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ATRA-induced scrotal ulcer
See also in: Anogenital
Other Resources UpToDate PubMed

ATRA-induced scrotal ulcer

See also in: Anogenital
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Contributors: John Barbieri, Misha A. Rosenbach MD, Noah Craft MD, PhD
Other Resources UpToDate PubMed


All-trans-retinoic acid (ATRA)-induced scrotal ulcers are a rare, self-limited complication of ATRA therapy. ATRA is a generally well-tolerated induction chemotherapeutic agent used for acute promyelocytic leukemia, leading to complete remission rates of approximately 90% in this specific subtype of leukemia. Although the pathophysiology of ATRA-induced scrotal ulcers is not fully understood, some have suggested that they may result from ATRA-induced release of cytokines and interleukins resulting in leukocyte activation and tissue damage. Some suspect that ATRA-induced scrotal ulcerations may be a localized form of a neutrophilic dermatosis, similar to a form of drug-induced Sweet syndrome.

Patients with ATRA-induced scrotal ulcers typically present with scrotal ulcerations 2-4 weeks after initiating treatment, but ulcers have been documented as early as 7 days after beginning ATRA induction therapy. These ulcerations are commonly associated with fever and leukocytosis. There is no clear age predominance, with cases reported in patients ranging in age from 8-63 years. The majority of cases in the literature involve Asiatic patients; however, there are case reports of white and African American patients as well.

Immunocompromised Patient Considerations:
In immunocompromised patients, an evaluation for an infectious etiology, such as herpes simplex virus or Cytomegalovirus (CMV), is critical before making a diagnosis of ATRA-induced scrotal ulcers.


N50.89 – Other specified disorders of the male genital organs

9750001 – Ulcer of scrotum

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Differential Diagnosis & Pitfalls

  • Pyoderma gangrenosum – ATRA therapy is also associated with the development of pyoderma gangrenosum, which can present with ulcerations that are similar in appearance. However, the ulcers of pyoderma gangrenosum are typically painful and involve the lower extremities or hands, rather than the scrotum. In addition, patients with pyoderma gangrenosum may exhibit pathergy, which is absent in ATRA-induced scrotal ulcers.
  • Sweet syndrome – Sweet syndrome may be associated with leukemia, and if patients are receiving granulocyte-stimulating factors post-chemotherapy, it can be a challenge to distinguish between Sweet syndrome and ATRA-induced ulcers. Sweet syndrome may also exhibit pathergy, and typically the lesions are more widespread; classic Sweet syndrome lesions will be edematous ("juicy") red plaques or nodules. While ulcerations can occur, they are not the most common lesion type.
  • Herpes simplex virus – Vesicles and ulcers are usually grouped and painful. There is often a past history of similar lesions.
  • Ecthyma – Superficial ulcerations with overlying gray-yellow crust. Gram stain and cultures will reveal gram-positive cocci. Most commonly found on shins, legs, or buttocks.
  • Candidiasis – Patients typically report pruritus and burning. Potassium hydroxide (KOH) preparation will show pseudohyphae and budding yeasts.
  • Behçet syndrome – Genital ulcers are painful and may be associated with epididymitis. Patients may exhibit pathergy. Oral ulcers are present.
  • Ecthyma gangrenosum – Acute onset of disseminated, painful hemorrhagic vesicles and bullae. Associated with Pseudomonas aeruginosa infections in immunocompromised patients. Note: Ecthyma gangrenosum in an immunocompromised patient constitutes a medical emergency.
  • Secondary syphilis – Skin manifestations are variable but most commonly include a diffuse, generalized papulosquamous eruption on the palms and soles.
  • Pemphigus vulgaris – Lesions common on mucosal surfaces. Look for Nikolsky sign (superficial layer of skin slips freely over deeper layers with lateral pressure).
  • Bullous pemphigoid – Tense bullae present on the abdomen, thighs, and forearms. Significant pruritus is often present.
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Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

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Last Updated: 02/16/2018
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ATRA-induced scrotal ulcer
See also in: Anogenital
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ATRA-induced scrotal ulcer : Painful skin lesions, Scrotum, Skin erosion, Skin ulcer
Clinical image of ATRA-induced scrotal ulcer
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