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDapsone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKentley J\u003c/p\u003e \u003cp\u003eet al [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(2017)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis IgA λ(+)\u003c/p\u003e \u003cp\u003eIgA 6.29(0.8-4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOropharyngeal ulceration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eColchicine,\u003c/p\u003e \u003cp\u003edapsone,\u003c/p\u003e \u003cp\u003ehydroxychloroquine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eH\u0026uuml;gel R\u003c/p\u003e \u003cp\u003eet al [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(2018)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis IgAκ(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePyoderma gangrenosum,\u003c/p\u003e \u003cp\u003eoropharyngeal ulceration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMethylprednisolone,\u003c/p\u003e \u003cp\u003edapsone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJacob JS\u003c/p\u003e \u003cp\u003eet al [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e(2021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmunoelectrophoresis IgA(+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHashimoto's disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIndomethacin,\u003c/p\u003e \u003cp\u003eintralesional triamcinolone,\u003c/p\u003e \u003cp\u003edapsone,\u003c/p\u003e \u003cp\u003eexcision\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eImproved\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cem\u003eF: Female; M: Male\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe primary objective of AL amyloidosis treatment is to promptly reduce the production of amyloidogenic light chains, prevent further deposition of amyloid protein in vital organs, and ameliorate or reverse progressive damage to affected organs. The main approach involves chemotherapy targeting the underlying clonal plasma cell dyscrasia. Approximately 5% of AL amyloidosis patients present with localized lesions in various sites, such as the bladder, throat, stomach, colon, skin, lungs, and urinary tract (as observed in our patient) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. These individuals typically do not develop systemic disease; therefore, observation of asymptomatic lesions or surgery and radiotherapy is preferred. Dapsone serves as the first-line treatment for EED due to its antimicrobial properties that impair neutrophil chemotaxis and function. Other therapeutic options include NSAIDs, niacinamide, tetracyclines, chloroquine, colchicine, and plasmapheresis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Additionally,surgical excision may be considered if fibrotic nodules exhibit a poor response to dapsone and are limited in extent. Our patient has been regularly followed up for 5 years without evident systemic damage and with slow progression of lesions. Hence, current management involves only symptomatic treatment along with close monitoring.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe present a case involving an elderly male patient who endured misdiagnosis and inappropriate treatment for a duration of six years. Ultimately, through comprehensive laboratory evaluations and histopathological biopsies, he was diagnosed with IgA MG associated cutaneous AL amyloidosis combined with EED. We underscore the critica\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003el role\u003c/span\u003e of skin pathology in diagnosing dermatological manifestations associated with MG. Additionally, we conduct a literature review on EED associated with IgA MG, highlighting the necessity for further research to clarify the involvement of ANCA in the pathogenesis of EED.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e Bing Han: Writing \u0026ndash; review \u0026amp; editing, Writing \u0026ndash; original draft, Software, Resources, Data curation. Junfeng Zhou: Investigation. Hesong Liu: Resources. Shanshan Li and Hong Wang: Supervision, Conceptualization, Writing \u0026ndash; review \u0026amp; editing, Writing \u0026ndash; original draft, Methodology, Formal analysis, Conceptualization. Hong Wang and Shanshan Li contributed equally to the work and should be regarded as co-corresponding authors. All authors take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.\u0026nbsp;\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e No funding or sponsorship was received for the publication of this study.\u0026nbsp;\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eClinical Trial Registration\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePatient consent statement\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eWritten informed consent was obtained from the patient.