Skin Changes - Papulopustular Rash

Definition

Papulopustular rash is also referred to as acneiform rash, acne-like rash or folliculitis.1 This kind of eruption has also been well described with EGFR inhibitors, and is more or less confined to the seborrheic areas (areas rich in sebaceous glands): the face (especially the nose, the cheeks, the forehead and the chin), the scalp, the neck and retroauricular area, the shoulders and the upper trunk (typically V-shaped reflecting the density of the sebaceous glands in that skin area). Sometimes the lower parts of the back, the abdomen, the buttocks and even the arms and legs can be involved as well, whereas the palms of hands and soles of feet (containing no hair follicles) are spared.1-3

Incidence

Rash, which includes papulopustular rash, is reported in up to 53% of patient treated with vandetanib.4-5 Papulopustular rash is not reported with the other multikinase inhibitors discussed on this website.

Pathological Features

Papulopustular skin lesions have an early infiltration with T-lymphocytes, followed by a hyperkeratotic, ectatic appearance of the follicular infundibula and a florid, neutrophilic suppurative infiltrate.3 As a result, the most common picture is that of perifolliculitis and neutrophilic folliculitis. The pustules are notably sterile with negative cultures or staining for bacteria, fungi, yeasts (including Malassezia furfur) or Demodex mites.3

Onset

Vandetanib-associated rash is reported to start within 1-2 weeks following treatment initiation and gradually subsides over a few months.

Resolution

The incidence of rash is reduced in subsequent cycles. Also see management of Papulopustular rash

Grading and Lesion Characteristics

According to the NCI-CTCAE V4.03,6 papulopustular rash is defined as, “A disorder characterised by a rash consisting of papules (a small, raised pimple) and pustules (a small pus filled blister), typically appearing in face, scalp, and upper chest and back. Unlike acne, this rash does not present with whiteheads or blackheads, and can be symptomatic, with itchy or tender lesions.” However, grading of papulopustular rash according to the NCI-CTCAE V4.03 criteria is problematic as the percentage of the affected area needs to be expressed as a percentage compared to the whole body surface area (BSA). An alternate option for grading papulopustular rash is by the Multinational Association of Supportive Care in Cancer (MASCC) EGFR Inhibitor Skin Toxicity Tool (MESTT)7, which allows for more detailed reporting of rash.

Grade 1 (mild) Rash

  • The NCI-CTCAE v4.03 definition for grade 1 acneiform rash reads: Papules and/or Pustules covering <10% BSA, which may or may not be associated with symptoms of pruritus or tenderness.
  • The MESTT definition of grade 1A papulopustular rash reads: Papules or pustules < 5; OR area of erythema or oedema < 1cm in size; NO pain, pruritus, effect on emotions or functioning.
  • The MESTT definition of grade 1B papulopustular rash reads: Papules or pustules > 5; OR area of erythema or oedema <1cm in size AND mild pain or pruritus OR effect on emotions or functioning.

Grade 2 (moderate) Rash

  • The corresponding NCI-CTCAE v4.03 definition for grade 2 acneiform rash reads: Papules and/or Pustules covering 10-30% BSA, which may or may not be associated with symptoms of Pruritus or tenderness; associated with psychosocial impact; limiting instrumental activities of daily living (ADL: refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money etc.). The example shown demonstrates how the rash in this patient could be perceived to be grade 1 rash according to NCI-CTCAE V4.03 criteria based on the extent of the rash on the face; however, the extent of the rash on the whole body needs to be considered which in this example warrants allocation of a grade 2 rash.
  • The MESTT definition of grade 2A papulopustular rash reads: Papules or pustules 6-20; OR more than 1 area of erythema or oedema <1cm in size; AND no pain, pruritus, effect on emotions or functioning.
  • The MESTT definition of grade 2B papulopustular rash reads: Papules or pustules 6-20; OR more than 1 area of erythema or oedema <1cm in size; AND pain, pruritus, effect on emotions or functioning.

Grade 3/4 (Severe) Rash

  • The NCI-CTCAE v4.03 definition for grade 3 acneiform rash reads: Papules and/or Pustules covering >30% BSA, which may or may not be associated with symptoms of Pruritus or tenderness; limiting self-care ADL (refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not confined to bed); associated with local superinfection with oral antibiotics indicated.
  • The MESTT definition of grade 3A papulopustular rash reads: Papules or pustules >30; OR more than 5 areas of erythema or oedema <1cm in size; AND no pain, pruritus, effect on emotions or functioning.
  • The MESTT definition of grade 3B papulopustular rash reads: Papules or pustules >30; OR more than 5 areas of erythema or oedema <1cm in size; AND pain, pruritus, effect on emotions or functioning; papules or pustules extending beyond head, chest or back.
  • The NCI-CTCAE v4.03 definition for the extremely rare grade 4 acneiform rash reads: Papules and/or Pustules covering any % BSA, which may or may not be associated with symptoms of Pruritus or tenderness and are associated with extensive superinfection with intravenous (i.v.) antibiotics indicated; life-threatening consequences.

Papulopustular Rash by grade

References

1Widakowich C. Review: side effects of approved molecular targeted therapies in solid cancers. Oncologist. 2007;12;1443-1455.
2Lacouture ME. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer. 2011;19:1079–1095.
3Segaert S, et al. Skin toxicities of targeted therapies. Eur J Cancer. 2009;45:295-308.
4European Medicines Agency. Caprelsa® (vandetanib) Summary of Product Characteristics 2014.
5Food and Drug Administration. Caprelsa® (vandetanib) Prescribing Information 2014.
6National Cancer Institute Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events and Common Toxicity Criteria [v4.03]. 15-12-2010. Date accessed 22 August 2014.
7Multinational Association of Supportive Care in Cancer (MASCC) EGFR Inhibitor Skin Toxicity Tool (MESTT) (accessed 22 August 2014)

Last update: 22 August 2014