Oral and Penile Lesions in a Young Man
Gordon T. Moffat, MD1; Franco Falcone, MD1
Author Affiliations Article Information
1Department of Internal Medicine, State University of New York, Downstate Medical Center, Brooklyn
JAMA. Published online June 24, 2019. doi:10.1001/jama.2019.7804
Case
A 28-year-old man presented to the emergency department with diffuse oral lesions, fever, and nonproductive cough for 1 week. He was diagnosed with herpes simplex virus (HSV) and discharged home with acyclovir. Two days later, he returned with worsening oral lesions, painful phonation, poor oral intake, odynophagia, and new painful penile lesions. He denied any abdominal pain, diarrhea, rectal bleeding, weight loss, arthralgia, fatigue, vision changes, or skin rashes. He reported a similar episode of widespread oral lesions 18 months earlier that was less severe and self-resolving. He had no other medical conditions, took no medications, and was sexually monogamous with his wife, who was asymptomatic.
The patient was hemodynamically stable and had a normal respiratory examination. He had a fever (39.4°C) on presentation, but his temperature abated overnight and he remained afebrile for the rest of the admission. His superior and inferior lips had extensive well-circumscribed erosions and ulcerations with erythematous edges, crusting, and a gray-white base (Figure, left). Lesions extended into the buccal mucosa and soft palate. His tongue was enlarged with fissures. A genital examination showed similar lesions on the penis, with scalloped borders (Figure, right). There were no skin lesions, lymphadenopathy, or hepatosplenomegaly.
Left, Extensive well-circumscribed oral lesions limited to the mucosa in a 28-year-old man. Right, Similar lesions with scalloped borders on the distal shaft and glans of the penis in the same patient.
Left, Extensive well-circumscribed oral lesions limited to the mucosa in a 28-year-old man. Right, Similar lesions with scalloped borders on the distal shaft and glans of the penis in the same patient.
Results of laboratory tests from the emergency department were normal, and a chest radiograph showed no evidence of pneumonia. Results of further testing for antinuclear antibodies, erythrocyte sedimentation rate, C-reactive protein level, HIV, HSV serology, syphilis, chlamydia, and gonorrhea were negative. Bacterial and viral cultures of the oral and penile lesions were also negative. Serum enzyme immunoassay for Mycoplasma pneumoniae IgM was positive at 1280 U/mL. The patient did not consent to a punch biopsy of the oral lesions.
What Would You Do Next?
Perform upper endoscopy and colonoscopy
Test for anti–double-stranded DNA antibodies
Prescribe oral azithromycin
Prescribe oral suspension nystatin
Discussion
Diagnosis
M pneumoniae–induced rash and mucositis (MIRM)
What to Do Next
C. Prescribe oral azithromycin
The key to the correct diagnosis is the elevated M pneumoniae IgM titers in a patient with a nonproductive cough and 2 sites of mucosal lesions. Although Crohn disease and systemic lupus erythematosus can present with oral lesions, the patient’s lack of associated gastrointestinal or musculoskeletal symptoms make these diagnoses unlikely. Since the patient is HIV-negative and immunocompetent, oral candidiasis is unlikely.
