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Henoch–Schönlein Purpura Associated with Lung Cancer: When Paraneoplastic Manifestations Impede Oncological Management

Henoch–Schönlein Purpura Associated with Lung Cancer: When Paraneoplastic Manifestations Impede... Hindawi Case Reports in Immunology Volume 2021, Article ID 8847017, 4 pages https://doi.org/10.1155/2021/8847017 Case Report Henoch–Schonlein Purpura Associated with Lung Cancer: When Paraneoplastic Manifestations Impede Oncological Management 1,2 2 2 1 1 Elo¨ ıse Philippe , Aude Barnier, Juliette Menguy, Gilles Robinet, Gilles Que ´ re ´ , 2 1 Francis Couturaud, and Renaud Descourt Institut De Canc´erologie, CHU Morvan, Brest 29200, France Service De Pneumologie, EA3878-GETBO, Universit´e De Bretagne Occidentale, CHU Cavale Blanche, Boulevard Tanguy-Prigent, Brest 29200, France Correspondence should be addressed to Elo¨ıse Philippe; eloise.philippe@chu-brest.fr Received 2 August 2020; Revised 21 December 2020; Accepted 28 January 2021; Published 8 February 2021 Academic Editor: Claudio Pignata Copyright © 2021 Elo¨ıse Philippe et al. )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. Background. Henoch–Schonlein ¨ purpura (HSP) is an uncommon syndrome that mostly occurs in children, in whom it is frequently triggered by infections. In contrast, HSP in adults is more frequently of neoplastic origin. Case Presentation. We report HSP associated with a locally advanced lung squamous cell carcinoma that was considered a paraneoplastic syndrome. Systemic corticosteroids were given because a kidney biopsy revealed active glomerulonephritis. Concomitant chemoradiotherapy achieved a partial response of the lung tumor. Consolidation immunotherapy (programmed death protein-1-ligand-1 (PD-L1) inhibitor) was cancelled because HSP is known to be an autoimmune vasculitis, and long-term corticosteroid therapy was pursued. Conclusion. Further prospective studies are needed to evaluate the effect of anti-PD-(L) 1 immunotherapies on autoimmune manifestations. appeared on hospitalization day 2. )e skin biopsy showed 1. Introduction leukocytoclastic vasculitis with immunoglobulin A deposits. Henoch–Schonlein ¨ purpura (HSP) is an uncommon syn- Hyperthermia worsened and he experienced an impure drome rarely observed in adults. Its association with cancer nephrotic syndrome (acute renal failure, hematuria) on day raises the question of a causal link. Its clinical manifestations 5 (proteinuria 5 g/24 h). )e kidney biopsy showed prolif- most frequently involve skin, joints, gastrointestinal tract, erative glomerulonephritis with IgA deposits, suggesting and glomeruli. We describe this paraneoplastic vasculitis renal localization of HSP (Figure 2). Other vasculitides were associated with lung squamous cell carcinoma (SCC). excluded because all immune markers tested were negative (Table 1). Systemic corticosteroids were started to treat active histological lesions (500 mg/d solumedrol bolus for 3 2. Case Presentation days, followed by progressive tapering over a total duration of 6 months). Proteinuria rapidly decreased to 1.53 G/24 h A 59-year-old man, an active smoker with chronic bron- over 10 days. Fever and skin rash resolved in 7 days. Based chitis, consulted for a cough that had persisted for several on the F-fluorodeoxyglucose-positron-emission tomog- weeks. His chest computed tomography (CT) scan revealed a raphy (FDG-PET) scan, the tumor was ranked cT4N2M0. spiculated mass in the left upper lobe infiltrating the me- Concomitant chemoradiotherapy (CRT) (3 cycles of cis- diastinum (Figure 1(a)). Histology of bronchial biopsies platin-vinorelbine and 66 Gy of radiation (2 Gy/fraction) revealed SCC. Ten days later, he was hospitalized for a fever over a total treatment duration of 8 weeks) achieved a partial that persisted despite first-line antibiotics, associated with an response at 4 weeks (Figure 1(b)). Consolidation immu- inflammatory syndrome (C-reactive protein, 51 mg/L; leu- notherapy with antiprogrammed death protein-1-ligand-1 kocytes, 11.5 