Successful treatment of acne with isotretinoin in chronic granulomatous disease

ARTICLE

Auteur(s) : Egidio BARBI¹, Irene BERTI², Marta MINUTE² martaminute@gmail.com, Floriana ZENNARO³

¹ Pediatria d’Urgenza, IRCCS Burlo Garofolo, University of Trieste, Italy

² Clinica Pediatrica, IRCCS Burlo Garofolo, University of Trieste, Italy

³ Radiology Department, IRCCS Burlo Garofolo, University of Trieste, Italy

Chronic granulomatous disease (CGD) is an immune deficiency caused by different mutations of the gene that encodes for the enzyme dinucleotide phosphate oxidase, which regulates free oxygen radical production for the destruction of phagocytosed microorganisms. This deficiency results in recurrent and severe bacterial and fungal infections with formation of granulomas.

The most prevalent site of disease is the lungs, but the skin is often affected too. Cutaneous lesions can range from aseptic granulomas to classic abscesses; more than 7% of CGD patients suffer at least one episode of acne in their lifetime [1].

Acne is an inflammatory disease of the pilosebaceous unit, characterized by increased production of sebum on which commensal bacteria proliferate. Its treatment, when first line ones fail, is based on the use of isotretinoin (13cis-retinoic acid) [2]. Isotretinoin's efficacy is due to its anti-inflammatory properties and to the impact on the major aetiological factors implicated in acne (cell-cycle progression, cellular differentiation, cell survival and apoptosis). Isotretinoin results in a significant reduction in sebum production, thus influencing comedogenesis and lowering surface and ductal presence of P. acnes [3].

There are some concerns about isotretinoin use in CGD patients, because it may be associated with increased granulation tissue responses [4] and nasal carriage rates of Staphylococcus aureus [5]. However, acne is a major problem for these patients and a recent case report showed efficacy of isotretinoin therapy [6].

The patient was a 30-year-old man with X-linked CGD. He was diagnosed at one year of age with a NBT test, performed because of a Chron-like cholitis. His clinical history had been characterized by multiple granulomatous localizations which required antibiotic and anti-fungal treatments. The patient's treatment at the time of evaluation consisted of co-trimoxazol 800 mg daily, itraconazole 100 mg/day, amantadine 50 mg once a day, prednisone 5 mg and 10 mg on alternate days, folic acid.

The most relevant problems at the time were persistent face lesions, defined as acneic folliculitis, which were hardly and inconsistantly controlled with antibiotic therapy (during the last two years: azitromicin, ciprofloxacin, voriconazole, minociclyne and trimethoprim-sulfametoxazole).

These lesions appeared to be severe, as documented by a MR of the soft tissues of the head and neck (figures 1A, B), moderately painful, and were not only handicapping but also potentially dangerous for the risk of worsening involving deeper structures. Systemic isotretinoin (0.5 mg/kg/day) was started. The acne dramatically improved (figure 1C) without side effects, except for a mild feeling of dryness. Blood tests showed normal values of triglycerides, glucose, cholesterol and creatinine kinase; urinalysis was normal. Treatment was stopped after 3 months with benefits persisting in 4 months of follow up. To the best of our knowledge this is the second report in the literature about the efficacy of isotretinoic acid in CGD.

During isotretinoin therapy, antibiotic treatment was not changed (co-trymoxazole prophylaxis) as well as the patient's standard treatment. In this case, no abnormal granulation response, a possible side effect of isotretinoin, developed but we should consider that, according to cases reported in literature, therapy for this reaction includes prednisone, a drug that was already part of our patient's daily therapy and might have been protective. The same protective role might have been played by co-trymoxazole prophylaxis.

Since acne is a relevant and cumbersome problem for these patients we believe that the possibility of an efficacious and safe treatment is a major issue. More data are needed to establish the efficacy and safety of isotretinoin in CGD.

Disclosure

Financial support: none. Conflict of interest: none.

References

1 JM van den Berg, E van Koppen et al. Chronic granulomatous disease: the European experience PLoS One 2009; 4: e5234 [Epub 2009 Apr 21].

2 W. Burgdorf Skin diseases with high public health impact. Acne vulgaris Eur J Dermatol 2008; 18: 107-108.

3 A. Layton The use of isotretinoin in acne Dermatoendocrinol 2009; 1: 162-169.

4 J Henkes, C Ferrandiz, M Ribera, O Servitje, J. Peyri Nodular cystic acne: excessive granulation tissue caused by isotretinoin Med Cutan Ibero Lat Am 1987; 15: 55-58.

5 JJ Leyden, KJ McGinley, A.N. Foglia Qualitative and quantitative changes in cutaneous bacteria associated with systemic isotretinoin therapy for acne conglobata J Invest Dermatol 1986; 86: 390-393.

6 AP Spillane, C.M. Hivnor Isotretinoin use in a case of chronic granulomatous disease Pediatr Dermatol 2009; 26: 756-758.