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u0026nbsp;\u003c/strong\u003eThe patient has consented to the submission of the case report to the journal.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePermission to reproduce material from other sources\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThe authors have no competing interests as defined by Springer, or other interests that might be perceived to influence the results and/or discussion reported in this paper.\u003c/p\u003e\n\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eClaveau JS, Wetter DA, Kumar S (2022) Cutaneous manifestations of monoclonal gammopathy. Blood Cancer J 12(4):58. https://doi.org/10.1038/s41408-022-00661-1\u003c/li\u003e\n\u003cli\u003eDaoud MS, Lust JA, Kyle RA, Pittelkow MR (1999) Monoclonal gammopathies and associated skin disorders J Am Acad Dermatol 40(4):507\u0026ndash;35. https://doi.org/10.1016/s0190-9622(99)70434-2\u003c/li\u003e\n\u003cli\u003eFermand JP, Bridoux F, Dispenzieri A, Jaccard A, Kyle RA, Leung N, et al (2018) Monoclonal gammopathy of clinical significance: a novel concept with therapeutic implications Blood 132(14):1478-85. https://doi.org/10.1182/blood-2018-04-839480\u003c/li\u003e\n\u003cli\u003eSchmidt T, Callander N (2020) Diagnosis and Management of Monoclonal Gammopathy and Smoldering Multiple Myeloma. J Natl Compr Canc Netw 18(12):1720-9. https://doi.org/10.6004/jnccn.2020.7660\u003c/li\u003e\n\u003cli\u003eGertz MA (2020) Immunoglobulin light chain amyloidosis: 2020 update on diagnosis, prognosis, and treatment. Am J Hematol 95(7):848-60. https://doi.org/ 10.1002/ajh.25819\u003c/li\u003e\n\u003cli\u003eFermand JP, Bridoux F, Dispenzieri A, Jaccard A, Kyle RA, Leung N, et al (2018) Monoclonal gammopathy of clinical significance: a novel concept with therapeutic implications. Blood 132(14):1478-85. https://doi.org/ 10.1182/blood-2018-04-839480\u003c/li\u003e\n\u003cli\u003eGertz MA (2024) Immunoglobulin light chain amyloidosis: 2024 update on diagnosis, prognosis, and treatment. Am J Hematol 99(2):309-24. https://doi.org/ 10.1002/ajh.27177\u003c/li\u003e\n\u003cli\u003eWu H, L\u0026apos;Imperio V, Rossi M, Kapp ME, Paueksakon P (2023) Differences between \u0026kappa; and \u0026lambda; light chain amyloidosis analyzed by a pathologic scoring system. Am J Clin Pathol 160(2):144-9. https://doi.org/ 10.1093/ajcp/aqad017\u003c/li\u003e\n\u003cli\u003eAwan BE, Noda Y, Yabuno Y, Hokazono Y, Ansai S, Ogawa R (2021) A Case of Erythema Elevatum Diutinum (EED) Exhibiting A Keloid-Like Appearance. Dermatol Ther (Heidelb) 11(6):2235-40. https://doi: 10.1007/s13555-021-00639-0\u003c/li\u003e\n\u003cli\u003eGrabbe J, Haas N, M\u0026ouml;ller A, Henz BM (2000) Erythema elevatum diutinum--evidence for disease-dependent leucocyte alterations and response to dapsone. Br J Dermatol 43(2); 415-20. https://doi.org/10.1046/j.1365-2133.2000.03673.x\u003c/li\u003e\n\u003cli\u003eYiannias JA, el-Azhary RA, Gibson LE (1992) Erythema elevatum diutinum: a clinical and histopathologic study of 13 patients. J Am Acad Dermatol 26(1):38-44. https://doi.org/10.1016/0190-9622(92)70003-x\u003c/li\u003e\n\u003cli\u003eWilkinson SM, English JS, Smith NP, Wilson-Jones E, Winkelmann RK (1992) Erythema elevatum diutinum: a clinicopathological study. Clin Exp Dermatol 17(2):87-93. https://doi.org/10.1111/j.1365-2230.1992.tb00171.x\u003c/li\u003e\n\u003cli\u003eKavanagh GM, Colaco CB, Bradfield JW, Archer CB (1993) Erythema elevatum diutinum associated with Wegener\u0026apos;s granulomatosis and IgA paraproteinemia. J Am Acad Dermatol 28(5):846-9. https://doi.org/ 10.1016/0190-9622(93)70115-a\u003c/li\u003e\n\u003cli\u003eWayte JA, Rogers S, Powell FC (1995) Pyoderma gangrenosum, erythema elevatum diutinum and IgA monoclonal gammopathy. Australas J Dermatol 36(1):21-23. https://doi.org/10.1111/j.1440-0960.1995.tb00919.x\u003c/li\u003e\n\u003cli\u003eChow RK, Benny WB, Coupe RL, Dodd WA, Ongley RC (1996) Erythema elevatum diutinum associated with IgA paraproteinemia successfully controlled with intermittent plasma exchange. Arch Dermatol 132(11):1360-4\u003c/li\u003e\n\u003cli\u003eChowdhury MM, Inaloz HS, Motley RJ, Knight AG (2002) Erythema elevatum diutinum and IgA paraproteinaemia: \u0026apos;a preclinical iceberg\u0026apos;. Int J Dermatol 41(6):368-70. https://doi.org/10.1111/j.1365-4632.2002.1432_4.x\u003c/li\u003e\n\u003cli\u003eSimpson R, Crichlow SM, Alexandroff AB, Harman KE (2010) A case series of three patients with erythema elevatum diutinum in association with paraproteinaemia and IgA antineutrophil cytoplasmic antibodies. British Journal of Dermatology 163(1):27\u003c/li\u003e\n\u003cli\u003eThomas CL, Ffolkes L, Akhras V (2015) A case of mistaken identity: unilateral erythema elevatum diutinum associated with IgA paraproteinaemia. Clin