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Juvenile Dermatomyositis–Associated Panniculitis
To the Editor:
Juvenile dermatomyositis (JDM) is an autoimmune disorder with childhood onset that predominantly affects the muscles and skin, among other organs. Since the recognition of dermatomyositis (DM) more than 100 years ago, a variety of clinical diagnostic criteria have been utilized. Classically, DM presents with muscle weakness and a pathognomonic cutaneous macular, violaceous, erythematous eruption. The juvenile variant is defined by onset prior to 16 years of age. Histologically, these entities are indistinguishable and demonstrate an interface dermatitis with epidermal atrophy. Clinically, JDM has a higher incidence of calcinosis cutis and is not associated with an increased risk for malignancy in contrast to the adult-onset variant.1 Panniculitis is a rare but serious complication in a subset of patients with DM and may represent a precursor to calcinosis cutis.2 We describe a case of JDM-associated panniculitis that was difficult to control with prednisone and rituximab.
A 21-year-old woman with fever, fatigue, muscle pain, and new-onset swelling of 2 weeks’ duration was admitted to the hospital. She had a 5-year history of intermittent muscle weakness and concomitant rash. Prior to presentation, she had been hospitalized twice for fever of unknown origin, and the source remained undetermined. Physical examination revealed prominent facial and periorbital edema. There was tender nonpitting edema present on all 4 extremities and hyperpigmented indurated nodules on the shins (Figure 1). A full laboratory and imaging workup was performed for autoantibodies and infectious etiologies. The complete blood cell count was notable for pancytopenia, and a thorough infectious workup was negative. Creatine kinase level was within reference range. A biopsy of the right shin was performed, and histopathology revealed a lobular panniculitis with fat necrosis and mixed inflammation with neutrophils with perieccrine involvement as well as an interface dermatitis (Figure 2). Periodic acid–Schiff, Grocott methenamine-silver, and Gram stains were negative. Myositis-specific antibody testing revealed anti-p155/140 autoantibodies, and magnetic resonance imaging did not reveal active myositis within the visualized muscles, consistent with stable nonprogressing DM. A diagnosis of JDM with panniculitis was made. The patient was started on oral prednisone. Subsequently, a trial of rituximab was initiated. Although the patient’s symptoms initially improved, the response was not sustained on rituximab, and the patient was continued on systemic steroids with initiation of cyclosporine.
Juvenile dermatomyositis is an autoimmune disorder with childhood onset that involves systemic inflammation of the muscles, skin, and internal organs. It often can present diagnostic and therapeutic challenges.2,3 Bohan and Peter4,5 clinical criteria may help identify potential patients with JDM, but magnetic resonance imaging, electromyography, and muscle biopsy often are required to confirm the diagnosis.6 Skin manifestations include heliotrope rash; V sign; shawl sign; Gottron papules; periorbital edema; and infrequently panniculitis, the subcutaneous inflammation of adipose tissue.3,7
Although panniculitis is found in approximately 10% of skin biopsies in patients with DM, our patient presented with anti-p155/140 antibodies.8-10 Fat involvement in these patients traditionally manifests as lipodystrophy. Panniculitis also may precede calcinosis cutis, a debilitating skin change that may occur in approximately 46% of patients with JDM and can cause severe morbidity.2,6,9
Subcutaneous edema rarely is described in DM-panniculitis, present in only 6% of 86 DM patients in one study.7 The pathophysiology of DM may be due to antibodies that target endothelial cells and activate complement, resulting in the membranolytic attack complex. This leads to microischemia, and microinfarction of the muscle fibers has been suggested to result in edema of the subcutaneous tissue in severe cases.7,11 Microinfarction has been found to be present 2.3 times more often in edematous DM compared with nonedematous DM.7 Subcutaneous edema may be an isolated presentation of DM that arises more quickly with severe disease activity. As such, recommendations have been made to consider edema in future classification schemes.7
Because of the severity of edematous and/or subcutaneous DM, aggressive therapy may be required. First-line therapy consists of corticosteroids with additional immunosuppressants and immunomodulatory agents if adequate response is not achieved.3,12 The effectiveness of rituximab in DM has been suggested.2,12,13 The Rituximab in Myositis (RIM) trial (N=200) was the first double-blind, placebo-controlled, phase 3 clinical trial to assess rituximab’s efficacy in refractory compared with early-onset inflammatory myopathies. Although outcomes were similar in both groups, 83% of patients overall, including the JDM subset, met the definition of improvement.12 In re-examining the RIM trial data and other cases using rituximab to treat inflammatory myopathies, an overall response rate of 78.3% was observed, with 52.1% of patients with DM reporting improvement in skin lesions (N=458, pooled from 48 studies).13 Further analysis of the RIM data revealed that panniculitis affected 10.4% of patients with JDM at baseline, which decreased to 6.8% at 36 weeks of rituximab therapy (N=48).12
As exhibited in our patient, subcutaneous tissue involvement, including calcinosis cutis and panniculitis, is seen more often in JDM than adult DM.2,6 However, panniculitis in anti-p155/140 patients is rare. Our patient also had antibody positivity, which likely predisposed her to a more severe course. Despite not having sustained improvement on rituximab, initiating aggressive therapy earlier in the disease course may be beneficial, and our patient continues with alternative therapies.
- Jorizzo JL, Vleugels RA. Dermatomyositis. In: Bolognia J, Schaffer J, Cerroni L. Dermatology. 4th ed. Elsevier; 2019:681-687.
- Aggarwal R, Loganathan P, Koontz D, et al. Cutaneous improvement in refractory adult and juvenile dermatomyositis after treatment with rituximab. Rheumatology. 2016;56:247-254.
- Santos-Briz A, Calle A, Linos K, et al. Dermatomyositis panniculitis: a clinicopathological and immunohistochemical study of 18 cases. J Eur Acad Dermatol Venereol. 2018;32:1352-1359.
- Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292:344-347.
- Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975;292:403-407.
- Sakurai N, Hino-Shishikura A, Nozawa T, et al. Clinical significance of subcutaneous fat and fascial involvement in juvenile dermatomyositis. Mod Rheumatol. 2019;29:808-813.
- Milisenda JC, Doti PI, Prieto-Gonzalez S, et al. Dermatomyositis presenting with severe subcutaneous edema: five additional cases and review of the literature. Semin Arthritis Rheum. 2014;44:228-233.
- Janis JF, Winkelmann RK. Histopathology of the skin in dermatomyositis: a histopathologic study of 55 cases. Arch Dermatol. 1968;97:640-650.
- van Dongen HM, van Vugt RM, Stoof TJ. Extensive persistent panniculitis in the context of dermatomyositis. J Clin Rheumatol. 2020;26:e187-e188.
- Gunawardena H, Wedderburn LR, North J, et al. Clinical associations of autoantibodies to a p155/140 kDa doublet protein in juvenile dermatomyositis. Rheumatology. 2008;47:324-328.
- Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet. 2003;362:971-982.
- Oddis CV, Reed AM, Aggarwal R, et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013;65:314-324.
- Fasano S, Gordon P, Hajji R, et al. Rituximab in the treatment of inflammatory myopathies: a review. Rheumatology. 2016;56:26-36.
To the Editor:
Juvenile dermatomyositis (JDM) is an autoimmune disorder with childhood onset that predominantly affects the muscles and skin, among other organs. Since the recognition of dermatomyositis (DM) more than 100 years ago, a variety of clinical diagnostic criteria have been utilized. Classically, DM presents with muscle weakness and a pathognomonic cutaneous macular, violaceous, erythematous eruption. The juvenile variant is defined by onset prior to 16 years of age. Histologically, these entities are indistinguishable and demonstrate an interface dermatitis with epidermal atrophy. Clinically, JDM has a higher incidence of calcinosis cutis and is not associated with an increased risk for malignancy in contrast to the adult-onset variant.1 Panniculitis is a rare but serious complication in a subset of patients with DM and may represent a precursor to calcinosis cutis.2 We describe a case of JDM-associated panniculitis that was difficult to control with prednisone and rituximab.
A 21-year-old woman with fever, fatigue, muscle pain, and new-onset swelling of 2 weeks’ duration was admitted to the hospital. She had a 5-year history of intermittent muscle weakness and concomitant rash. Prior to presentation, she had been hospitalized twice for fever of unknown origin, and the source remained undetermined. Physical examination revealed prominent facial and periorbital edema. There was tender nonpitting edema present on all 4 extremities and hyperpigmented indurated nodules on the shins (Figure 1). A full laboratory and imaging workup was performed for autoantibodies and infectious etiologies. The complete blood cell count was notable for pancytopenia, and a thorough infectious workup was negative. Creatine kinase level was within reference range. A biopsy of the right shin was performed, and histopathology revealed a lobular panniculitis with fat necrosis and mixed inflammation with neutrophils with perieccrine involvement as well as an interface dermatitis (Figure 2). Periodic acid–Schiff, Grocott methenamine-silver, and Gram stains were negative. Myositis-specific antibody testing revealed anti-p155/140 autoantibodies, and magnetic resonance imaging did not reveal active myositis within the visualized muscles, consistent with stable nonprogressing DM. A diagnosis of JDM with panniculitis was made. The patient was started on oral prednisone. Subsequently, a trial of rituximab was initiated. Although the patient’s symptoms initially improved, the response was not sustained on rituximab, and the patient was continued on systemic steroids with initiation of cyclosporine.
Juvenile dermatomyositis is an autoimmune disorder with childhood onset that involves systemic inflammation of the muscles, skin, and internal organs. It often can present diagnostic and therapeutic challenges.2,3 Bohan and Peter4,5 clinical criteria may help identify potential patients with JDM, but magnetic resonance imaging, electromyography, and muscle biopsy often are required to confirm the diagnosis.6 Skin manifestations include heliotrope rash; V sign; shawl sign; Gottron papules; periorbital edema; and infrequently panniculitis, the subcutaneous inflammation of adipose tissue.3,7
Although panniculitis is found in approximately 10% of skin biopsies in patients with DM, our patient presented with anti-p155/140 antibodies.8-10 Fat involvement in these patients traditionally manifests as lipodystrophy. Panniculitis also may precede calcinosis cutis, a debilitating skin change that may occur in approximately 46% of patients with JDM and can cause severe morbidity.2,6,9
Subcutaneous edema rarely is described in DM-panniculitis, present in only 6% of 86 DM patients in one study.7 The pathophysiology of DM may be due to antibodies that target endothelial cells and activate complement, resulting in the membranolytic attack complex. This leads to microischemia, and microinfarction of the muscle fibers has been suggested to result in edema of the subcutaneous tissue in severe cases.7,11 Microinfarction has been found to be present 2.3 times more often in edematous DM compared with nonedematous DM.7 Subcutaneous edema may be an isolated presentation of DM that arises more quickly with severe disease activity. As such, recommendations have been made to consider edema in future classification schemes.7
Because of the severity of edematous and/or subcutaneous DM, aggressive therapy may be required. First-line therapy consists of corticosteroids with additional immunosuppressants and immunomodulatory agents if adequate response is not achieved.3,12 The effectiveness of rituximab in DM has been suggested.2,12,13 The Rituximab in Myositis (RIM) trial (N=200) was the first double-blind, placebo-controlled, phase 3 clinical trial to assess rituximab’s efficacy in refractory compared with early-onset inflammatory myopathies. Although outcomes were similar in both groups, 83% of patients overall, including the JDM subset, met the definition of improvement.12 In re-examining the RIM trial data and other cases using rituximab to treat inflammatory myopathies, an overall response rate of 78.3% was observed, with 52.1% of patients with DM reporting improvement in skin lesions (N=458, pooled from 48 studies).13 Further analysis of the RIM data revealed that panniculitis affected 10.4% of patients with JDM at baseline, which decreased to 6.8% at 36 weeks of rituximab therapy (N=48).12
As exhibited in our patient, subcutaneous tissue involvement, including calcinosis cutis and panniculitis, is seen more often in JDM than adult DM.2,6 However, panniculitis in anti-p155/140 patients is rare. Our patient also had antibody positivity, which likely predisposed her to a more severe course. Despite not having sustained improvement on rituximab, initiating aggressive therapy earlier in the disease course may be beneficial, and our patient continues with alternative therapies.
To the Editor:
Juvenile dermatomyositis (JDM) is an autoimmune disorder with childhood onset that predominantly affects the muscles and skin, among other organs. Since the recognition of dermatomyositis (DM) more than 100 years ago, a variety of clinical diagnostic criteria have been utilized. Classically, DM presents with muscle weakness and a pathognomonic cutaneous macular, violaceous, erythematous eruption. The juvenile variant is defined by onset prior to 16 years of age. Histologically, these entities are indistinguishable and demonstrate an interface dermatitis with epidermal atrophy. Clinically, JDM has a higher incidence of calcinosis cutis and is not associated with an increased risk for malignancy in contrast to the adult-onset variant.1 Panniculitis is a rare but serious complication in a subset of patients with DM and may represent a precursor to calcinosis cutis.2 We describe a case of JDM-associated panniculitis that was difficult to control with prednisone and rituximab.