G/L). Vascular purpura of the lower extremities 2 Case Reports in Immunology (a) (b) Figure 1: CT scans showing (a) left upper lobe SCC at diagnosis and (b) a partial response to chemoradiotherapy at 4 weeks. (a) (b) Figure 2: Histology of a kidney biopsy. (a) Endocapillary proliferation (stained with hematoxylin-eosin-saffron; ×300). (b) Immuno- fluorescent labeling of IgA deposits showing a diffuse, granular, parietal pattern (×400). (PD-L1) (durvalumab) after CRT was discussed in a mul- CT scan showed enlargement of the irradiated residual tu- tidisciplinary meeting but excluded because of the initial mor. Histology of fibroscopy-obtained bronchial biopsies autoimmune manifestations and the ongoing corticosteroid found SCC infiltration of a left superior lobar exophytic bud therapy. Twelve months after completing CRT, a follow-up and FDG-PET scan indicated hypermetabolism of the lung Case Reports in Immunology 3 Table 1: Serology results for autoimmunity. preexisting autoimmune disease were excluded from clinical trials and early access programs. Retrospective series sug- Autoimmune-testing target Result gests that worsening of preexisting autoimmune conditions Antinuclear antibodies Positive (1/320) is common in lung cancer patients treated with anti-PD-(L) Anti-DNA antibodies Negative 1 and that immunosuppressants (like corticosteroids) may Histone antibodies Negative lower the efficacy of immunotherapies [8]. Current data are Anticentromeres antibodies Negative controversial regarding the use of immune-checkpoint in- Antibasement membrane antibodies Negative hibitors in patients with preexisting autoimmune disease. A Rheumatoid factor Negative Polynuclear anticytoplasmic antibodies Negative recent nationwide, multicenter, cohort study assessed the Serum free light-chain assay Normal safety and efficacy of immune-checkpoint inhibitors as Complement protein assay Normal cancer therapy for patients with preexisting autoimmune diseases [9]. According to its results, the occurrence of an immune-related adverse effect and/or flare of preexisting mass with no sign of distant metastases, thereby confirming autoimmune disease was frequent (71%) but mostly man- localized recurrence. )e latter was not associated with a ageable without immune-checkpoint inhibitor vasculitis relapse. discontinuation. We obtained the patient’s written informed consent for In conclusion, as the indications of immunotherapy publication. become more and more numerous, further studies are needed to evaluate the efficacy and overall safety of im- munotherapy for patients with advanced or locally advanced 3. Discussion non-small-cell lung carcinoma and preexisting or con- HSP or rheumatoid purpura is a systemic small-vessel comitant paraneoplastic autoimmune disease. vasculitis associated with tissue deposits of IgA immune complexes. An external antigenic attack inducing an ab- Abbreviations normal response of a faulty or immature immune system HSP: Henoch–Schonlein ¨ purpura might be the pathophysiological mechanism. Several organs CRT: Chemoradiotherapy may be affected, with symptomatic deposits in skin, joints, CT: Computed tomography and gastrointestinal tract being the most common. FDG-PET: F-fluorodeoxyglucose-positron-emission )e outcome is mainly conditioned by renal involve- tomography ment. HSP is considered to be a childhood pathology but can PD-L1: Antiprogrammed death protein-1-ligand-1 occur in adults, sometimes associated with solid-organ SCC: Squamous cell carcinoma. malignancies [1]. Abnormal deposits might be secondary to an immune reaction against tumor antigens. Failure to clear immune complexes and similarity of tumor antigens and Data Availability endothelial cell antigens have also been advanced. Although )e clinical data used to support the findings of this study the cancer-HSP relationship is still unclear, several case are included within the report. reports have described this association. About 5% of vasculitis patients have associated cancer Conflicts of Interest (2/3 hematological malignancies and 1/3 