J. K. L. Tan, MD, FRCPC

Department of Medicine, University of Western Ontario, London, ON, Canada
Windsor Regional Hospital, Windsor, ON, Canada


Acne that is recalcitrant to therapy is a common clinical dilemma. Some of the influencing factors that contribute to treatment challenges include poor adherence, inadequate therapy, and diagnostic mimics.

Diagnostic Considerations

Acne is a common, yet complex skin disorder of the pilosebaceous units that is especially prevalent among people aged 15-24 years, and the associated psychosocial impact can be significant. Acne severity may be classified as minimal, mild, moderate and severe based on the presence of primary acne lesion types, their distribution, and the density of involvement.
All forms of acne involve 1 or more of the following pathophysiologic factors:

  • hyperkeratinization of the follicular epithelium with comedone formation
  • sebaceous gland hyperfunction with increased sebum production
  • proliferation of Propionibacterum acnes (P. acnes)
  • local immune hypersensitivity causing inflammation

Therapeutic Options

Existing therapies for acne can be divided into 3 categories:

  1. Conventional therapies include topical retinoids, antibiotics, benzoyl peroxide (BP), systemic antibiotics, hormonal therapy, and oral isotretinoin. Treatment selection is based on the predominant acne lesion type and overall acne severity. Comedones are most effectively addressed by the comedolytic effect of retinoids. The role of P. acnes in inflammatory papules/pustules is the rationale for using topical/oral antibiotics and BP agents. Hormonal therapy reduces sebum secretion, secondarily reducing P. acnes. Oral isotretinoin affects all pathogenic factors and is the treatment standard for severe or recalitrant acne. Concerns with P. acnes resistance to antibiotics can be addressed by avoiding antibiotic monotherapy, using antibiotics in combination with BP, and avoiding oral antibiotics used for community-acquired infections.
  2. Procedural modalities include comedone extraction, intralesional steroid injections, microdermabrasion, and chemical peels.
  3. Optical modalities include laser treatment, noncoherent light sources, and photodynamic therapy.

Management of Recalcitrant Acne - imageTop

Improving Patient Adherence

Adherence can be directly influenced by the patient-physician relationship and treatment-related issues.1 More frequent follow-up, ongoing counselling and education can promote adherence, minimize complications, and improve outcomes. Encourage discussion of the impact of acne and gauge the patient’s treatment expectations to ensure that their perspective is heard. Tips for encouraging adherence1 include:

  • Reassure patients that acne is a very common skin condition caused by a combination of variables including genetics, hormones, and stress, and it is aggravated by occlusive factors. It is not a result of poor hygiene.
  • Explain the pathogenic features of acne and the rationale for the selected treatment regimen. Provide printed material that will educate and reinforce the aims of therapy and the importance of adherence.
  • Detail potential side-effects for the medications, modifying the dosing schedule or switching treatments based on tolerance and patient preference.

Management of Recalcitrant Acne - imageTop

Clinic Visits

After the initial visit, plan to see patients again at 4 weeks to review medications (i.e., where and how to apply them and how long to use them), encourage maintenance therapy, and counsel patients to expect improvement in 8-10 weeks. By 8-10 weeks, if a patient’s acne has not improved, either because the number of lesions has increased or due to patient dissatisfaction with the treatment, evaluate other options.

Management of Recalcitrant Acne - imageTop

Acne Mimics

There are multiple factors that engender recalcitrant acne. The primary differentiating feature of acne mimics from acne is the absence of comedones. However, some of these conditions may appear coincidentally with acne, particularly when there has been previous antibiotic therapy for acne.