A 21-year-old woman with fever, fatigue, muscle pain, and new-onset swelling of 2 weeks’ duration was admitted to the hospital. She had a 5-year history of intermittent muscle weakness and concomitant rash. Prior to presentation, she had been hospitalized twice for fever of unknown origin, and the source remained undetermined. Physical examination revealed prominent facial and periorbital edema. There was tender nonpitting edema present on all 4 extremities and hyperpigmented indurated nodules on the shins (Figure 1). A full laboratory and imaging workup was performed for autoantibodies and infectious etiologies. The complete blood cell count was notable for pancytopenia, and a thorough infectious workup was negative. Creatine kinase level was within reference range. A biopsy of the right shin was performed, and histopathology revealed a lobular panniculitis with fat necrosis and mixed inflammation with neutrophils with perieccrine involvement as well as an interface dermatitis (Figure 2). Periodic acid–Schiff, Grocott methenamine-silver, and Gram stains were negative. Myositis-specific antibody testing revealed anti-p155/140 autoantibodies, and magnetic resonance imaging did not reveal active myositis within the visualized muscles, consistent with stable nonprogressing DM. A diagnosis of JDM with panniculitis was made. The patient was started on oral prednisone. Subsequently, a trial of rituximab was initiated. Although the patient’s symptoms initially improved, the response was not sustained on rituximab, and the patient was continued on systemic steroids with initiation of cyclosporine.
Juvenile dermatomyositis is an autoimmune disorder with childhood onset that involves systemic inflammation of the muscles, skin, and internal organs. It often can present diagnostic and therapeutic challenges.2,3 Bohan and Peter4,5 clinical criteria may help identify potential patients with JDM, but magnetic resonance imaging, electromyography, and muscle biopsy often are required to confirm the diagnosis.6 Skin manifestations include heliotrope rash; V sign; shawl sign; Gottron papules; periorbital edema; and infrequently panniculitis, the subcutaneous inflammation of adipose tissue.3,7
Although panniculitis is found in approximately 10% of skin biopsies in patients with DM, our patient presented with anti-p155/140 antibodies.8-10 Fat involvement in these patients traditionally manifests as lipodystrophy. Panniculitis also may precede calcinosis cutis, a debilitating skin change that may occur in approximately 46% of patients with JDM and can cause severe morbidity.2,6,9
Subcutaneous edema rarely is described in DM-panniculitis, present in only 6% of 86 DM patients in one study.7 The pathophysiology of DM may be due to antibodies that target endothelial cells and activate complement, resulting in the membranolytic attack complex. This leads to microischemia, and microinfarction of the muscle fibers has been suggested to result in edema of the subcutaneous tissue in severe cases.7,11 Microinfarction has been found to be present 2.3 times more often in edematous DM compared with nonedematous DM.7 Subcutaneous edema may be an isolated presentation of DM that arises more quickly with severe disease activity. As such, recommendations have been made to consider edema in future classification schemes.7
Because of the severity of edematous and/or subcutaneous DM, aggressive therapy may be required. First-line therapy consists of corticosteroids with additional immunosuppressants and immunomodulatory agents if adequate response is not achieved.3,12 The effectiveness of rituximab in DM has been suggested.2,12,13 The Rituximab in Myositis (RIM) trial (N=200) was the first double-blind, placebo-controlled, phase 3 clinical trial to assess rituximab’s efficacy in refractory compared with early-onset inflammatory myopathies. Although outcomes were similar in both groups, 83% of patients overall, including the JDM subset, met the definition of improvement.12 In re-examining the RIM trial data and other cases using rituximab to treat inflammatory myopathies, an overall response rate of 78.3% was observed, with 52.1% of patients with DM reporting improvement in skin lesions (N=458, pooled from 48 studies).13 Further analysis of the RIM data revealed that panniculitis affected 10.4% of patients with JDM at baseline, which decreased to 6.8% at 36 weeks of rituximab therapy (N=48).12
As exhibited in our patient, subcutaneous tissue involvement, including calcinosis cutis and panniculitis, is seen more often in JDM than adult DM.2,6 However, panniculitis in anti-p155/140 patients is rare. Our patient also had antibody positivity, which likely predisposed her to a more severe course. Despite not having sustained improvement on rituximab, initiating aggressive therapy earlier in the disease course may be beneficial, and our patient continues with alternative therapies.
- Jorizzo JL, Vleugels RA. Dermatomyositis. In: Bolognia J, Schaffer J, Cerroni L. Dermatology. 4th ed. Elsevier; 2019:681-687.
- Aggarwal R, Loganathan P, Koontz D, et al. Cutaneous improvement in refractory adult and juvenile dermatomyositis after treatment with rituximab. Rheumatology. 2016;56:247-254.
- Santos-Briz A, Calle A, Linos K, et al. Dermatomyositis panniculitis: a clinicopathological and immunohistochemical study of 18 cases. J Eur Acad Dermatol Venereol. 2018;32:1352-1359.
- Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292:344-347.
- Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975;292:403-407.
- Sakurai N, Hino-Shishikura A, Nozawa T, et al. Clinical significance of subcutaneous fat and fascial involvement in juvenile dermatomyositis. Mod Rheumatol. 2019;29:808-813.
- Milisenda JC, Doti PI, Prieto-Gonzalez S, et al. Dermatomyositis presenting with severe subcutaneous edema: five additional cases and review of the literature. Semin Arthritis Rheum. 2014;44:228-233.
- Janis JF, Winkelmann RK. Histopathology of the skin in dermatomyositis: a histopathologic study of 55 cases. Arch Dermatol. 1968;97:640-650.
- van Dongen HM, van Vugt RM, Stoof TJ. Extensive persistent panniculitis in the context of dermatomyositis. J Clin Rheumatol. 2020;26:e187-e188.
- Gunawardena H, Wedderburn LR, North J, et al. Clinical associations of autoantibodies to a p155/140 kDa doublet protein in juvenile dermatomyositis. Rheumatology. 2008;47:324-328.
- Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet. 2003;362:971-982.
- Oddis CV, Reed AM, Aggarwal R, et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013;65:314-324.
- Fasano S, Gordon P, Hajji R, et al. Rituximab in the treatment of inflammatory myopathies: a review. Rheumatology. 2016;56:26-36.
- Jorizzo JL, Vleugels RA. Dermatomyositis. In: Bolognia J, Schaffer J, Cerroni L. Dermatology. 4th ed. Elsevier; 2019:681-687.
- Aggarwal R, Loganathan P, Koontz D, et al. Cutaneous improvement in refractory adult and juvenile dermatomyositis after treatment with rituximab. Rheumatology. 2016;56:247-254.
- Santos-Briz A, Calle A, Linos K, et al. Dermatomyositis panniculitis: a clinicopathological and immunohistochemical study of 18 cases. J Eur Acad Dermatol Venereol. 2018;32:1352-1359.
- Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292:344-347.
- Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975;292:403-407.
- Sakurai N, Hino-Shishikura A, Nozawa T, et al. Clinical significance of subcutaneous fat and fascial involvement in juvenile dermatomyositis. Mod Rheumatol. 2019;29:808-813.
- Milisenda JC, Doti PI, Prieto-Gonzalez S, et al. Dermatomyositis presenting with severe subcutaneous edema: five additional cases and review of the literature. Semin Arthritis Rheum. 2014;44:228-233.