Discussion:
M pneumoniae infections are often asymptomatic but can also present as upper respiratory tract infections, bronchitis, or pneumonia. Less commonly, patients with M pneumoniae infection can have mucocutaneous manifestations. MIRM is an extremely rare complication of M pneumoniae infection (exact incidence unknown) and often is mistaken for Stevens-Johnson syndrome or HSV-associated erythema multiforme. Typically, MIRM occurs in older children or adolescents and involves the oral, ocular, and genitourinary mucosal surfaces in 94%, 82%, and 63% of cases, respectively. Skin involvement is typically sparse and occurs in an acral distribution.1
In 2015, Caravan et al proposed a diagnostic criterion for MIRM that included 10% or less body surface area detachment, 2 or more mucosal sites involved, few vesiculobullous skin lesions or atypical targets, and clinical or laboratory evidence of atypical pneumonia.1 The gold standard for diagnosis is M pneumoniae nucleic acid amplification testing (NAAT) because of its superior sensitivity and specificity in an acute infection.2 However, NAAT is costly and often time-inefficient to run (eg, if it needs to be sent to an outside laboratory).3 Serum enzyme immunoassay IgM testing is an alternative that is more widely available, faster, and less costly2,3; however, recent studies have demonstrated both significant heterogeneity in sensitivity and specificity and inconsistent diagnostic accuracy.3 This is in part because IgM antibodies begin to appear 7 to 9 days after initial infection, with a peak at 3 to 6 weeks, and therefore may be missed when testing during acute infection or reinfection in adults.3-6 A systematic review concluded that during the acute phase of infection, the use of IgM in combination with polymerase chain reaction allows for a more precise and reliable M pneumoniae diagnosis.3
There are no evidence-based guidelines for the treatment of MIRM. In a systematic review of 202 cases of MIRM, 80% of patients received antibiotics, 35% received systemic corticosteroids, and 8% received intravenous immunoglobulin.1M pneumoniae is very susceptible to antibiotics that interfere with protein and DNA synthesis, which includes macrolides, tetracyclines, and quinolones.7,8 Nevertheless, the full clinical benefits of antimicrobial therapy are unclear, and further studies are required. The efficacy and clinical benefit of systemic corticosteroid and intravenous immunoglobulin therapy in the treatment of MIRM are not definitive.1
Based on the same systematic review, MIRM had a good prognosis in 81% of patients; however, 4% required admission to a medical intensive care unit.1 Mortality was 3%; however, these instances were all from the 1940s (preantibiotic era). Pulmonary complications and lack of treatment with antibiotics were associated with poorer outcomes.1 Other complications included permanent ocular, oral, genital, or cutaneous lesions or B-cell lymphopenia.1,9
Patient Outcome
NAAT was not performed in this instance because it was unavailable in-house; the diagnosis of MIRM was based on physical examination and positive IgM titers. The patient was treated with 5 days of oral azithromycin and had full resolution of cough and mucosal symptoms 1 week later, which supported the diagnosis. Follow-up IgM convalescent titers completed 7 months after treatment had a more than 4-fold decrease from the acute titers, further supporting the diagnosis.4
Back to top Article Information
Corresponding Author: Franco Falcone, MD, Department of Medicine, State University of New York Downstate Medical Center, 450 Clarkson Ave, MSC-50, Brooklyn, NY 11203 (franco.falcone@nychhc.org).
Published Online: June 24, 2019. doi:10.1001/jama.2019.7804
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank Christopher Torsitano, BS, and Barrett Torre, BA (College of Medicine, State University of New York, Downstate Medical Center), for help with the literature review; Silvia Mancebo, MD, and Miriam Lieberman, MD (Department of Dermatology, State University of New York, Downstate Medical Center), for help with photograph acquisition; and Samy McFarlane, MD, MPH, MBA (Department of Internal Medicine, State University of New York, Downstate Medical Center), for help with the overall content and editorial review. None of these individuals received compensation for their contributions. We also thank the patient for providing permission to share his information.
Section Editor: Mary McGrae McDermott, MD, Senior Editor.
Submissions: We encourage authors to submit papers for consideration as a JAMA Clinical Challenge. Please contact Dr McDermott at mdm608@northwestern.edu.
References
1.
Canavan TN, Mathes EF, Frieden I, Shinkai K. Mycoplasma pneumoniae-induced rash and mucositis as a syndrome distinct from Stevens-Johnson syndrome and erythema multiforme: a systematic review. J Am Acad Dermatol. 2015;72(2):239-245. doi:10.1016/j.jaad.2014.06.026PubMedGoogle ScholarCrossref
2.
Loens K, Ieven M. Mycoplasma pneumoniae: current knowledge on nucleic acid amplification techniques and serological diagnostics. Front Microbiol. 2016;7:448. doi:10.3389/fmicb.2016.00448PubMedGoogle ScholarCrossref
3.
Canadian Agency for Drugs and Technologies in Health. Serum IgM and Molecular Tests for Mycoplasma pneumoniae Detection: A Review of Diagnostic Test Accuracy, Clinical Effectiveness, Cost-Effectiveness, and Guidelines. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health; 2015.
