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Observation |

Cyclosporine-Induced Infantile Nodulocystic Acne FREE

Jamison E. Strahan, MD; Joanna M. Burch, MD
[+] Author Affiliations

Author Affiliations: Departments of Dermatology and Pediatric Dermatology, The Children's Hospital, Aurora, Colorado.


Arch Dermatol. 2009;145(7):797-799. doi:10.1001/archdermatol.2009.98.
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Background  In adult organ transplant recipients, nodulocystic acne induced by the use of cyclosporine can be treated successfully with isotretinoin. Cyclosporine's acnegenic effects in children and the pediatric response to treatment are less clear.

Observations  A 9-month-old boy presented with cysts and nodules on his face after he began cyclosporine therapy after a heart transplantation. We describe successful treatment with cessation of cyclosporine therapy and administration of isotretinoin.

Conclusions  Nodulocystic acne may be induced by the use of cyclosporine in children as well as adults. When it occurs, it can be managed with cessation of cyclosporine therapy and treatment with isotretinoin. Because this management approach may influence other outcomes in children with transplants, it is best to treat these patients using a multidisciplinary approach.

Figures in this Article

Infantile acne, which often presents within the first 6 months of life and resolves spontaneously,1 is most commonly associated with fluctuations in circulating androgens that stabilize during the initial maturation of the adrenal gland.2 When prepubertal acne is persistent or nodulocystic, the clinician should consider other causes, such as hormonal aberrations (including tumors and hyperplasias), toxin exposures, and medications, including comedogenic topical products.

Pediatric organ transplant recipients are routinely maintained on a regimen of immunosuppressants, many of which have cutaneous adverse effects. One of the largest series to date that examined cutaneous adverse events in pediatric organ transplant recipients reported that all 145 children who received corticosteroids or cyclosporine had dermatologic adverse effects, including stria, acne, hypertrichosis, gingival hyperplasia, and cutaneous infections.3 We describe an infant with cyclosporine-induced nodulocystic acne that resolved after cessation of cyclosporine therapy and administration of isotretinoin.

A 9-month-old boy presented for evaluation of a new facial rash. He had a 6-week history of large red bumps on his cheeks that were tender, slow growing, and intermittently draining a yellowish fluid. His health was otherwise stable, with no evidence of lethargy, no change in eating habits, and normal development. Cultures of draining fluid were negative for bacteria, acid-fast bacilli, and fungi. Separate courses of oral cephalexin and trimethoprim-sulfamethoxazole failed to result in improvment.

The patient's medical history was remarkable for left hypoplastic heart syndrome, status post heart transplantation at 2 weeks of age. He had been maintained on a regimen of immunosuppressants (cyclosporine and azathioprine) since the transplantation but had not received systemic corticosteroids. His cardiovascular profile was stable according to routine echocardiograms, and cyclosporine levels were consistently within a therapeutic range.

Physical examination revealed multiple erythematous, fluctuant, tender cysts and nodules over both cheeks, with adjacent multiple smaller folliculocentric papules and pustules (Figure, A). The patient had no virilizing features with respect to hair growth, body habitus, or genitalia. A punch biopsy specimen showed a chronic deep folliculitis with abscess formation. Periodic acid–Schiff with diastase and acid-fast bacillus stains were negative for fungal elements and mycobacteria, respectively. Tissue cultures showed only normal bacterial flora. Serum dehydroepiandrosterone sulfate and free testosterone levels were within normal limits. The patient underwent congenital adrenal hyperplasia screening at birth and at 2 weeks of life, with a normal serum 17-hydroxyprogesterone concentration; no additional endocrine studies were performed.

Place holder to copy figure label and caption
Figure.

Clinical photograph of acne before treatment (A), after 1 month of treatment (B), and after 5 months of treatment (C) with isotretinoin.

