Mycoplasma-Induced Rash and Mucositis: 2 Cases in Adults

AUTHORS:
Heena S. Sheth, MD, MPH • David J. McAdams, MD • Maria Petroulakis, MD

AFFILIATIONS:
Department of Medicine, Division of General Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

CITATION:
Sheth HS, McAdams DJ, Petroulakis M. Mycoplasma-induced rash and mucositis: 2 cases in adults. Consultant. 2021;61(4):e32-e35. doi:10.25270/con.2020.08.00008

Received March 9, 2020. Accepted July 6, 2020. Published online August 15, 2020. 

DISCLOSURES:
The authors report no relevant financial relationships.

CORRESPONDENCE:
Heena S. Sheth, MD, MPH, Research Assistant Professor, Department of Medicine, University of Pittsburgh, 200 Lothrop St, Ste G100, Pittsburgh, PA 15213 (shethhs@upmc.edu)

Mycoplasma pneumoniae-induced rash and mucositis (MIRM) is distinct from Mycoplasma-associated Steven-Johnson syndrome (SJS) and erythema multiforme (EM).^1,2 MIRM features sparse cutaneous manifestations and has an excellent prognosis with supportive care. MIRM occurs most commonly in school-aged children and teenagers (mean age, 12 years), noticeably in boys.^3,4 Only in recent years have a few case reports of MIRM in adults been reported, describing presentations that vary in severity, involved sites, and prognosis.^5,6

We present 2 adult cases of MIRM following pneumonia with mucositis with oral, ocular, and genital involvement and with sparse cutaneous lesions. We review the literature and discuss the knowledge gap regarding MIRM that warrants further studies with the aim of preventing MIRM, reducing its complications, and guiding its management.

CASE 1

A 22-year-old man presented to our emergency department (ED) for evaluation of increasing fatigue, fever, chills, conjunctival erythema, sore throat, nonproductive cough and mouth lesions.

Four days prior, he had visited his university’s student health center for evaluation of a gradual onset of fatigue, purulent rhinorrhea, and headache. Physical examination findings at that time were significant for fever and left lower-lobe crackles. A radiograph showed left lower-lobe pneumonia (Figure 1).

Figure 1. Lateral view (top) and anteroposterior view (bottom) chest radiographs of a 22-year-old man showing left lower-lobe pneumonia.

He was prescribed azithromycin, 500 mg, for 5 days and discharged to home. Over the next 3 to 4 days, he developed increasing fatigue, mouth pain and ulcers, an inability to eat or drink, conjunctival erythema, and a penile rash. On ninth day after the onset of symptoms, he presented to our ED. He had taken the antibiotics as prescribed.

His medical history, specifically for HIV infection and autoimmune diseases such as systemic lupus erythematosus, was negative. His vaccinations were up to date, and he was not on any medication. He had no known allergies. His family medical history was positive for malignancies in several family members. He was a nonsmoker and denied the use of alcohol or recreational drugs. He was in a monogamous relationship with his girlfriend.

Physical examination findings were significant for a temperature of 38.0 °C and mild tachycardia of 100 beats/min. He was alert and oriented. His lungs were clear, with no wheezing or crackles and with normal air entry bilaterally. He had bilateral conjunctivitis (Figure 2) with photophobia. The rest of the ophthalmoscopic examination findings were normal, with visual acuity of 20/20 without correction and full range of motion bilaterally. Oral lesions were present over the soft palate, with hemorrhagic crusts over both lips (Figure 3). Neck examination findings were positive for bilateral, tender, soft postauricular and cervical adenopathy. He had cutaneous ulcers with hemorrhagic cysts over the penis (Figure 4). The rest of the physical examination findings were normal, except for a single small vesicular lesion over the third left toe.

Figure 2. Bilateral conjunctivitis in a 22-year-old man.

Figure 3. Oral lesions were present over the soft palate, with hemorrhagic crusts over both lips of a 22-year-old man.

Figure 4. Cutaneous ulcers with hemorrhagic cysts over the penis of a 22-year-old man.

Laboratory confirmation for Mycoplasma infection was obtained from positive immunoglobulin M (IgM) antibodies. The patient was HIV-negative, and blood cell counts were within the normal range with no eosinophilia.

The patient completed a course of oral azithromycin, 250 mg/d, for 7 days, which had been started in the student health clinic; prednisone, 1 mg/kg, for 5 days; nystatin/hydrocortisone/diphenhydramine mouthwash 4 times a day; topical benzocaine anesthetic lozenges as needed; intravenous fluids (0.9% sodium chloride solution, 1000 mL at 100 mL/h); and erythromycin ophthalmic ointment, 0.5%, in both eyes at night. The patient improved and was discharged to home 2 days after admission. At 2 weeks’ follow-up, he had returned to baseline, with very minimal evidence of mucosal erythema.

CASE 2

A 23-year-old man presented to an urgent care clinic with a 7-day history of rhinorrhea, cough, sore throat, and chest and sinus congestion. He was treated for presumed bronchitis with amoxicillin-clavulanate, 500 mg twice daily for 7 days, and an ipratropium/albuterol inhaler as needed, and was discharged home.

He presented to the ED 2 days later after experiencing no improvement of symptoms and reporting mild chest pain, coughing, and minimal throat discomfort. At this visit, he was afebrile. However, chest radiographs showed perihilar opacities. The amoxicillin-clavulanate was discontinued, and doxycycline (100 mg twice daily for 7 days), methylprednisolone (4 mg once daily, which the patient took for 3 days and had stopped taking), and ibuprofen (600 mg a maximum of 4 times a day as needed) were started. He was instructed to continue his ipratropium/albuterol inhaler for symptomatic relief and was instructed to return to the ED if he developed shortness of breath or any other concerning symptoms.