- Janis JF, Winkelmann RK. Histopathology of the skin in dermatomyositis: a histopathologic study of 55 cases. Arch Dermatol. 1968;97:640-650.
- van Dongen HM, van Vugt RM, Stoof TJ. Extensive persistent panniculitis in the context of dermatomyositis. J Clin Rheumatol. 2020;26:e187-e188.
- Gunawardena H, Wedderburn LR, North J, et al. Clinical associations of autoantibodies to a p155/140 kDa doublet protein in juvenile dermatomyositis. Rheumatology. 2008;47:324-328.
- Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet. 2003;362:971-982.
- Oddis CV, Reed AM, Aggarwal R, et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013;65:314-324.
- Fasano S, Gordon P, Hajji R, et al. Rituximab in the treatment of inflammatory myopathies: a review. Rheumatology. 2016;56:26-36.
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Sable, MD; David Rosenfeld, MD; Jodi Speiser, MD</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange>E8-E10</pageRange> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:"> <name/> <rightsInfo> <copyrightHolder> <name/> </copyrightHolder> <copyrightNotice/> </rightsInfo> </provider> <abstract/> <metaDescription>To the Editor:Juvenile dermatomyositis (JDM) is an autoimmune disorder with childhood onset that predominantly affects the muscles and skin, among other organs.</metaDescription> <articlePDF>291862</articlePDF> <teaserImage/> <title>Juvenile Dermatomyositis–Associated Panniculitis</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear>2022</pubPubdateYear> <pubPubdateMonth>December</pubPubdateMonth> <pubPubdateDay/> <pubVolume>110</pubVolume> <pubNumber>6</pubNumber> <wireChannels/> <primaryCMSID/> <CMSIDs> <CMSID>2165</CMSID> </CMSIDs> <keywords> <keyword>pediatrics</keyword> <keyword> autoimmune disease</keyword> <keyword> juvenile dermatomyositis-associated panniculitis</keyword> </keywords> <seeAlsos/> <publications_g> <publicationData> <publicationCode>CT</publicationCode> <pubIssueName>December 2022</pubIssueName> <pubArticleType>Audio | 2165</pubArticleType> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle>Cutis</journalTitle> <journalFullTitle>Cutis</journalFullTitle> <copyrightStatement>Copyright 2015 Frontline Medical Communications Inc., Parsippany, NJ, USA. All rights reserved.</copyrightStatement> </publicationData> </publications_g> <publications> <term canonical="true">12</term> </publications> <sections> <term canonical="true">44</term> </sections> <topics> <term>271</term> <term canonical="true">29134</term> </topics> <links> <link> <itemClass qcode="ninat:composite"/> <altRep contenttype="application/pdf">images/18002304.pdf</altRep> <description role="drol:caption"/> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Juvenile Dermatomyositis–Associated Panniculitis</title> <deck/> </itemMeta> <itemContent> <p>To the Editor:<br/><br/>Juvenile dermatomyositis (JDM) is an autoimmune disorder with childhood onset that predominantly affects the muscles and skin, among other organs. Since the recognition of dermatomyositis (DM) more than 100 years ago, a variety of clinical diagnostic criteria have been utilized. Classically, DM presents with muscle weakness and a pathognomonic cutaneous macular, violaceous, erythematous eruption. The juvenile variant is defined by onset prior to 16 years of age. Histologically, these entities are indistinguishable and demonstrate an interface dermatitis with epidermal atrophy. Clinically, JDM has a higher incidence of calcinosis cutis and is not associated with an increased risk for malignancy in contrast to the adult-onset variant.<sup>1</sup> Panniculitis is a rare but serious complication in a subset of patients with DM and may represent a precursor to calcinosis cutis.<sup>2</sup> We describe a case of JDM-associated panniculitis that was difficult to control with prednisone and rituximab. </p> <p>A 21-year-old woman<b> </b>with fever, fatigue, muscle pain, and new-onset swelling of 2 weeks’ duration was admitted to the hospital. She had a 5-year history of intermittent muscle weakness and concomitant rash. Prior to presentation, she had been hospitalized twice for fever of unknown origin, and the source remained undetermined. Physical examination revealed prominent facial and periorbital edema. There was tender nonpitting edema present on all 4 extremities and hyperpigmented indurated nodules on the shins (Figure 1). A full laboratory and imaging workup was performed for autoantibodies and infectious etiologies. The complete blood cell count was notable for pancytopenia, and a thorough infectious workup was negative. Creatine kinase level was within reference range. A biopsy of the right shin was performed, and histopathology revealed a lobular panniculitis with fat necrosis and mixed inflammation with neutrophils with perieccrine involvement as well as an interface dermatitis (Figure 2). Periodic acid–Schiff, Grocott methenamine-silver, and Gram stains were negative. Myositis-specific antibody testing revealed anti-p155/140 autoantibodies, and magnetic resonance imaging did not reveal active myositis within the visualized muscles, consistent with stable nonprogressing DM. A diagnosis of JDM with panniculitis was made. The patient was started on oral prednisone. Subsequently, a trial of rituximab was initiated. Although the patient’s symptoms initially improved, the response was not sustained on rituximab, and the patient was continued on systemic steroids with initiation of cyclosporine.<br/><br/>Juvenile dermatomyositis is an autoimmune disorder with childhood onset that involves systemic inflammation of the muscles, skin, and internal organs. It often can present diagnostic and therapeutic challenges.<sup>2,3</sup> Bohan and Peter<sup>4,5</sup> clinical criteria may help identify potential patients with JDM, but magnetic resonance imaging, electromyography, and muscle biopsy often are required to confirm the diagnosis.<sup>6</sup> Skin manifestations include heliotrope rash; <i>V</i> sign; shawl sign; Gottron papules; periorbital edema; and infrequently panniculitis, the subcutaneous inflammation of adipose tissue.<sup>3,7</sup> <br/><br/>Although panniculitis is found in approximately 10% of skin biopsies in patients with DM, our patient presented with anti-p155/140 antibodies.<sup>8-10</sup><b> </b>Fat involvement in these patients traditionally manifests as lipodystrophy. Panniculitis also may precede calcinosis cutis, a debilitating skin change that may occur in approximately 46% of patients with JDM and can cause severe morbidity.<sup>2,6,9<br/><br/></sup>Subcutaneous edema rarely is described in DM-panniculitis, present in only 6% of 86 DM<b> </b>patients in one study.<sup>7</sup> The pathophysiology of DM may be due to antibodies that target endothelial cells and activate complement, resulting in the membranolytic attack complex. This leads to microischemia, and microinfarction of the muscle fibers has been suggested to result in edema of the subcutaneous tissue in severe cases.<sup>7,11</sup> Microinfarction has been found to be present 2.3 times more often in edematous DM compared with nonedematous DM.