Skin DisorderComments
(also referred
as sweat rash or
prickly heat)
  • Develops from eccrine gland occlusion; can result in extensive minute translucent papules (miliaria), which can become inflamed, leading to inflammatory non-follicular papules (miliaria rubra).
  • Triggering factors include high ambient heat/humidity, occlusive moisturizers, make-up, hair grooming products, clothing, and headwear. Commonly affects the forehead and hairline.
  • Can present as extensive, studded, noninflammatory micropapules, and inflammatory papules. These lesions are not centered around a pilosebaceous unit.
  • To treat, reduce environmental heat and humidity and local aggravating factors. Miliaria rubra will respond to topical therapy with an astringent effect, e.g., gel-based BP preparations.
  • Results from perifollicular inflammation caused by Demodex folliculorum, an otherwise ubiquitous pilososebaceous parasitic resident mite that feeds on sebum and the stratum corneum.
  • Typically affects an older population than does acne vulgaris.
  • Follicular papules/pustules exhibit more diffuse background erythema. Comedones are absent.
  • May also mimic inflammatory rosacea.
  • Laboratory testing includes a non-invasive skin surface biopsy using cyanoacrylate adhesive and microscope examination; a density of =5 mites/cm2 of skin surface indicates infestation.2
  • Treatment includes topical metronidazole or permethrin. Oral ivermectin 0.2mg/kg q.wk. for 2-4 weeks may help in more extensive or resistant cases.
  • Triggered by the lipophilic yeast Malassezia furfur. Extension deep into the pilosebaceous follicle is considered to be the cardinal feature.3
  • Typically affects regions rich in sebaceous glands (i.e., scalp, face, upper torso).
  • Many of the factors aggravating acne and miliaria, e.g., higher sebum production and occlusion, can be triggers. Prolonged antibiotic therapy and immunosupression may also aggravate it.
  • Presentation is either asymptomatic or seen as itchy, follicular, typically monomorphic papules/pustules in the absence of comedones.
  • Laboratory evaluation is based on microscopic examination of pustule contents for hyphae and spores (appearing like a spaghetti and meatballs pattern). Skin biopsies may help if pustules are not present.
  • To treat, correct triggering factors where possible. For milder cases, topical antifungal agents may be adequate (e.g., azole or selenium sulfide, which are formulated in foams, shampoos, lotions).
  • For more extensive or resistant cases, up to 8 weeks of systemic therapy may be needed, e.g., itraconazole 200mg once weekly; ketoconazole 200mg b.i.d. once weekly; or fluconazole 150mg once weekly.
Gram Negative
  • A pilosebaceous unit infection caused by gram-negative organisms.
  • Patients may present with inflammatory acne unresponsive to antibiotics or previously responsive acne that subsequently worsens.
  • May be seen as monomorphic papules/pustules or deep indurated nodules and cysts especially on cheeks and chin.
  • Laboratory confirmation requires bacterial culture of pustules.
  • Bacteria involved may be Klebsiella, Serratia, Escherischia or Proteus species. Pseudomonas is more frequently involved with hot tub folliculitis.
  • For milder cases use topical therapy with BP; for extensive involvement or in the presence of nodules and cysts use oral isotretinoin.4

Management of Recalcitrant Acne - imageTop

Diagnostic Procedures for Acne Mimics

Diagnosis can be guided by the morphology of the lesions and confirmed through appropriate testing.

  • Pustules: bacterial culture; microscopy of pustules with 10%-20% KOH to evaluate for Malasezzia
  • Papules: cyanoacrylate skin surface biopsy to evaluate for Demodex; punch biopsy to evaluate for Malasezzia
  • Nodules and cysts: bacterial culture; punch biopsy for Malasezzia
  • Hormonal testing for polycystic ovarian syndrome (testosterone, DHEA-S, LH, FSH, androstenedione), and congenital adrenal hyperplasia (cosyntropin stimulation and 17-hydroxyprogesterone levels)

Management of Recalcitrant Acne - imageTop


Acne treatment success involves a comprehensive approach that addresses diagnostic confounders, appropriate therapeutic options and patient adherence. Ongoing education and counselling will assist in meeting patient expectations and establishing a favourable rapport that promotes adherence. A possible contributing factor for inadequate response to acne therapy may be the misdiagnosis or coexistence of other skin disorders that resemble acne. Confirmation of these concurrent conditions with the aid of laboratory evaluations and the withdrawal of triggering factors can mitigate the effects of recalcitrant disease.


  1. Vender RB. Skin Therapy Lett FP 4(2):1-3 (2008 May).
  2. Kulac M, et al. Int J of Dermatol 47(1):72-7 (2008 Jan).
  3. Ayers K, et al. Arch Pediatr Adolesc Med 159(1):64-7 (2005 Jan).
  4. Boni R, et al. Am J Clin Dermatol 4(4):273-6 (2003).