Graphic Jump Location

A diagnosis of nodulocystic acne due to cyclosporine therapy was made. After we discussed the case with the transplantation team, the cyclosporine therapy was discontinued and tacrolimus therapy was initiated. Isotretinoin therapy (0.5 mg/kg) was initiated comcomitantly; 10-mg capsules were lanced and mixed into chocolate pudding for oral administration every other day. With the aim of aggressive treatment to lessen scarring potential, a brief course of oral corticosteroids (prednisolone phosphate, 1 mg/kg/d) was also administered during the first month of isotretinoin therapy. The patient's acne dramatically improved within the first 24 to 72 hours after the cyclosporine therapy was discontinued, and he showed continued improvement during the isotretinoin therapy (Figure, B and C). He completed a 5-month course of isotretinoin, for a cumulative dose of 114 mg/kg. The results of his blood work were coordinated with his transplantation team to minimize venipuncture episodes on a monthly basis. With the exception of a transient leukopenia (from 5500 to 3300 cells per microliter) that resolved after the first month of treatment, his blood indexes (including a complete blood cell count with differential, a comprehensive metabolic panel, and a fasting lipid profile) were normal throughout treatment. His course was complicated by xerosis and retinoid dermatitis, which was treated effectively with topical fluocinolone acetonide, twice daily as needed.

Cyclosporine, which is an inhibitor of T-lymphocyte activation that is used routinely during the management of solid organ transplants, can cause a variety of cutaneous adverse reactions. One study of 67 adult renal transplant recipients who were treated with cyclosporine showed that most of the cutaneous adverse effects involved the pilosebaceous unit: hypertrichosis (60%), epidermal cysts (28%), keratosis pilaris (21%), acne (15%), folliculitis (12%), and sebaceous hyperplasia (10%).4 In vitro studies have suggested that follicular epithelium is more sensitive to the growth-promoting effects of cyclosporine than are interfollicular keratinocytes.5

The first cases suggesting an association between cyclosporine and nodulocystic acne were reported in the late 1980s and early 1990s.69 Most reports describe adult patients with heart and renal transplants who developed nodulocystic acne and were treated successfully with isotretinoin. However, some patients have improved with cessation of cyclosporine therapy alone.10 While an association between cyclosporine use and acne now appears clear, causality remains to be established, particularly given the lack of reported rechallenges with cyclosporine.

Whether children develop similar cutaneous reactions from cyclosporine use as adults is not completely clear. Hypertrichosis and gingival hyperplasia represent most dermatologic complaints in the pediatric population. One small series reported that all cyclosporine-treated pediatric renal transplant recipients had cutaneous adverse effects, mostly hypertrichosis.11 Another study showed that gingival hyperplasia occurred more frequently in children than in adults.12 Age may alter the manifestation of these reactions. For example, one series demonstrated that younger children had more severe adverse effects than older children.3 The same series showed that acne tended to occur in older children, with no cases of acne in patients younger than 2 years. Because infants were underrepresented in all of these series, it is difficult to assess their true risk of cyclosporine-induced adverse effects.

Regardless of association with cyclosporine use, infantile nodulocystic acne should be treated aggressively. Isotretinoin has demonstrated success in the treatment of nodulocystic infantile acne.13 It should be noted that multiple interventions were undertaken simultaneously for our patient (cessation of cyclosporine therapy, initiation of isotretinoin therapy, and administration of a short burst of prednisone), and it is unclear which one contributed most to his improvement.

When contemplating treatment with systemic retinoids for similar patients, health care providers should recognize that transplant recipients may be at risk for unique adverse events, such as graft rejection and disrupted bone growth. Studies examining retinoid effects on graft rejection show mixed observations, with some suggesting detriment and others suggesting benefit.1416 Regarding effects on bone, transplant recipients may have a higher risk of adverse effects because of several contributing factors, such as administration of systemic corticosteroids, prolonged bed rest, and frequent hospitalizations. While retinoid use has been associated with adverse effects on bone in children, most data are retrospective and involve long-term therapy with etretinate for disorders of keratinization.17 Other case reports document long-term use with no adverse bone effects.18 Therefore, the potential for disrupted bone metabolism in the transplant population is unclear, and the dermatologist should work with the transplant team to detect and manage these events.