<sup>7</sup> Subcutaneous edema may be an isolated presentation of DM that arises more quickly with severe disease activity. As such, recommendations have been made to consider edema in future classification schemes.<sup>7</sup> <br/><br/>Because of the severity of edematous and/or subcutaneous DM, aggressive therapy may be required. First-line therapy consists of corticosteroids with additional immunosuppressants and immunomodulatory agents if adequate response is not achieved.<sup>3,12</sup> The effectiveness of rituximab in DM has been suggested.<sup>2,12,13</sup> The Rituximab in Myositis (RIM) trial (N<span class="body">=</span>200) was the first double-blind, placebo-controlled, phase 3 clinical trial to assess rituximab’s efficacy in refractory compared with early-onset inflammatory myopathies. Although outcomes were similar in both groups, 83% of patients overall, including the JDM subset, met the definition of improvement.<sup>12</sup> In re-examining the RIM trial data and other cases using rituximab to treat inflammatory myopathies, an overall response rate of 78.3% was observed, with 52.1% of patients with DM reporting improvement in skin lesions (N<span class="body">=</span>458, pooled from 48 studies).<sup>13</sup> Further analysis of the RIM data revealed that panniculitis affected 10.4% of patients with JDM at baseline, which decreased to 6.8% at 36 weeks of rituximab therapy (N<span class="body">=</span>48).<sup>12<br/><br/></sup>As exhibited in our patient, subcutaneous tissue involvement, including calcinosis cutis and panniculitis, is seen more often in JDM than adult DM.<sup>2,6</sup> However, panniculitis in anti-p155/140 patients is rare. Our patient also had antibody positivity, which likely predisposed her to a more severe course. Despite not having sustained improvement on rituximab, initiating aggressive therapy earlier in the disease course may be beneficial, and our patient continues with alternative therapies. </p> <h2>References </h2> <p class="reference"> 1. Jorizzo JL, Vleugels RA. Dermatomyositis. In: Bolognia J, Schaffer J, Cerroni L. <i>Dermatology</i>.<i> </i>4th ed. Elsevier; 2019:681-687.</p> <p class="reference"> 2. Aggarwal R, Loganathan P, Koontz D, et al. Cutaneous improvement in refractory adult and juvenile dermatomyositis after treatment with rituximab. <i>Rheumatology</i>. 2016;56:247-254.<br/><br/> 3. Santos-Briz A, Calle A, Linos K, et al. Dermatomyositis panniculitis: a clinicopathological and immunohistochemical study of 18 cases.<span class="apple-converted-space"> </span><i>J Eur Acad Dermatol Venereol.</i> 2018;32:1352-1359. <br/><br/> 4. Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). <i>N Engl J Med</i>. 1975;292:344-347. 5. Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). <i>N Engl J Med. </i>1975;292:403-407.<br/><br/> 6. Sakurai N, Hino-Shishikura A, Nozawa T, et al. Clinical significance of subcutaneous fat and fascial involvement in juvenile dermatomyositis. <i>Mod Rheumatol</i>. 2019;29:808-813.<br/><br/> 7. Milisenda JC, Doti PI, Prieto-Gonzalez S, et al. Dermatomyositis presenting with severe subcutaneous edema: five additional cases and review of the literature.<span class="apple-converted-space"> </span><i>Semin Arthritis Rheum</i>. 2014;44:228-233.<br/><br/> 8. Janis JF, Winkelmann RK. Histopathology of the skin in dermatomyositis<span class="colon-for-citation-subtitle">:</span><span class="apple-converted-space"> </span><span class="subtitle1">a histopathologic study of 55 cases</span>.<span class="apple-converted-space"> </span><span class="Emphasis">Arch Dermatol.</span><span class="apple-converted-space"> </span>1968;97:640-650. <br/><br/> 9. van Dongen HM, van Vugt RM, Stoof TJ. Extensive persistent panniculitis in the context of dermatomyositis. <i>J Clin Rheumatol. </i>2020;26:e187-e188.<br/><br/>10. Gunawardena H, Wedderburn LR, North J, et al. Clinical associations of autoantibodies to a p155/140 kDa doublet protein in juvenile dermatomyositis.<span class="apple-converted-space"> </span><i>Rheumatology.</i> 2008;47:324-328. <br/><br/>11. Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. <i>Lancet</i>. 2003;362:971-982. <br/><br/>12. Oddis CV, Reed AM, Aggarwal R, et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial.<span class="apple-converted-space"> </span><i>Arthritis Rheum</i>. 2013;65:314-324. <br/><br/>13. Fasano S, Gordon P, Hajji R, et al. Rituximab in the treatment of inflammatory myopathies: a review. <i>Rheumatology.</i> 2016;56:26-36. </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>bio</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p class="disclosure">Dr. Sable is from the Department of Dermatology, University of Wisconsin, Madison. Drs. Rosenfeld, Speiser, and Lake are from the Loyola University Medical Center, Maywood, Illinois. Drs. Rosenfeld and Lake are from the Division of Dermatology, and Dr. Speiser is from the Department of Pathology and Laboratory Medicine. </p> <p class="disclosure">The authors report no conflict of interest. <br/><br/>Correspondence: Eden Lake, MD, Division of Dermatology, Loyola University Medical Center, 2160 S First St, Maywood, IL 60153 (eden.lake@lumc.edu).<br/><br/>doi:10.12788/cutis.0675</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>in</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p class="insidehead">Practice <strong>Points</strong></p> <ul class="insidebody"> <li>Juvenile dermatomyositis is an autoimmune disorder with childhood onset that predominantly affects the muscles and skin. </li> <li>Juvenile dermatomyositis has a higher incidence of calcinosis cutis and is not associated with an increased risk for malignancy in contrast to the adult-onset variant, dermatomyositis (DM). </li> <li>Panniculitis is a rare but severe complication of DM, and this subset of DM may be challenging to treat, requiring aggressive therapy.</li> </ul> </itemContent> </newsItem> </itemSet></root>
Practice Points
- Juvenile dermatomyositis is an autoimmune disorder with childhood onset that predominantly affects the muscles and skin.
- Juvenile dermatomyositis has a higher incidence of calcinosis cutis and is not associated with an increased risk for malignancy in contrast to the adult-onset variant, dermatomyositis (DM).
- Panniculitis is a rare but severe complication of DM, and this subset of DM may be challenging to treat, requiring aggressive therapy.
Reactivation of a BCG Vaccination Scar Following the First Dose of the Moderna COVID-19 Vaccine
The COVID-19 pandemic has resulted in notable morbidity and mortality worldwide. In December 2020, the US Food and Drug Administration issued an Emergency Use Authorization for 2 messenger RNA (mRNA) vaccines—produced by Pfizer-BioNTech and Moderna—for the prevention of COVID-19. Phase 3 trials of the vaccine developed by Moderna showed 94.1% efficacy at preventing COVID-19 after 2 doses.1
Common cutaneous adverse effects of the Moderna COVID-19 Vaccine include injection-site reactions, such as pain, induration, and erythema. Less frequently reported dermatologic adverse effects include diffuse bullous rash and hypersensitivity reactions.1 We report a case of reactivation of a BCG vaccination scar after the first dose of the Moderna COVID-19 Vaccine.