4.
Lee SC, Youn YS, Rhim JW, Kang JH, Lee KY. Early serologic diagnosis of Mycoplasma pneumoniae pneumonia: an observational study on changes in titers of specific IgM antibodies and cold agglutinins. Medicine (Baltimore). 2016;95(19):e3605. doi:10.1097/MD.0000000000003605PubMedGoogle ScholarCrossref
5.
Lee WJ, Huang EY, Tsai CM, et al. Role of serum Mycoplasma pneumoniae IgA, IgM, and IgG in the diagnosis of Mycoplasma pneumoniae–related pneumonia in school-age children and adolescents. Clin Vaccine Immunol. 2017;24(1):e00471-e16. doi:10.1128/CVI.00471-16PubMedGoogle ScholarCrossref
6.
Sillis M. The limitations of IgM assays in the serological diagnosis of Mycoplasma pneumoniae infections. J Med Microbiol. 1990;33(4):253-258. doi:10.1099/00222615-33-4-253PubMedGoogle ScholarCrossref
7.
Pereyre S, Goret J, Bébéar C. Mycoplasma pneumoniae: current knowledge on macrolide resistance and treatment. Front Microbiol. 2016;7:974. doi:10.3389/fmicb.2016.00974PubMedGoogle ScholarCrossref
8.
Taylor-Robinson D, Bébéar C. Antibiotic susceptibilities of mycoplasmas and treatment of mycoplasmal infections. J Antimicrob Chemother. 1997;40(5):622-630. doi:10.1093/jac/40.5.622PubMedGoogle ScholarCrossref
9.
Martire B, Foti C, Cassano N, Buquicchio R, Del Vecchio GC, De Mattia D. Persistent B-cell lymphopenia, multiorgan disease, and erythema multiforme caused by Mycoplasma pneumoniae infection. Pediatr Dermatol. 2005;22(6):558-560. doi:10.1111/j.1525-1470.2005.00140.xPubMedGoogle ScholarCrossref
Gordon T. Moffat, MD1; Franco Falcone, MD1
Author Affiliations Article Information
1Department of Internal Medicine, State University of New York, Downstate Medical Center, Brooklyn
JAMA. Published online June 24, 2019. doi:10.1001/jama.2019.7804
Case
A 28-year-old man presented to the emergency department with diffuse oral lesions, fever, and nonproductive cough for 1 week. He was diagnosed with herpes simplex virus (HSV) and discharged home with acyclovir. Two days later, he returned with worsening oral lesions, painful phonation, poor oral intake, odynophagia, and new painful penile lesions. He denied any abdominal pain, diarrhea, rectal bleeding, weight loss, arthralgia, fatigue, vision changes, or skin rashes. He reported a similar episode of widespread oral lesions 18 months earlier that was less severe and self-resolving. He had no other medical conditions, took no medications, and was sexually monogamous with his wife, who was asymptomatic.
The patient was hemodynamically stable and had a normal respiratory examination. He had a fever (39.4°C) on presentation, but his temperature abated overnight and he remained afebrile for the rest of the admission. His superior and inferior lips had extensive well-circumscribed erosions and ulcerations with erythematous edges, crusting, and a gray-white base (Figure, left). Lesions extended into the buccal mucosa and soft palate. His tongue was enlarged with fissures. A genital examination showed similar lesions on the penis, with scalloped borders (Figure, right). There were no skin lesions, lymphadenopathy, or hepatosplenomegaly.
Left, Extensive well-circumscribed oral lesions limited to the mucosa in a 28-year-old man. Right, Similar lesions with scalloped borders on the distal shaft and glans of the penis in the same patient.
Left, Extensive well-circumscribed oral lesions limited to the mucosa in a 28-year-old man. Right, Similar lesions with scalloped borders on the distal shaft and glans of the penis in the same patient.