solid cancer). Vasculitis regression during cancer treatment is commonly )e authors declare that they have no conflicts of interest considered evidence of a paraneoplastic syndrome. Para- regarding the publication of this article. neoplastic vasculitides are uncommon (frequency 1/80,800) [2], among which only 6.8% are HSP. When paraneoplastic Authors’ Contributions vasculitides occur, they are often associated with lung cancer, especially SCC or small cell lung cancer [3]. A recent All authors participated in the care of the patient and systematic review reported 10 patients with both lung cancer contributed to the medical literature search. EP was re- (two small-cell lung cancers, three adenocarcinomas, four sponsible for the pathology report. RD and FC supervised SCCs, and one with unspecified non-small-cell lung cancer) this report. All authors read and approved the final and cutaneous vasculitis [4]. Paraneoplastic purpura in our manuscript. patient is plausible. An infectious origin was excluded based on clinical improvement with corticosteroids alone. Other Acknowledgments possible triggering factors were also excluded (medication, allergic reaction, and another autoimmune disease) )e authors thank Ms. Janet Jacobson for editorial (Table 1). assistance. Autoimmune paraneoplastic manifestations raise doubt as to the indication of immunotherapy for advanced or References locally advanced non-small-cell lung cancer. )e beneficial impacts of immunotherapy on overall survival and pro- [1] J. M. Zurada, K. M. Ward, and M. E. Grossman, “Henoch- gression-free survival are known [5–7], but patients with Schonlein ¨ purpura associated with malignancy in adults,” 4 Case Reports in Immunology Journalofthe AmericanAcademyofDermatology, vol. 55, no. 5, pp. S65–S70, 2006. [2] J. M. Greer, S. Longley, N. L. Edwards, G. J. Elfenbein, and R. S. Panush, “Vasculitis associated with malignancy experi- ence with 13 patients and literature review,” Medicine, vol. 67, no. 4, pp. 220–230, 1988. [3] R. Blanco, M. A. Gonzalez-Gay, ´ D. Ibañez, ´ C. Alba, and L. A. P´erez De Llano, “Henoch–Schonlein ¨ purpura as a clinical presentation of small cell lung cancer,” Clinical and Experi- mental Rheumatology, vol. 15, no. 5, pp. 545–547, 1997. [4] S. Holbrechts, J. Gorham, S. Sideris et al., “Autoimmune paraneoplastic syndromes associated to lung cancer: a sys- tematic review of the literature,” Lung Cancer, vol. 106, pp. 93–101, 2017. [5] S. J. Antonia, A. Villegas, D. Daniel et al., “Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC,” New England Journal of Medicine, vol. 379, no. 24, pp. 2342– 2350, 2018. [6] M. Reck, D. Rodr´ıguez-Abreu, A. G. Robinson et al., “Pem- brolizumab versus chemotherapy for PD-L1-positive non- small-cell lung cancer,” New England Journal of Medicine, vol. 375, no. 19, pp. 1823–1833, 2016. [7] L. Horn, D. R. Spigel, E. E. Vokes et al., “Nivolumab versus docetaxel in previously treated patients with advanced non- small-cell lung cancer: two-year outcomes from two ran- domized, open-label, phase III trials (CheckMate 017 and CheckMate 057),” Journal of Clinical Oncology, vol. 35, no. 35, pp. 3924–3933, 2017. [8] K. C. Arbour, L. Mezquita, N. Long et al., “Impact of baseline steroids on efficacy of programmed cell death-1 and pro- grammed death-ligand 1 blockade in patients with non-small- cell lung cancer,” Journal of Clinical Oncology, vol. 36, no. 28, pp. 2872–2878, 2018. [9] A. Tison, G. Quer ´ e, ´ L. Misery et al., “Safety and efficacy of immune checkpoint inhibitors in patients with cancer and preexisting autoimmune disease: a nationwide, multicenter cohort study,” Arthritis & Rheumatology, vol. 71, no. 12, pp. 2100–2111, 2019. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Immunology Hindawi Publishing Corporation

Henoch–Schönlein Purpura Associated with Lung Cancer: When Paraneoplastic Manifestations Impede Oncological Management

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Copyright © 2021 Éloïse Philippe et al. This 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.