Case Report
A 48-year-old Asian man who was otherwise healthy presented with erythema, induration, and mild pruritus on the deltoid muscle of the left arm, near the scar from an earlier BCG vaccine, which he received at approximately 5 years of age when living in Taiwan. The patient received the first dose of the Moderna COVID-19 Vaccine approximately 5 to 7 cm distant from the BCG vaccination scar. One to 2 days after inoculation, the patient endorsed tenderness at the site of COVID-19 vaccination but denied systemic symptoms. He had never been given a diagnosis of COVID-19. His SARS-CoV-2 antibody status was unknown.
Eight days later, the patient noticed a well-defined, erythematous, indurated plaque with mild itchiness overlying and around the BCG vaccination scar that did not involve the COVID-19 vaccination site. The following day, the redness and induration became worse (Figure).
The patient was otherwise well. Vital signs were normal; there was no lymphadenopathy. The rash resolved without treatment over the next 4 days.
Comment
The BCG vaccine is an intradermal live attenuated virus vaccine used to prevent certain forms of tuberculosis and potentially other Mycobacterium infections. Although the vaccine is not routinely administered in the United States, it is part of the vaccination schedule in most countries, administered most often to newborns and infants. Administration of the BCG vaccine commonly results in mild localized erythema, swelling, and pain at the injection site. Most inoculated patients also develop an ulcer that heals with the characteristic BCG vaccination scar.2,3
There is evidence that the BCG vaccine can enhance the innate immune system response and might decrease the rate of infection by unrelated pathogens, including viruses.4 Several epidemiologic studies have suggested that the BCG vaccine might offer some protection against COVID-19, possibly due to a resemblance of the amino acid sequences of BCG and SARS-CoV-2, which might provoke cross-reactive T cells.5,6 Further studies are underway to determine whether the BCG vaccine is truly protective against COVID-19.
BCG vaccination scar reactivation presents as redness, swelling, or ulceration at the BCG injection site months to years after inoculation. Although erythema and induration of the BCG scar are not included in the diagnostic criteria of Kawasaki disease, likely due to variable vaccine requirements in different countries, these findings are largely recognized as specific for Kawasaki disease and present in approximately half of affected patients who received the BCG vaccine.2
Heat Shock Proteins—Heat shock proteins (HSPs) are produced by cells in response to stressors. The proposed mechanism of BCG vaccination scar reactivation is a cross-reaction between human homologue HSP 63 and Mycobacterium HSP 65, leading to hyperactivity of the immune system against BCG.7 There also are reports of reactivation of a BCG vaccination scar from measles infection and influenza vaccination.2,8,9 Most prior reports of BCG vaccination scar reactivation have been in pediatric patients; our patient is an adult who received the BCG vaccine more than 40 years ago.
Mechanism of Reactivation—The mechanism of BCG vaccination scar reactivation in our patient, who received the Moderna COVID-19 Vaccine, is unclear. Possible mechanisms include (1) release of HSP mediated by the COVID-19 vaccine, leading to an immune response at the BCG vaccine scar, or (2) another immune-mediated cross-reaction between BCG and the Moderna COVID-19 Vaccine mRNA nanoparticle or encoded spike protein antigen. It has been hypothesized that the BCG vaccine might offer some protection against COVID-19; this remains uncertain and is under further investigation.10 A recent retrospective cohort study showed that a BCG vaccination booster may decrease COVID-19 infection rates in higher-risk populations.11
Conclusion
We present a case of BCG vaccine scar reactivation occurring after a dose of the Moderna COVID-19 Vaccine, a likely underreported, self-limiting, cutaneous adverse effect of this mRNA vaccine.
- Baden LR, El Sahly HM, Essink B, et al; COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2020;384:403-416. doi:10.1056/NEJMoa2035389
- Muthuvelu S, Lim KS, Huang L-Y, et al. Measles infection causing bacillus Calmette-Guérin reactivation: a case report. BMC Pediatr. 2019;19:251. doi:10.1186/s12887-019-1635-z
- Fatima S, Kumari A, Das G, et al. Tuberculosis vaccine: a journey from BCG to present. Life Sci. 2020;252:117594. doi:10.1016/j.lfs.2020.117594
- O’Neill LAJ, Netea MG. BCG-induced trained immunity: can it offer protection against COVID-19? Nat Rev Immunol. 2020;20:335-337. doi:10.1038/s41577-020-0337-y
- Brooks NA, Puri A, Garg S, et al. The association of coronavirus disease-19 mortality and prior bacille Calmette-Guérin vaccination: a robust ecological analysis using unsupervised machine learning. Sci Rep. 2021;11:774. doi:10.1038/s41598-020-80787-z
- Tomita Y, Sato R, Ikeda T, et al. BCG vaccine may generate cross-reactive T-cells against SARS-CoV-2: in silico analyses and a hypothesis. Vaccine. 2020;38:6352-6356. doi:10.1016/j.vaccine.2020.08.045
- Lim KYY, Chua MC, Tan NWH, et al. Reactivation of BCG inoculation site in a child with febrile exanthema of 3 days duration: an early indicator of incomplete Kawasaki disease. BMJ Case Rep. 2020;13:E239648. doi:10.1136/bcr-2020-239648
- Kondo M, Goto H, Yamamoto S. First case of redness and erosion at bacillus Calmette-Guérin inoculation site after vaccination against influenza. J Dermatol. 2016;43:1229-1231. doi:10.1111/1346-8138.13365
- Chavarri-Guerra Y, Soto-Pérez-de-Celis E. Erythema at the bacillus Calmette-Guerin scar after influenza vaccination. Rev Soc Bras Med Trop. 2019;53:E20190390. doi:10.1590/0037-8682-0390-2019
- Fu W, Ho P-C, Liu C-L, et al. Reconcile the debate over protective effects of BCG vaccine against COVID-19. Sci Rep. 2021;11:8356. doi:10.1038/s41598-021-87731-9
- Amirlak L, Haddad R, Hardy JD, et al. Effectiveness of booster BCG vaccination in preventing COVID-19 infection. Hum Vaccin Immunother. 2021;17:3913-3915. doi:10.1080/21645515.2021.1956228
The COVID-19 pandemic has resulted in notable morbidity and mortality worldwide. In December 2020, the US Food and Drug Administration issued an Emergency Use Authorization for 2 messenger RNA (mRNA) vaccines—produced by Pfizer-BioNTech and Moderna—for the prevention of COVID-19. Phase 3 trials of the vaccine developed by Moderna showed 94.1% efficacy at preventing COVID-19 after 2 doses.1
Common cutaneous adverse effects of the Moderna COVID-19 Vaccine include injection-site reactions, such as pain, induration, and erythema. Less frequently reported dermatologic adverse effects include diffuse bullous rash and hypersensitivity reactions.1 We report a case of reactivation of a BCG vaccination scar after the first dose of the Moderna COVID-19 Vaccine.