Results of laboratory tests from the emergency department were normal, and a chest radiograph showed no evidence of pneumonia. Results of further testing for antinuclear antibodies, erythrocyte sedimentation rate, C-reactive protein level, HIV, HSV serology, syphilis, chlamydia, and gonorrhea were negative. Bacterial and viral cultures of the oral and penile lesions were also negative. Serum enzyme immunoassay for Mycoplasma pneumoniae IgM was positive at 1280 U/mL. The patient did not consent to a punch biopsy of the oral lesions.
What Would You Do Next?
Perform upper endoscopy and colonoscopy
Test for anti–double-stranded DNA antibodies
Prescribe oral azithromycin
Prescribe oral suspension nystatin
Discussion
Diagnosis
M pneumoniae–induced rash and mucositis (MIRM)
What to Do Next
C. Prescribe oral azithromycin
The key to the correct diagnosis is the elevated M pneumoniae IgM titers in a patient with a nonproductive cough and 2 sites of mucosal lesions. Although Crohn disease and systemic lupus erythematosus can present with oral lesions, the patient’s lack of associated gastrointestinal or musculoskeletal symptoms make these diagnoses unlikely. Since the patient is HIV-negative and immunocompetent, oral candidiasis is unlikely.
Discussion:
M pneumoniae infections are often asymptomatic but can also present as upper respiratory tract infections, bronchitis, or pneumonia. Less commonly, patients with M pneumoniae infection can have mucocutaneous manifestations. MIRM is an extremely rare complication of M pneumoniae infection (exact incidence unknown) and often is mistaken for Stevens-Johnson syndrome or HSV-associated erythema multiforme. Typically, MIRM occurs in older children or adolescents and involves the oral, ocular, and genitourinary mucosal surfaces in 94%, 82%, and 63% of cases, respectively. Skin involvement is typically sparse and occurs in an acral distribution.1
In 2015, Caravan et al proposed a diagnostic criterion for MIRM that included 10% or less body surface area detachment, 2 or more mucosal sites involved, few vesiculobullous skin lesions or atypical targets, and clinical or laboratory evidence of atypical pneumonia.1 The gold standard for diagnosis is M pneumoniae nucleic acid amplification testing (NAAT) because of its superior sensitivity and specificity in an acute infection.2 However, NAAT is costly and often time-inefficient to run (eg, if it needs to be sent to an outside laboratory).3 Serum enzyme immunoassay IgM testing is an alternative that is more widely available, faster, and less costly2,3; however, recent studies have demonstrated both significant heterogeneity in sensitivity and specificity and inconsistent diagnostic accuracy.3 This is in part because IgM antibodies begin to appear 7 to 9 days after initial infection, with a peak at 3 to 6 weeks, and therefore may be missed when testing during acute infection or reinfection in adults.3-6 A systematic review concluded that during the acute phase of infection, the use of IgM in combination with polymerase chain reaction allows for a more precise and reliable M pneumoniae diagnosis.3
There are no evidence-based guidelines for the treatment of MIRM. In a systematic review of 202 cases of MIRM, 80% of patients received antibiotics, 35% received systemic corticosteroids, and 8% received intravenous immunoglobulin.1M pneumoniae is very susceptible to antibiotics that interfere with protein and DNA synthesis, which includes macrolides, tetracyclines, and quinolones.7,8 Nevertheless, the full clinical benefits of antimicrobial therapy are unclear, and further studies are required. The efficacy and clinical benefit of systemic corticosteroid and intravenous immunoglobulin therapy in the treatment of MIRM are not definitive.1
Based on the same systematic review, MIRM had a good prognosis in 81% of patients; however, 4% required admission to a medical intensive care unit.1 Mortality was 3%; however, these instances were all from the 1940s (preantibiotic era). Pulmonary complications and lack of treatment with antibiotics were associated with poorer outcomes.1 Other complications included permanent ocular, oral, genital, or cutaneous lesions or B-cell lymphopenia.1,9
Patient Outcome
NAAT was not performed in this instance because it was unavailable in-house; the diagnosis of MIRM was based on physical examination and positive IgM titers. The patient was treated with 5 days of oral azithromycin and had full resolution of cough and mucosal symptoms 1 week later, which supported the diagnosis. Follow-up IgM convalescent titers completed 7 months after treatment had a more than 4-fold decrease from the acute titers, further supporting the diagnosis.4
Back to top Article Information
Corresponding Author: Franco Falcone, MD, Department of Medicine, State University of New York Downstate Medical Center, 450 Clarkson Ave, MSC-50, Brooklyn, NY 11203 (franco.falcone@nychhc.org).