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Abstract

Hindawi Case Reports in Immunology Volume 2021, Article ID 8847017, 4 pages https://doi.org/10.1155/2021/8847017 Case Report Henoch–Schonlein Purpura Associated with Lung Cancer: When Paraneoplastic Manifestations Impede Oncological Management 1,2 2 2 1 1 Elo¨ ıse Philippe , Aude Barnier, Juliette Menguy, Gilles Robinet, Gilles Que ´ re ´ , 2 1 Francis Couturaud, and Renaud Descourt Institut De Canc´erologie, CHU Morvan, Brest 29200, France Service De Pneumologie, EA3878-GETBO, Universit´e De Bretagne Occidentale, CHU Cavale Blanche, Boulevard Tanguy-Prigent, Brest 29200, France Correspondence should be addressed to Elo¨ıse Philippe; eloise.philippe@chu-brest.fr Received 2 August 2020; Revised 21 December 2020; Accepted 28 January 2021; Published 8 February 2021 Academic Editor: Claudio Pignata Copyright © 2021 Elo¨ıse Philippe et al. )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. Background. Henoch–Schonlein ¨ purpura (HSP) is an uncommon syndrome that mostly occurs in children, in whom it is frequently triggered by infections. In contrast, HSP in adults is more frequently of neoplastic origin. Case Presentation. We report HSP associated with a locally advanced lung squamous cell carcinoma that was considered a paraneoplastic syndrome. Systemic corticosteroids were given because a kidney biopsy revealed active glomerulonephritis. Concomitant chemoradiotherapy achieved a partial response of the lung tumor. Consolidation immunotherapy (programmed death protein-1-ligand-1 (PD-L1) inhibitor) was cancelled because HSP is known to be an autoimmune vasculitis, and long-term corticosteroid therapy was pursued. Conclusion. Further prospective studies are needed to evaluate the effect of anti-PD-(L) 1 immunotherapies on autoimmune manifestations. appeared on hospitalization day 2. )e skin biopsy showed 1. Introduction leukocytoclastic vasculitis with immunoglobulin A deposits. Henoch–Schonlein ¨ purpura (HSP) is an uncommon syn- Hyperthermia worsened and he experienced an impure drome rarely observed in adults. Its association with cancer nephrotic syndrome (acute renal failure, hematuria) on day raises the question of a causal link. Its clinical manifestations 5 (proteinuria 5 g/24 h). )e kidney biopsy showed prolif- most frequently involve skin, joints, gastrointestinal tract, erative glomerulonephritis with IgA deposits, suggesting and glomeruli. We describe this paraneoplastic vasculitis renal localization of HSP (Figure 2). Other vasculitides were associated with lung squamous cell carcinoma (SCC). excluded because all immune markers tested were negative (Table 1). Systemic corticosteroids were started to treat active histological lesions (500 mg/d solumedrol bolus for 3 2. Case Presentation days, followed by progressive tapering over a total duration of 6 months). Proteinuria rapidly decreased to 1.53 G/24 h A 59-year-old man, an active smoker with chronic bron- over 10 days. Fever and skin rash resolved in 7 days. Based chitis, consulted for a cough that had persisted for several on the F-fluorodeoxyglucose-positron-emission tomog- weeks. His chest computed tomography (CT) scan revealed a raphy (FDG-PET) scan, the tumor was ranked cT4N2M0. spiculated mass in the left upper lobe infiltrating the me- Concomitant chemoradiotherapy (CRT) (3 cycles of cis- diastinum (Figure 1(a)). Histology of bronchial biopsies platin-vinorelbine and 66 Gy of radiation (2 Gy/fraction) revealed SCC. Ten days later, he was hospitalized for a fever over a total treatment duration of 8 weeks) achieved a partial that persisted despite first-line antibiotics, associated with an response at 4 weeks (Figure 1(b)). Consolidation immu- inflammatory syndrome (C-reactive protein, 51 mg/L; leu- notherapy with antiprogrammed death protein-1-ligand-1 kocytes, 11.5 G/L). Vascular purpura of the lower extremities 2 Case Reports