Case Report
A 48-year-old Asian man who was otherwise healthy presented with erythema, induration, and mild pruritus on the deltoid muscle of the left arm, near the scar from an earlier BCG vaccine, which he received at approximately 5 years of age when living in Taiwan. The patient received the first dose of the Moderna COVID-19 Vaccine approximately 5 to 7 cm distant from the BCG vaccination scar. One to 2 days after inoculation, the patient endorsed tenderness at the site of COVID-19 vaccination but denied systemic symptoms. He had never been given a diagnosis of COVID-19. His SARS-CoV-2 antibody status was unknown.
Eight days later, the patient noticed a well-defined, erythematous, indurated plaque with mild itchiness overlying and around the BCG vaccination scar that did not involve the COVID-19 vaccination site. The following day, the redness and induration became worse (Figure).
The patient was otherwise well. Vital signs were normal; there was no lymphadenopathy. The rash resolved without treatment over the next 4 days.
Comment
The BCG vaccine is an intradermal live attenuated virus vaccine used to prevent certain forms of tuberculosis and potentially other Mycobacterium infections. Although the vaccine is not routinely administered in the United States, it is part of the vaccination schedule in most countries, administered most often to newborns and infants. Administration of the BCG vaccine commonly results in mild localized erythema, swelling, and pain at the injection site. Most inoculated patients also develop an ulcer that heals with the characteristic BCG vaccination scar.2,3
There is evidence that the BCG vaccine can enhance the innate immune system response and might decrease the rate of infection by unrelated pathogens, including viruses.4 Several epidemiologic studies have suggested that the BCG vaccine might offer some protection against COVID-19, possibly due to a resemblance of the amino acid sequences of BCG and SARS-CoV-2, which might provoke cross-reactive T cells.5,6 Further studies are underway to determine whether the BCG vaccine is truly protective against COVID-19.
BCG vaccination scar reactivation presents as redness, swelling, or ulceration at the BCG injection site months to years after inoculation. Although erythema and induration of the BCG scar are not included in the diagnostic criteria of Kawasaki disease, likely due to variable vaccine requirements in different countries, these findings are largely recognized as specific for Kawasaki disease and present in approximately half of affected patients who received the BCG vaccine.2
Heat Shock Proteins—Heat shock proteins (HSPs) are produced by cells in response to stressors. The proposed mechanism of BCG vaccination scar reactivation is a cross-reaction between human homologue HSP 63 and Mycobacterium HSP 65, leading to hyperactivity of the immune system against BCG.7 There also are reports of reactivation of a BCG vaccination scar from measles infection and influenza vaccination.2,8,9 Most prior reports of BCG vaccination scar reactivation have been in pediatric patients; our patient is an adult who received the BCG vaccine more than 40 years ago.
Mechanism of Reactivation—The mechanism of BCG vaccination scar reactivation in our patient, who received the Moderna COVID-19 Vaccine, is unclear. Possible mechanisms include (1) release of HSP mediated by the COVID-19 vaccine, leading to an immune response at the BCG vaccine scar, or (2) another immune-mediated cross-reaction between BCG and the Moderna COVID-19 Vaccine mRNA nanoparticle or encoded spike protein antigen. It has been hypothesized that the BCG vaccine might offer some protection against COVID-19; this remains uncertain and is under further investigation.10 A recent retrospective cohort study showed that a BCG vaccination booster may decrease COVID-19 infection rates in higher-risk populations.11
Conclusion
We present a case of BCG vaccine scar reactivation occurring after a dose of the Moderna COVID-19 Vaccine, a likely underreported, self-limiting, cutaneous adverse effect of this mRNA vaccine.
The COVID-19 pandemic has resulted in notable morbidity and mortality worldwide. In December 2020, the US Food and Drug Administration issued an Emergency Use Authorization for 2 messenger RNA (mRNA) vaccines—produced by Pfizer-BioNTech and Moderna—for the prevention of COVID-19. Phase 3 trials of the vaccine developed by Moderna showed 94.1% efficacy at preventing COVID-19 after 2 doses.1
Common cutaneous adverse effects of the Moderna COVID-19 Vaccine include injection-site reactions, such as pain, induration, and erythema. Less frequently reported dermatologic adverse effects include diffuse bullous rash and hypersensitivity reactions.1 We report a case of reactivation of a BCG vaccination scar after the first dose of the Moderna COVID-19 Vaccine.
Case Report
A 48-year-old Asian man who was otherwise healthy presented with erythema, induration, and mild pruritus on the deltoid muscle of the left arm, near the scar from an earlier BCG vaccine, which he received at approximately 5 years of age when living in Taiwan. The patient received the first dose of the Moderna COVID-19 Vaccine approximately 5 to 7 cm distant from the BCG vaccination scar. One to 2 days after inoculation, the patient endorsed tenderness at the site of COVID-19 vaccination but denied systemic symptoms. He had never been given a diagnosis of COVID-19. His SARS-CoV-2 antibody status was unknown.
Eight days later, the patient noticed a well-defined, erythematous, indurated plaque with mild itchiness overlying and around the BCG vaccination scar that did not involve the COVID-19 vaccination site. The following day, the redness and induration became worse (Figure).
The patient was otherwise well. Vital signs were normal; there was no lymphadenopathy. The rash resolved without treatment over the next 4 days.
Comment
The BCG vaccine is an intradermal live attenuated virus vaccine used to prevent certain forms of tuberculosis and potentially other Mycobacterium infections. Although the vaccine is not routinely administered in the United States, it is part of the vaccination schedule in most countries, administered most often to newborns and infants. Administration of the BCG vaccine commonly results in mild localized erythema, swelling, and pain at the injection site. Most inoculated patients also develop an ulcer that heals with the characteristic BCG vaccination scar.2,3
There is evidence that the BCG vaccine can enhance the innate immune system response and might decrease the rate of infection by unrelated pathogens, including viruses.4 Several epidemiologic studies have suggested that the BCG vaccine might offer some protection against COVID-19, possibly due to a resemblance of the amino acid sequences of BCG and SARS-CoV-2, which might provoke cross-reactive T cells.5,6 Further studies are underway to determine whether the BCG vaccine is truly protective against COVID-19.