Exp Dermatol 40(7):761-4. https://doi.org/10.1111/ced.12622\u003c/li\u003e\n\u003cli\u003eManni E, Cervadoro E, Papineschi F (2015) Case of erythema elevatum diutinum associated with IgA paraproteinemia successfully controlled with thalidomide and plasma exchange. Ther Apher Dial 19(2):195-6. https://doi.org/10.1111/1744-9987.12234\u003c/li\u003e\n\u003cli\u003ePatnala GP, Sunandini AP, Rayavarapu R, Yandapalli PS (2016) Erythema elevatum diutinum in association with IgA monoclonal gammopathy: A rare case report. Indian Dermatol Online J 7(4):300-3. https://doi.org/ 10.4103/2229-5178.185472\u003c/li\u003e\n\u003cli\u003eBansal R, Aron J, Rajnish I (2017) Erythema Elevatum Diutinum. Am J Med Sci 353(2):189. https://doi.org/10.1016/j.amjms.2016.05.005\u003c/li\u003e\n\u003cli\u003eKentley J, Marshall C, Bewley A (2017) Erythema elevatum diutinum-associated with loss of the uvula. JAAD Case Rep 3(3):212-4. https://doi.org/10.1016/j.jdcr.2017.02.007\u003c/li\u003e\n\u003cli\u003eH\u0026uuml;gel R, Brasch J, Yordanova I, Schr\u0026ouml;der JO, Fazel A, Gl\u0026auml;ser R, et al (2018) Erythema elevatum diutinum associated with severe oropharyngeal ulceration and pyoderma gangrenosum. J Dtsch Dermatol Ges 16(5):617-20. https://doi.org/10.1111/ddg.13508\u003c/li\u003e\n\u003cli\u003eJacob JS, Tschen J (2021) Atypical Presentation of Erythema Elevatum Diutinum in a Patient With Hashimoto\u0026apos;s Disease. Cureus 13(9):e18214. https://doi.org/10.7759/cureus.18214\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Cutaneous AL amyloidosis, Erythema elevatum diutinum, IgA monoclonal gammopathy, case report, literature review","lastPublishedDoi":"10.21203/rs.3.rs-5785089/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5785089/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMonoclonal gammopathy (MG) associated with dermatological disorders, which is classified as monoclonal gammopathy of clinical significance (MGCS), represents a well-established complication. These dermatologic conditions are linked to the infiltration and proliferation of malignant plasma cells or the deposition of monoclonal immunoglobulin in nonmalignant monoclonal gammopathy. Immunoglobulin light chain amyloidosis (AL amyloidosis) is a clonal, non-proliferative plasma cell disorder characterized by the deposition of fragments of immunoglobulin light chains in tissues. Erythema elevatum diutinum (EED) is clearly associated with monoclonal gammopathy, particularly IgA monoclonal gammopathy, although the pathomechanism has not been clearly established. In this article, we report an extremely rare case involving the coexistence of cutaneous light chain amyloidosis (AL amyloidosis) and erythema elevatum diutinum (EED) as the presenting features of IgA monoclonal gammopathy, which to our knowledge is the first reported case. During a 5-year follow-up period, intermittent occurrence of skin lesions persisted without significant changes observed in blood system examinations. Furthermore, we provided a comprehensive review of the existing literature on EED associated with IgA MG to enhance the understanding of skin significance of MG.\u003c/p\u003e","manuscriptTitle":"Cutaneous light chain amyloidosis and erythema elevatum diutinum as the presenting features of IgA monoclonal gammopathy: a rare case report and comprehensive literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 18:41:02","doi":"10.21203/rs.3.rs-5785089/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2025-09-04T15:31:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-01T19:54:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"233052157710609314084744200655373222351","date":"2025-08-24T19:43:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"128522183959485182367115136303795495216","date":"2025-04-09T05:49:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-28T15:13:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-28T08:46:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Hematology","date":"2025-03-19T02:44:06+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f8f14ffe-22a1-44b5-84bf-50f023881fbd","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T16:25:40+00:00","versionOfRecord":{"articleIdentity":"rs-5785089","link":"https://doi.org/10.1007/s00277-025-06621-6","journal":{"identity":"annals-of-hematology","isVorOnly":false,"title":"Annals of Hematology"},"publishedOn":"2025-10-20 16:16:35","publishedOnDateReadable":"October 20th, 2025"},"versionCreatedAt":"2025-03-31 18:41:02","video":"","vorDoi":"10.1007/s00277-025-06621-6","vorDoiUrl":"https://doi.org/10.1007/s00277-025-06621-6","workflowStages":[]},"version":"v1","identity":"rs-5785089","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5785089","identity":"rs-5785089","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}