In summary, we present a pediatric case of cyclosporine-induced nodulocystic acne that was successfully treated with cessation of cyclosporine therapy and a 5-month course of isotretinoin (114 mg/kg). Isotretinoin capsules can be lanced and mixed with food for ease of administration to infants. Our patient remains acne-free 8 months after the completion of isotretinoin therapy and on an alternative effective immunosuppressive regimen. This case illustrates the importance of a multidisciplinary approach when managing severe medication-induced cutaneous adverse effects.

Correspondence: Jamison E. Strahan, MD, Department of Dermatology, The Children's Hospital, 1665 N Ursula St, Aurora, CO 80045 (Jamison.Strahan@ucdenver.edu).

Accepted for Publication: October 20, 2008.

Author Contributions: Both authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Strahan and Burch. Analysis and interpretation of data: Strahan and Burch. Drafting of the manuscript: Strahan. Critical revision of the manuscript for important intellectual content: Burch. Study supervision: Burch.

Financial Disclosure: None reported.

Mann  MWEllis  SSMallory  SB Infantile acne as the initial sign of an adrenocortical tumor. J Am Acad Dermatol 2007;56 (2) (suppl)S15- S18
PubMed
Lucky  AW A review of infantile and pediatric acne. Dermatology 1998;196 (1) 95- 97
PubMed
Euvrard  SKanitakis  JCochat  PCambazard  FClaudy  A Skin diseases in children with organ transplants. J Am Acad Dermatol 2001;44 (6) 932- 939
PubMed
Bencini  PLMontagnino  GSala  Fde Vecchi  ACrosti  CTarantino  A Cutaneous lesions in 67 cyclosporine-treated renal transplant recipients. Dermatologica 1986;172 (1) 24- 30
PubMed
Takahashi  TKamimura  A Cyclosporin A promotes hair epithelial cell proliferation and modulates protein kinase C expression and translocation in hair epithelial cells. J Invest Dermatol 2001;117 (3) 605- 611
PubMed
Bunker  CBRustin  MHDowd  PM Isotretinoin treatment of severe acne in posttransplant patients taking cyclosporine. J Am Acad Dermatol 1990;22 (4) 693- 694
PubMed
Abel  EA Isotretinoin treatment of severe cystic acne in a heart transplant patient receiving cyclosporine: consideration of drug interactions. J Am Acad Dermatol 1991;24 (3) 511
PubMed
Marcusson  JATydén  G Acne conglobata in transplant patients treated with isotretinoin. Br J Dermatol 1988;118 (2) 310- 312
PubMed
Tam  MCooper  A The use of isotretinoin in a renal transplant patient with acne. Br J Dermatol 1987;116 (3) 463
PubMed
el-Shahawy  MAGadallah  MFMassry  SG Acne: a potential side effect of cyclosporine A therapy. Nephron 1996;72 (4) 679- 682
PubMed
Halpert  ETunnessen  WW  JrFivush  BCase  B Cutaneous lesions associated with cyclosporine therapy in pediatric renal transplant recipients. J Pediatr 1991;119 (3) 489- 491
PubMed
Menni  SBeretta  DPiccinno  RGhio  L Cutaneous and oral lesions in 32 children after renal transplantation. Pediatr Dermatol 1991;8 (3) 194- 198
PubMed
Barnes  CJEichenfield  LFLee  JCunningham  BB A practical approach for the use of oral isotretinoin for infantile acne. Pediatr Dermatol 2005;22 (2) 166- 169
PubMed
Floersheim  GLBollag  W Accelerated rejection of skin homografts by vitamin A acid. Transplantation 1972;14 (5) 564- 567
PubMed
McKerrow  KJMackie  RMLesko  MJPearson  C The effects of oral retinoid therapy on the normal human immune system. Br J Dermatol 1988;119 (3) 313- 320
PubMed
Chen  KCraig  JCShumack  S Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials. Br J Dermatol 2005;152 (3) 518- 523
PubMed
Halkier-Sørensen  LLaurberg  GAndresen  J Bone changes in children on long-term treatment with etretinate. J Am Acad Dermatol 1987;16 (5, pt 1) 999- 1006
PubMed
Paige  DGJudge  MRShaw  DGAtherton  DJHarper  JI Bone changes and their significance in children with ichthyosis on long-term etretinate therapy. Br J Dermatol 1992;127 (4) 387- 391
PubMed

Figures

Place holder to copy figure label and caption
Figure.