BCG vaccination scar reactivation presents as redness, swelling, or ulceration at the BCG injection site months to years after inoculation. Although erythema and induration of the BCG scar are not included in the diagnostic criteria of Kawasaki disease, likely due to variable vaccine requirements in different countries, these findings are largely recognized as specific for Kawasaki disease and present in approximately half of affected patients who received the BCG vaccine.2
Heat Shock Proteins—Heat shock proteins (HSPs) are produced by cells in response to stressors. The proposed mechanism of BCG vaccination scar reactivation is a cross-reaction between human homologue HSP 63 and Mycobacterium HSP 65, leading to hyperactivity of the immune system against BCG.7 There also are reports of reactivation of a BCG vaccination scar from measles infection and influenza vaccination.2,8,9 Most prior reports of BCG vaccination scar reactivation have been in pediatric patients; our patient is an adult who received the BCG vaccine more than 40 years ago.
Mechanism of Reactivation—The mechanism of BCG vaccination scar reactivation in our patient, who received the Moderna COVID-19 Vaccine, is unclear. Possible mechanisms include (1) release of HSP mediated by the COVID-19 vaccine, leading to an immune response at the BCG vaccine scar, or (2) another immune-mediated cross-reaction between BCG and the Moderna COVID-19 Vaccine mRNA nanoparticle or encoded spike protein antigen. It has been hypothesized that the BCG vaccine might offer some protection against COVID-19; this remains uncertain and is under further investigation.10 A recent retrospective cohort study showed that a BCG vaccination booster may decrease COVID-19 infection rates in higher-risk populations.11
Conclusion
We present a case of BCG vaccine scar reactivation occurring after a dose of the Moderna COVID-19 Vaccine, a likely underreported, self-limiting, cutaneous adverse effect of this mRNA vaccine.
- Baden LR, El Sahly HM, Essink B, et al; COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2020;384:403-416. doi:10.1056/NEJMoa2035389
- Muthuvelu S, Lim KS, Huang L-Y, et al. Measles infection causing bacillus Calmette-Guérin reactivation: a case report. BMC Pediatr. 2019;19:251. doi:10.1186/s12887-019-1635-z
- Fatima S, Kumari A, Das G, et al. Tuberculosis vaccine: a journey from BCG to present. Life Sci. 2020;252:117594. doi:10.1016/j.lfs.2020.117594
- O’Neill LAJ, Netea MG. BCG-induced trained immunity: can it offer protection against COVID-19? Nat Rev Immunol. 2020;20:335-337. doi:10.1038/s41577-020-0337-y
- Brooks NA, Puri A, Garg S, et al. The association of coronavirus disease-19 mortality and prior bacille Calmette-Guérin vaccination: a robust ecological analysis using unsupervised machine learning. Sci Rep. 2021;11:774. doi:10.1038/s41598-020-80787-z
- Tomita Y, Sato R, Ikeda T, et al. BCG vaccine may generate cross-reactive T-cells against SARS-CoV-2: in silico analyses and a hypothesis. Vaccine. 2020;38:6352-6356. doi:10.1016/j.vaccine.2020.08.045
- Lim KYY, Chua MC, Tan NWH, et al. Reactivation of BCG inoculation site in a child with febrile exanthema of 3 days duration: an early indicator of incomplete Kawasaki disease. BMJ Case Rep. 2020;13:E239648. doi:10.1136/bcr-2020-239648
- Kondo M, Goto H, Yamamoto S. First case of redness and erosion at bacillus Calmette-Guérin inoculation site after vaccination against influenza. J Dermatol. 2016;43:1229-1231. doi:10.1111/1346-8138.13365
- Chavarri-Guerra Y, Soto-Pérez-de-Celis E. Erythema at the bacillus Calmette-Guerin scar after influenza vaccination. Rev Soc Bras Med Trop. 2019;53:E20190390. doi:10.1590/0037-8682-0390-2019
- Fu W, Ho P-C, Liu C-L, et al. Reconcile the debate over protective effects of BCG vaccine against COVID-19. Sci Rep. 2021;11:8356. doi:10.1038/s41598-021-87731-9
- Amirlak L, Haddad R, Hardy JD, et al. Effectiveness of booster BCG vaccination in preventing COVID-19 infection. Hum Vaccin Immunother. 2021;17:3913-3915. doi:10.1080/21645515.2021.1956228
- Baden LR, El Sahly HM, Essink B, et al; COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2020;384:403-416. doi:10.1056/NEJMoa2035389
- Muthuvelu S, Lim KS, Huang L-Y, et al. Measles infection causing bacillus Calmette-Guérin reactivation: a case report. BMC Pediatr. 2019;19:251. doi:10.1186/s12887-019-1635-z
- Fatima S, Kumari A, Das G, et al. Tuberculosis vaccine: a journey from BCG to present. Life Sci. 2020;252:117594. doi:10.1016/j.lfs.2020.117594
- O’Neill LAJ, Netea MG. BCG-induced trained immunity: can it offer protection against COVID-19? Nat Rev Immunol. 2020;20:335-337. doi:10.1038/s41577-020-0337-y
- Brooks NA, Puri A, Garg S, et al. The association of coronavirus disease-19 mortality and prior bacille Calmette-Guérin vaccination: a robust ecological analysis using unsupervised machine learning. Sci Rep. 2021;11:774. doi:10.1038/s41598-020-80787-z
- Tomita Y, Sato R, Ikeda T, et al. BCG vaccine may generate cross-reactive T-cells against SARS-CoV-2: in silico analyses and a hypothesis. Vaccine. 2020;38:6352-6356. doi:10.1016/j.vaccine.2020.08.045
- Lim KYY, Chua MC, Tan NWH, et al. Reactivation of BCG inoculation site in a child with febrile exanthema of 3 days duration: an early indicator of incomplete Kawasaki disease. BMJ Case Rep. 2020;13:E239648. doi:10.1136/bcr-2020-239648
- Kondo M, Goto H, Yamamoto S. First case of redness and erosion at bacillus Calmette-Guérin inoculation site after vaccination against influenza. J Dermatol. 2016;43:1229-1231. doi:10.1111/1346-8138.13365
- Chavarri-Guerra Y, Soto-Pérez-de-Celis E. Erythema at the bacillus Calmette-Guerin scar after influenza vaccination. Rev Soc Bras Med Trop. 2019;53:E20190390. doi:10.1590/0037-8682-0390-2019
- Fu W, Ho P-C, Liu C-L, et al. Reconcile the debate over protective effects of BCG vaccine against COVID-19. Sci Rep. 2021;11:8356. doi:10.1038/s41598-021-87731-9
- Amirlak L, Haddad R, Hardy JD, et al. Effectiveness of booster BCG vaccination in preventing COVID-19 infection. Hum Vaccin Immunother. 2021;17:3913-3915. doi:10.1080/21645515.2021.1956228
Practice Points
- BCG vaccination scar reactivation is a potential benign, self-limited reaction in patients who receive the Moderna COVID-19 Vaccine.
- Symptoms of BCG vaccination scar reactivation, which is seen more commonly in children with Kawasaki disease, include redness, swelling, and ulceration.
