American Journal of Transplantation Images in Transplantation – Continuing Medical Education (CME)

Each month, the American Journal of Transplantation will feature Images in Transplantation, a journal-based CME activity, chosen to educate participants on current developments in the science and imaging of transplantation. Participants can earn 1 AMA PRA Category 1 Credit™ per article at their own pace.

This month's feature article is titled: “Fever, Maculopapular Rash and Severe Aphthous Stomatitis in a Renal Transplant Patient.”

Accreditation and Designation Statement

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Blackwell Futura Media Services, the American Society of Transplant Surgeons and the American Society of Transplantation. Blackwell Futura Media Services is accredited by the ACCME to provide continuing medical education for physicians.

Blackwell Futura Media Services designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Statement of Need

Transplant recipients may develop oral lesions ranging from simple ulcerations to precancerous and frankly malignant neoplasms. This learning activity will address the knowledge gap and issues important in determining the etiology of fever, aphthous stomatitis and maculopapular rash in immunosuppressed patients.

Purpose of Activity

This activity is designed to improve the practitioner's competence in the recognition, diagnosis and treatment of viral infections and their potential complications in solid organ transplant recipients.

Identification of Practice Gap

Transplant recipients frequently suffer from viral infections. However, not all clinicians are familiar with the presentation, diagnosis and management of viral infections in patients receiving immunosuppressive treatment. Maintaining a heightened index of suspicion can prevent unnecessary investigations and antibiotic treatment, and may lead to early diagnosis of the disease.

Learning Objectives

Upon completion of this educational activity, participants will be able to:

  • Recognize characteristic features of a distinct viral infection, leading to earlier identification and commencement of a suitable treatment in patients receiving immunosuppressive treatment.
  • Define potential complications of this unusual infection in adults.
  • Determine available treatment options for this disease.
  • Restate pathophysiologic aspects of aphthous stomatitis.

Target Audience

This activity has been designed to meet the educational needs of physicians and surgeons in the field of transplantation.


No commercial support has been accepted related to the development or publication of this activity. Blackwell Futura Media Services has reviewed all disclosures and resolved or managed all identified conflicts of interest, as applicable.


Allan D. Kirk, MD, PhD, FACS, has no relevant financial relationships to disclose.


Sandy Feng, MD, PhD, discloses stock and/or equity interest in Abbott, Amgen, Charles River Labs, Eli Lily, Glaxo–Smith–Klein, Hospira, Johnson & Johnson, Express Scripts, Medco, Merck, Pfizer, and Stryker; research support from Cumberland and Quark; and research support and consulting work for Novartis.

Douglas W. Hanto, MD, PhD, has no relevant financial relationships to disclose.


Stefan Reuter, MD, Marc A. Schläter, MD, Hermann Pavenstädt, MD, and Barbara Suwelack, MD, have no relevant financial relationships to disclose.

ASTS Staff

Mina Behari, Director of Education, has no relevant financial relationships to disclose.

This manuscript underwent peer review in line with the standards of editorial integrity and publication ethics maintained by the American Journal of Transplantation. The peer reviewers have no relevant financial relationships to disclose. The peer review process for the American Journal of Transplantation is blinded. As such, the identities of the reviewers are not disclosed in line with the standard accepted practices of medical journal peer review.

Instructions on Receiving CME Credit

This activity is designed to be completed within an hour. Physicians should claim only those credits that refl ect the time actually spent in the activity. This activity will be available for CME credit for twelve months following its publication date. At that time, it will be reviewed and potentially updated and extended for an additional twelve months.

Follow these steps to participate, answer the questions and claim your CME credit:

  • Log on to
  • Read the learning objectives, target audience, and activity disclosures.
  • Read the article in print or online format.
  • Reflect on the article.
  • Access the CME Exam, and choose the best answer to each question.
  • Complete the required evaluation and print your CME certificate.

A 27-year-old Caucasian man with end stage renal failure secondary to IgA nephropathy presented six years after renal transplantation with new onset of fever (39.5°C) and a sore throat to his family physician. Immunosuppressive regime consisted of tacrolimus (11.5 ng/mL), mycophenolate mofetil (250 mg bid) and prednisolone 5 mg. Graft function remained stable with a serum creatinine of 1 mg/dL. Physical examination showed pharyngitis and tender cervical lymph nodes. Therapy with amoxicillin clavulanate was commenced. In the following two days he developed coughing, severe dysphagia and vomiting, and was admitted to a general hospital. Due to pulmonary crackles ciprofloxacin therapy was added. Mycophenolate mofetil was stopped. Because his condition did not improve within 48 hours and acute allograft injury was observed, the patient was transferred to the university hospital. He developed a maculopapular rash (Figure 1) and severe stomatitis (Figure 2). Dysphagia, excessive salivation and vomiting required parenteral nutrition and fluid replacement. Skin biopsy showing folliculitis was suggestive for infection (Figure 3). Chest x-ray, urinalysis and graft sonography were unremarkable. Laboratory analysis showed leukocytosis (16.9 cmm, 88% neutrophils, 4.7% lymphocytes), elevated CRP (18.2 mg/dL, normal < 0.5 mg/dL) and serum creatinine (1.5 mg/dL). Procalcitonin, liver, thyroid parameters, blood cultures as well as a smear test from a mouth lesion were negative. He also tested negative for active HIV, CMV, EBV, HSV, VZV, Parvo B19 and hepatitis infection. PCR of serum for target virus revealed viremia. Appropriate treatment was administered and the patient responded with resolution of fever, rash, stomatitis and renal dysfunction.

  • S. Reuter*, M. A. Schlüter, H. Pavenstädt and B. Suwelack

  • Department of Internal Medicine D, General Internal Medicine and Nephrology,

  • University Hospital of Münster, Münster, Germany

  • *Corresponding author: Stefan Reuter,


Figure 1. Maculopapular rash.

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Figure 2. Stomatitis.

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Figure 3. Periodic acid Schiff stain of a skin biopsy revealed inflammatory cells, mainly lymphocytes, macrophages and neutrophils. Inflammation can be observed perivascular, and within the infundibulum and wall of the hair follicle. Besides, an interstitial inflammation including extravasation of erythrocytes was found.

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  1. Top of page
  2. Questions
  1. Based on the skin lesion and biopsy, what is the most likely diagnosis?
    1. Pemphigus vulgaris
    2. Cytomegalovirus
    3. Human herpes virus 6
    4. Epstein Barr virus
    5. Disseminated herpes zoster
  2. Which clinical manifestation(s) of the following is/are the most common in HHV6-infected solid organ transplant recipients?
    1. Fever
    2. Hepatitis
    3. Encephalitis
    4. Pneumonitis
    5. All manifestations can be frequently observed
  3. What antiviral therapy can be recommended to treat HHV6 disease?
    1. PEG interferon
    2. Ganciclovir, foscarnet or cidofovir
    3. Sirolimus
    4. Acyclovir
    5. Everolimus
  4. What are common differential diagnoses of aphthous stomatitis in transplantation?
    1. Cytomegalovirus
    2. Herpes simplex infection
    3. Ulcer related to sirolimus use
    4. Adverse effect of mycophenolate mofetil
    5. All of the above
  5. Which of the following is FALSE regarding aphthous stomatitis?
    1. Herpes simplex infection is the predominant cause of aphthous stomatitis
    2. Ulcers usually heal in 7–14 days
    3. The cause of aphthous stomatitis remains unknown
    4. Stress, infections or trauma can lead to aphthous stomatitis
    5. Aphthous stomatitis is a diagnosis of exclusion

To complete this activity and earn credit, please go to