Published Online: June 24, 2019. doi:10.1001/jama.2019.7804
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank Christopher Torsitano, BS, and Barrett Torre, BA (College of Medicine, State University of New York, Downstate Medical Center), for help with the literature review; Silvia Mancebo, MD, and Miriam Lieberman, MD (Department of Dermatology, State University of New York, Downstate Medical Center), for help with photograph acquisition; and Samy McFarlane, MD, MPH, MBA (Department of Internal Medicine, State University of New York, Downstate Medical Center), for help with the overall content and editorial review. None of these individuals received compensation for their contributions. We also thank the patient for providing permission to share his information.
Section Editor: Mary McGrae McDermott, MD, Senior Editor.
Submissions: We encourage authors to submit papers for consideration as a JAMA Clinical Challenge. Please contact Dr McDermott at mdm608@northwestern.edu.
References
1.
Canavan TN, Mathes EF, Frieden I, Shinkai K. Mycoplasma pneumoniae-induced rash and mucositis as a syndrome distinct from Stevens-Johnson syndrome and erythema multiforme: a systematic review. J Am Acad Dermatol. 2015;72(2):239-245. doi:10.1016/j.jaad.2014.06.026PubMedGoogle ScholarCrossref
2.
Loens K, Ieven M. Mycoplasma pneumoniae: current knowledge on nucleic acid amplification techniques and serological diagnostics. Front Microbiol. 2016;7:448. doi:10.3389/fmicb.2016.00448PubMedGoogle ScholarCrossref
3.
Canadian Agency for Drugs and Technologies in Health. Serum IgM and Molecular Tests for Mycoplasma pneumoniae Detection: A Review of Diagnostic Test Accuracy, Clinical Effectiveness, Cost-Effectiveness, and Guidelines. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health; 2015.
4.
Lee SC, Youn YS, Rhim JW, Kang JH, Lee KY. Early serologic diagnosis of Mycoplasma pneumoniae pneumonia: an observational study on changes in titers of specific IgM antibodies and cold agglutinins. Medicine (Baltimore). 2016;95(19):e3605. doi:10.1097/MD.0000000000003605PubMedGoogle ScholarCrossref
5.
Lee WJ, Huang EY, Tsai CM, et al. Role of serum Mycoplasma pneumoniae IgA, IgM, and IgG in the diagnosis of Mycoplasma pneumoniae–related pneumonia in school-age children and adolescents. Clin Vaccine Immunol. 2017;24(1):e00471-e16. doi:10.1128/CVI.00471-16PubMedGoogle ScholarCrossref
6.
Sillis M. The limitations of IgM assays in the serological diagnosis of Mycoplasma pneumoniae infections. J Med Microbiol. 1990;33(4):253-258. doi:10.1099/00222615-33-4-253PubMedGoogle ScholarCrossref
7.
Pereyre S, Goret J, Bébéar C. Mycoplasma pneumoniae: current knowledge on macrolide resistance and treatment. Front Microbiol. 2016;7:974. doi:10.3389/fmicb.2016.00974PubMedGoogle ScholarCrossref
8.
Taylor-Robinson D, Bébéar C. Antibiotic susceptibilities of mycoplasmas and treatment of mycoplasmal infections. J Antimicrob Chemother. 1997;40(5):622-630. doi:10.1093/jac/40.5.622PubMedGoogle ScholarCrossref
9.
Martire B, Foti C, Cassano N, Buquicchio R, Del Vecchio GC, De Mattia D. Persistent B-cell lymphopenia, multiorgan disease, and erythema multiforme caused by Mycoplasma pneumoniae infection. Pediatr Dermatol. 2005;22(6):558-560. doi:10.1111/j.1525-1470.2005.00140.xPubMedGoogle ScholarCrossref
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