Clinical photograph of acne before treatment (A), after 1 month of treatment (B), and after 5 months of treatment (C) with isotretinoin.

Graphic Jump Location

Tables

References

Mann  MWEllis  SSMallory  SB Infantile acne as the initial sign of an adrenocortical tumor. J Am Acad Dermatol 2007;56 (2) (suppl)S15- S18
PubMed
Lucky  AW A review of infantile and pediatric acne. Dermatology 1998;196 (1) 95- 97
PubMed
Euvrard  SKanitakis  JCochat  PCambazard  FClaudy  A Skin diseases in children with organ transplants. J Am Acad Dermatol 2001;44 (6) 932- 939
PubMed
Bencini  PLMontagnino  GSala  Fde Vecchi  ACrosti  CTarantino  A Cutaneous lesions in 67 cyclosporine-treated renal transplant recipients. Dermatologica 1986;172 (1) 24- 30
PubMed
Takahashi  TKamimura  A Cyclosporin A promotes hair epithelial cell proliferation and modulates protein kinase C expression and translocation in hair epithelial cells. J Invest Dermatol 2001;117 (3) 605- 611
PubMed
Bunker  CBRustin  MHDowd  PM Isotretinoin treatment of severe acne in posttransplant patients taking cyclosporine. J Am Acad Dermatol 1990;22 (4) 693- 694
PubMed
Abel  EA Isotretinoin treatment of severe cystic acne in a heart transplant patient receiving cyclosporine: consideration of drug interactions. J Am Acad Dermatol 1991;24 (3) 511
PubMed
Marcusson  JATydén  G Acne conglobata in transplant patients treated with isotretinoin. Br J Dermatol 1988;118 (2) 310- 312
PubMed
Tam  MCooper  A The use of isotretinoin in a renal transplant patient with acne. Br J Dermatol 1987;116 (3) 463
PubMed
el-Shahawy  MAGadallah  MFMassry  SG Acne: a potential side effect of cyclosporine A therapy. Nephron 1996;72 (4) 679- 682
PubMed
Halpert  ETunnessen  WW  JrFivush  BCase  B Cutaneous lesions associated with cyclosporine therapy in pediatric renal transplant recipients. J Pediatr 1991;119 (3) 489- 491
PubMed
Menni  SBeretta  DPiccinno  RGhio  L Cutaneous and oral lesions in 32 children after renal transplantation. Pediatr Dermatol 1991;8 (3) 194- 198
PubMed
Barnes  CJEichenfield  LFLee  JCunningham  BB A practical approach for the use of oral isotretinoin for infantile acne. Pediatr Dermatol 2005;22 (2) 166- 169
PubMed
Floersheim  GLBollag  W Accelerated rejection of skin homografts by vitamin A acid. Transplantation 1972;14 (5) 564- 567
PubMed
McKerrow  KJMackie  RMLesko  MJPearson  C The effects of oral retinoid therapy on the normal human immune system. Br J Dermatol 1988;119 (3) 313- 320
PubMed
Chen  KCraig  JCShumack  S Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials. Br J Dermatol 2005;152 (3) 518- 523
PubMed
Halkier-Sørensen  LLaurberg  GAndresen  J Bone changes in children on long-term treatment with etretinate. J Am Acad Dermatol 1987;16 (5, pt 1) 999- 1006
PubMed
Paige  DGJudge  MRShaw  DGAtherton  DJHarper  JI Bone changes and their significance in children with ichthyosis on long-term etretinate therapy. Br J Dermatol 1992;127 (4) 387- 391
PubMed

Correspondence

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