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Grade 1 - Mild

General Recommendation

Early intervention is important; treatment of Papules or Pustules with a topical antibiotic may help to mitigate lesion severity.

Treatment

Topical antibiotics, such as metronidazole cream, clindamycin or erythromycin, used twice-daily or as needed.1,2 Metronidazole is preferred (as a 2% preparation in cetomacrogol cream or as 0.75% topical cream) because of its mildness, as it is normally used for the very sensitive skin of Rosacea patients.2 Topical anti-acne agents such as erythromycin, clindamycin and benzoyl peroxide are effective but much more aggressive as they are meant for young, resilient, acne-affected skin.2

The use of topical steroids is controversial. Steroids are advised by some authors3 while others state that they should be avoided on the face and trunk as the possible risks (induction of steroidal Rosacea or acne, atrophy, Telangiectasia, chronic abuse with tachyphylaxis and steroid dependence) outweigh the advantages.2

Products

  • Metronidazole 2.0% preparation in cetomacrogol cream, or 0.75% topical cream.
  • Clindamycin 1%.
  • Erythromycin 4%.

EGFRI Treatment

Continue with/withold the selected EGFRI-treatment regimen, as recommended in the current and relevant SmPC and according to the patient’s condition.4,5,6,7,8

Grade 2 – Moderate

General Recommendation

Oral antibiotics, and more specifically tetracyclines, should be used for moderate acneiform eruption.1 The initiation of oral tetracyclines is mostly based on clinical judgement (insufficient response to topical metronidazole, extensive disease).9

Treatment

The preferred type of tetracycline may vary. Minocycline 100 mg qd is probably most effective because of its high penetration in the Pilosebaceous unit. It is however avoided by some because of the rare occurrence of drug-induced lupus, hepatitis or hyperpigmentation.9 Doxycycline 100 mg qd (which may cause photosensitivity) or lymecycline 300 mg qd are alternatives. Like metronidazole, tetracyclines are not administered for their antibiotic properties but rather for their anti-inflammatory properties; usually they are given for several months.9
If superinfection with Staphylococcus aureus occurs, a penicillinase-resistant penicillin (eg flucloxacillin 500 mg tid) or cephalosporin (eg cefuroxime axetil 500 mg bid) may be added for 5 days (tetracyclines are rarely active against S. aureus9). Generally a swab is also taken and screened to generate an antibiotic sensitivity profile, so that the antibiotic can be switched appropriately in case of resistance.9

Products

  • Minocycline 100 mg qd.
  • Doxycycline 100 mg qd.
  • Lymecycline 300 mg qd.
  • Flucloxacillin 500 mg tid.
  • Cefuroxime axetil 500 mg bid.

EGFRI Treatment

Continue with/withold the selected EGFRI-treatment regimen, as recommended in the current and relevant SmPC and according to the patient’s condition. 4,5,6,7,8

Grade 3 - Severe

General Recommendation

For severe acneiform eruptions, dermatological treatment as used in moderate rash is intensified.

Treatment

In the case of severe rash with numerous or confluent Pustules and extensive Exudation, the tetracycline dose is doubled until the severity reduces to ‘moderate’.

For marked oedema, saline compresses (lasting 15 minutes, 2-3 compresses three times a day) are very helpful for rapid clearance of the inflammation. As compresses dry out the skin very effectively, they should only be applied for a limited period of time (eg a few days) and each application should be followed by repeated application of metronidazole cream.2

In the case of superinfection with Staphylococcus aureus, a penicillinase-resistant penicillin (eg flucloxacillin 500 mg tid) or cephalosporin (eg cefuroxime axetil 500 mg bid) may be added for 5 days (tetracyclines are rarely active against S. aureus9). Generally a swab is also taken and screened to generate an antibiotic sensitivity profile, so that the antibiotic can be switched appropriately in case of resistance.2

Although oral isotretinoin has been shown to be effective for EGFRI-induced acneiform eruption,10 its use is not recommended due to concern about its possible effects on EGFRI activity and the overlapping side-effect profile (Xerosis, sensitivity for S. aureus superinfection, Paronychia, Pyogenic granuloma), which may lower tolerability.2

Products

  • Minocycline 100 mg bid.
  • Doxycycline 100 mg bid.
  • Lymecycline 300 mg bid.
  • Flucloxacillin 500 mg tid.
  • Cefuroxime axetil 500 mg bid.

EGFRI Treatment

Withhold EGFRI treatment; continue with the selected EGFRI-treatment regimen only if rash grade ≤2. Continue with/withold the selected EGFRI-treatment regimen, as recommended in the current and relevant SmPC and according to the patient’s condition.4,5,6,7,8

References

1Tan EH & Chan A. Ann Pharmacother 2009; 43: 1658-1666.
2Segaert S. Targeted Oncol 2008; 3: 245-251.
3Lynch TJ, Jr. et al. Oncologist 2007; 12: 610-621.
4European Medicine Agency. Tarceva® (erlotinib) Summary of Product Characteristics 2009.
5European Medicine Agency. Iressa® (gefitinib) Summary of Product Characteristics 2009.
6European Medicine Agency. Erbitux® (cetuximab) Summary of Product Characteristics 2009.
7European Medicine Agency. Vectibix® (panitumumab) Summary of Product Characteristics 2009.
8European Medicine Agency. Tyverb® (lapatinib) Summary of Product Characteristics 2010.
9Segaert S et al. Eur J Cancer 2009; 45(Suppl 1): 295-308.
10Gutzmer R et al. Hautarzt 2006; 57: 509-513.

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