in Immunology (a) (b) Figure 1: CT scans showing (a) left upper lobe SCC at diagnosis and (b) a partial response to chemoradiotherapy at 4 weeks. (a) (b) Figure 2: Histology of a kidney biopsy. (a) Endocapillary proliferation (stained with hematoxylin-eosin-saffron; ×300). (b) Immuno- fluorescent labeling of IgA deposits showing a diffuse, granular, parietal pattern (×400). (PD-L1) (durvalumab) after CRT was discussed in a mul- CT scan showed enlargement of the irradiated residual tu- tidisciplinary meeting but excluded because of the initial mor. Histology of fibroscopy-obtained bronchial biopsies autoimmune manifestations and the ongoing corticosteroid found SCC infiltration of a left superior lobar exophytic bud therapy. Twelve months after completing CRT, a follow-up and FDG-PET scan indicated hypermetabolism of the lung Case Reports in Immunology 3 Table 1: Serology results for autoimmunity. preexisting autoimmune disease were excluded from clinical trials and early access programs. Retrospective series sug- Autoimmune-testing target Result gests that worsening of preexisting autoimmune conditions Antinuclear antibodies Positive (1/320) is common in lung cancer patients treated with anti-PD-(L) Anti-DNA antibodies Negative 1 and that immunosuppressants (like corticosteroids) may Histone antibodies Negative lower the efficacy of immunotherapies [8]. Current data are Anticentromeres antibodies Negative controversial regarding the use of immune-checkpoint in- Antibasement membrane antibodies Negative hibitors in patients with preexisting autoimmune disease. A Rheumatoid factor Negative Polynuclear anticytoplasmic antibodies Negative recent nationwide, multicenter, cohort study assessed the Serum free light-chain assay Normal safety and efficacy of immune-checkpoint inhibitors as Complement protein assay Normal cancer therapy for patients with preexisting autoimmune diseases [9]. According to its results, the occurrence of an immune-related adverse effect and/or flare of preexisting mass with no sign of distant metastases, thereby confirming autoimmune disease was frequent (71%) but mostly man- localized recurrence. )e latter was not associated with a ageable without immune-checkpoint inhibitor vasculitis relapse. discontinuation. We obtained the patient’s written informed consent for In conclusion, as the indications of immunotherapy publication. become more and more numerous, further studies are needed to evaluate the efficacy and overall safety of im- munotherapy for patients with advanced or locally advanced 3. Discussion non-small-cell lung carcinoma and preexisting or con- HSP or rheumatoid purpura is a systemic small-vessel comitant paraneoplastic autoimmune disease. vasculitis associated with tissue deposits of IgA immune complexes. An external antigenic attack inducing an ab- Abbreviations normal response of a faulty or immature immune system HSP: Henoch–Schonlein ¨ purpura might be the pathophysiological mechanism. Several organs CRT: Chemoradiotherapy may be affected, with symptomatic deposits in skin, joints, CT: Computed tomography and gastrointestinal tract being the most common. FDG-PET: F-fluorodeoxyglucose-positron-emission )e outcome is mainly conditioned by renal involve- tomography ment. HSP is considered to be a childhood pathology but can PD-L1: Antiprogrammed death protein-1-ligand-1 occur in adults, sometimes associated with solid-organ SCC: Squamous cell carcinoma. malignancies [1]. Abnormal deposits might be secondary to an immune reaction against tumor antigens. Failure to clear immune complexes and similarity of tumor antigens and Data Availability endothelial cell antigens have also been advanced. Although )e clinical data used to support the findings of this study the cancer-HSP relationship is still unclear, several case are included within the report. reports have described this association. About 5% of vasculitis patients have