On day 11 after his initial presentation to the urgent care clinic, he presented again to the ED with red eyes and painful swallowing. At this time, he was admitted to the hospital. On physical examination, he was afebrile with stable vital signs, bilateral conjunctivitis (Figure 5), and oral mucosal lesions (Figure 6). He did not have any skin lesions and denied urogenital lesions; however, he refused a genital examination.

Figure 5. Bilateral conjunctivitis in a 23-year-old man.

Figure 6. Oral mucosal lesions in a 23-year-old man.

A consultant dermatologist confirmed the findings of mucositis, presumably associated with Mycoplasma pneumoniae infection, and recommended a Mycoplasma serology test, a macrolide antibiotic, and supportive care with a steroid and analgesic mouthwash. A consultant ophthalmologist noted bilateral conjunctivitis and some synechiae. The patient had had childhood asthma and no relevant family history. He was sexually active with one partner and reported no recreational drug use, smoking history, or HIV.

Laboratory test results at admission were significant for an elevated white blood cell count of 13,700/µL and positive Mycoplasma IgM antibodies. Admission chest radiographs showed left perihilar opacities, confirming atypical pneumonia (Figure 7).

Figure 7. Chest radiographs showed left perihilar opacities, confirming atypical pneumonia in a 23-year-old man.

His antibiotic was changed from doxycycline to intravenous ceftriaxone, 1 mg once daily, and intravenous azithromycin, 500 mg once daily. Supportive treatment with analgesic mouthwash (5 mL lidocaine topical, 2%), ophthalmic moxifloxacin, and prednisone drops 4 times daily were continued during the hospital stay as per the recommendations of the ophthalmologist. Continuous hydration with lactated Ringer solution, 70 mL/h, was continued after an initial 1000-mL bolus.

His symptoms improved over the course of 3 days, and he was discharged to home with instructions to complete the antibiotic course. He was discharged on doxycycline, 100 mg twice daily for 10 days, as well as supportive oral care and ophthalmic care as was administered in the hospital. At the time of discharge, he was able to eat and drink with no discomfort and had very minimal redness of the eyes.

DISCUSSION

Both of these young men presented initially as a mild upper respiratory infection managed at home with hydration, cough suppressant, and antibiotics. Both patients continued to be symptomatic for more than 5 days and were diagnosed as having community-acquired pneumonia and later, after confirmatory serology test results, as having MIRM. The patient in the first case presented during the spring and the second presented in the fall, when Mycoplasma infections are most common.³ Both patients had prominent oral mucositis, and the first patient also had genital lesions and a very few skin lesions; both patients tested positive for Mycoplasma antibodies, confirming the diagnosis of MIRM.

Both cases followed the epidemiologic characteristics of M pneumoniae and MIRM. Mycoplasma infections are common in crowded residential environments such as boarding schools, college dormitories, and prisons and occur more frequently in the male population. MIRM cases present with 3 characteristic features: atypical pneumonia; laboratory confirmation of M pneumoniae by IgM antibodies, by positive cultures of organism from an oropharyngeal swab or skin lesion, and/or by serial cold agglutinin titers; and a rash on 2 or more mucosal sites with or without a mild, scattered, cutaneous target rash.¹ Both of our patients shared these features, with a very scattered rash in one and no skin involvement in the other. MIRM cases can be further classified into 3 types based on cutaneous involvement: classic MIRM, which presents with cutaneous involvement; MIRM sine rash, which presents with few fleeting lesions or no skin rash at all; and severe MIRM, which presents with an extensive cutaneous rash. Our cases would be classified as MIRM sine rash, given the very mild cutaneous involvement.

Most published MIRM case reports did not report patients’ history of allergies or immune disorders. Mycoplasma’s unique characteristic of a lack of a cell wall has been implicated in antibiotic resistance and immune response.⁷ Mucocutaneous involvement with M pneumoniae has been attributed to multiple etiologies.⁸ The mechanism of MIRM is thought to occur as a result of the formation of cross-reacting autoantibodies, which originally target glycolipid antigens of M pneumoniae, but later these antibodies attack the mucosal cells with a similar epitope as M pneumoniae, causing cytotoxic damage that results in mucositis.⁹ Recurrence of M pneumoniae infection has been reported in the same individual as well as in the same family, the latter of which suggests a possible genetic association,^10-12 which requires further studies.

The presentation of atypical pneumonia with minimal cough and at times a lack of fever tends to delay the diagnosis of pneumonia and serology testing for Mycoplasma, as happened in both of our reported cases. The prognosis of MIRM is very favorable with supportive treatment. In cases of severe mucosal involvement, treatment with corticosteroids and rarely immunoglobulins may be required. Antibiotics are routinely prescribed to cover the infection, in addition to oral hygiene and hydration, proper eye care to prevent long-term complications of synechiae and vision problems, and a urology consult for urogenital lesions to prevent strictures, although complications are rare.

A vaccine is not available for M pneumoniae infection, and there have been some reports of the bacteria developing resistance to macrolide antibiotics.¹³ This makes it imperative to have guidelines for appropriate management of infections and to use antibiotics judiciously. Health care providers, including emergency medicine clinicians, should be educated to recognize MIRM. Careful inquiry about previous infections in the patient and his or her family, exposure to infected individuals, and environmental factors such as crowded dormitories are a must to establish the diagnosis. A well-designed study of effective management and development of guidelines is warranted, incorporating genetic predisposition, diagnostic criteria, severity, and prognostic criteria, as well as guidelines for treatment.

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