associated cancer Conflicts of Interest (2/3 hematological malignancies and 1/3 solid cancer). Vasculitis regression during cancer treatment is commonly )e authors declare that they have no conflicts of interest considered evidence of a paraneoplastic syndrome. Para- regarding the publication of this article. neoplastic vasculitides are uncommon (frequency 1/80,800) [2], among which only 6.8% are HSP. When paraneoplastic Authors’ Contributions vasculitides occur, they are often associated with lung cancer, especially SCC or small cell lung cancer [3]. A recent All authors participated in the care of the patient and systematic review reported 10 patients with both lung cancer contributed to the medical literature search. EP was re- (two small-cell lung cancers, three adenocarcinomas, four sponsible for the pathology report. RD and FC supervised SCCs, and one with unspecified non-small-cell lung cancer) this report. All authors read and approved the final and cutaneous vasculitis [4]. Paraneoplastic purpura in our manuscript. patient is plausible. An infectious origin was excluded based on clinical improvement with corticosteroids alone. Other Acknowledgments possible triggering factors were also excluded (medication, allergic reaction, and another autoimmune disease) )e authors thank Ms. Janet Jacobson for editorial (Table 1). assistance. Autoimmune paraneoplastic manifestations raise doubt as to the indication of immunotherapy for advanced or References locally advanced non-small-cell lung cancer. )e beneficial impacts of immunotherapy on overall survival and pro- [1] J. M. Zurada, K. M. Ward, and M. E. Grossman, “Henoch- gression-free survival are known [5–7], but patients with Schonlein ¨ purpura associated with malignancy in adults,” 4 Case Reports in Immunology Journalofthe AmericanAcademyofDermatology, vol. 55, no. 5, pp. S65–S70, 2006. [2] J. M. Greer, S. Longley, N. L. Edwards, G. J. Elfenbein, and R. S. Panush, “Vasculitis associated with malignancy experi- ence with 13 patients and literature review,” Medicine, vol. 67, no. 4, pp. 220–230, 1988. [3] R. Blanco, M. A. Gonzalez-Gay, ´ D. Ibañez, ´ C. Alba, and L. A. P´erez De Llano, “Henoch–Schonlein ¨ purpura as a clinical presentation of small cell lung cancer,” Clinical and Experi- mental Rheumatology, vol. 15, no. 5, pp. 545–547, 1997. [4] S. Holbrechts, J. Gorham, S. Sideris et al., “Autoimmune paraneoplastic syndromes associated to lung cancer: a sys- tematic review of the literature,” Lung Cancer, vol. 106, pp. 93–101, 2017. [5] S. J. Antonia, A. Villegas, D. Daniel et al., “Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC,” New England Journal of Medicine, vol. 379, no. 24, pp. 2342– 2350, 2018. [6] M. Reck, D. Rodr´ıguez-Abreu, A. G. Robinson et al., “Pem- brolizumab versus chemotherapy for PD-L1-positive non- small-cell lung cancer,” New England Journal of Medicine, vol. 375, no. 19, pp. 1823–1833, 2016. [7] L. Horn, D. R. Spigel, E. E. Vokes et al., “Nivolumab versus docetaxel in previously treated patients with advanced non- small-cell lung cancer: two-year outcomes from two ran- domized, open-label, phase III trials (CheckMate 017 and CheckMate 057),” Journal of Clinical Oncology, vol. 35, no. 35, pp. 3924–3933, 2017. [8] K. C. Arbour, L. Mezquita, N. Long et al., “Impact of baseline steroids on efficacy of programmed cell death-1 and pro- grammed death-ligand 1 blockade in patients with non-small- cell lung cancer,” Journal of Clinical Oncology, vol. 36, no. 28, pp. 2872–2878, 2018. [9] A. Tison, G. Quer ´ e, ´ L. Misery et al., “Safety and efficacy of immune checkpoint inhibitors in patients with cancer and preexisting autoimmune disease: a nationwide, multicenter cohort study,” Arthritis & Rheumatology, vol. 71, no. 12, pp. 2100–2111, 2019.

Journal

Case Reports in ImmunologyHindawi Publishing Corporation

Published: Feb 8, 2021

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