Pediatric Annals

An Adolescent Girl With Tuberous Sclerosis Complex and Acne

Jonette E Keri, MD, PhD; Nidhi Avashia

Abstract

DIAGNOSIS TSC with comorbid acne

DISCUSSION

This case represents an example where the patient actually had two conditions simultaneously. It is not unusual for patients with TSC to be treated for acne without the diagnosis of TSC ever being entertained In this case, the patient was aware of both conditions but was unable to differentiate between them.

The purpose of this case is to remind clinicians to look closely at facial lesions that are not classic acne or lesions that do not respond to traditional therapy, especially in patients with TSC or other genetic conditions that can have angiofibromas such as multiple endocrine neoplasia type 1 (MEN I).1 During her examination, the patient and her mother were educated on the types of lesions she had on her face. Specifically, she was given a mirror so that she could visualize the acneiform lesions to differentiate them from the adenoma sebaceum (angiofibromas) of TSC. This allowed for the patient to have realistic expectations for the results of treatment.

The patient was treated with aldapalene, a sodium sulfacetamide face wash, and a short-contact preparation (mask) of sulfur/sodium sulfacetamide. During the first 2 months of treatment, she also took a pulse dose of 5 days of azithromycin for menstrual acne flares. She received one treatment with the Blue Light (Dusa) for her acne. After 3 months, the patient noted moderate improvement. Laser treatments for adenoma sebaceum have been discussed, but the patient at this point prefers minimally invasive procedures.

TSC is a relatively common inherited disease. TSC is also known as Bourneville disease and epiloia (eg, epilepsy, low intelligence, angiofibroma), for the classic findings associated with TS. The prevalence is about 1 in 6,000.2 It is transmitted in an autosomal dominant fashion with variable penetrance. A large number (up to 50% to 75%) of cases represent spontaneous genetic mutations. Two genes have been isolated that give indistinguishable phenotypes, TSCl on chromosome 9q34 and TSC2 on chromosome 16pl3.3

Patients with TSC normally have a variety of physical findings in addition to the classic triad noted above. Adenoma sebaceum and ash leaf macules are the most common skin findings, occurring in almost 90% and 97% of patients, respectively.4 Adenoma sebaceum are angiofibromas and are located on the face as small symmetrical pink to brown papules of the cheeks, perinasal, and perioral regions. Ash-leaf macules are hypopigmented macules in the shape of a leaf. They may be singular or multiple, and solitary lesions are often seen in patients without TSC.4 Other dermatologie findings include confetti-like hypopigmented macules, shagreen patches, periungal fibromas (Koenen's tumors), café au lait spots, and skin tags.

Neurologic symptoms include mental deficiency (seen in 40% to 60% of patients), epilepsy (variable in its presentation), and neuropsychiatrie conditions such as attention-deficit disorder and autism.5 Other major system involvement includes cardiac rhabdomyomas, occurring in approximately 80% of infants with TSC.6 Renal manifestations most commonly include angiomyolipomas, at times growing large and sometimes leading to renal failure.7 Cystic disease of the kidneys can occur in patients with deletions of the TSC2 gene that extends to the nearby PKDl gene, which is responsible for polycystic kidney disease.8 Pulmonary involvement is more common in women, presenting in their 30s and can lead to respiratory failure.9 Ophthalmologic manifestations include retinal hamartomas, which can occur in half of patients but usually do not impair vision.10

Acne is the most common skin condition in the pediatrie population. Without close inspection, it is possible to misdiagnosis the patient as having acne when in fact the patient has angiofibromas, especially if the patient's diagnosis of TSC has been missed. Because this patient has an…

An 18-year-old girl presented with a previous diagnosis of tuberous sclerosis complex (TSC). At her initial visit to the dermatologist, she was using a nonprescription acne care regimen consisting of three steps. She was referred by her primary care physician because the lesions on her face were becoming of greater concern.

On physical exam, she had closed comedones over her forehead, a few larger cystic papules over her cheeks, and multiple 1- to 2-mm pinkish brown papules on her cheeks, perinasally and periorally.

Figure. Acneiform lesions are noted on the right cheek as a larger pink papule (arrow, top left) and on the upper forehead as closed comedones, or"whiteheads" (arrow, top right). Adenoma sebaceum (angiofìbromas) are noted as multiple small pink papules on the cheeks (bottom left), chin (bottom right), and periorifically around the nose and mouth.

Figure. Acneiform lesions are noted on the right cheek as a larger pink papule (arrow, top left) and on the upper forehead as closed comedones, or"whiteheads" (arrow, top right). Adenoma sebaceum (angiofìbromas) are noted as multiple small pink papules on the cheeks (bottom left), chin (bottom right), and periorifically around the nose and mouth.

DIAGNOSIS TSC with comorbid acne

DISCUSSION

This case represents an example where the patient actually had two conditions simultaneously. It is not unusual for patients with TSC to be treated for acne without the diagnosis of TSC ever being entertained In this case, the patient was aware of both conditions but was unable to differentiate between them.

The purpose of this case is to remind clinicians to look closely at facial lesions that are not classic acne or lesions that do not respond to traditional therapy, especially in patients with TSC or other genetic conditions that can have angiofibromas such as multiple endocrine neoplasia type 1 (MEN I).1 During her examination, the patient and her mother were educated on the types of lesions she had on her face. Specifically, she was given a mirror so that she could visualize the acneiform lesions to differentiate them from the adenoma sebaceum (angiofibromas) of TSC. This allowed for the patient to have realistic expectations for the results of treatment.

The patient was treated with aldapalene, a sodium sulfacetamide face wash, and a short-contact preparation (mask) of sulfur/sodium sulfacetamide. During the first 2 months of treatment, she also took a pulse dose of 5 days of azithromycin for menstrual acne flares. She received one treatment with the Blue Light (Dusa) for her acne. After 3 months, the patient noted moderate improvement. Laser treatments for adenoma sebaceum have been discussed, but the patient at this point prefers minimally invasive procedures.

TSC is a relatively common inherited disease. TSC is also known as Bourneville disease and epiloia (eg, epilepsy, low intelligence, angiofibroma), for the classic findings associated with TS. The prevalence is about 1 in 6,000.2 It is transmitted in an autosomal dominant fashion with variable penetrance. A large number (up to 50% to 75%) of cases represent spontaneous genetic mutations. Two genes have been isolated that give indistinguishable phenotypes, TSCl on chromosome 9q34 and TSC2 on chromosome 16pl3.3

Patients with TSC normally have a variety of physical findings in addition to the classic triad noted above. Adenoma sebaceum and ash leaf macules are the most common skin findings, occurring in almost 90% and 97% of patients, respectively.4 Adenoma sebaceum are angiofibromas and are located on the face as small symmetrical pink to brown papules of the cheeks, perinasal, and perioral regions. Ash-leaf macules are hypopigmented macules in the shape of a leaf. They may be singular or multiple, and solitary lesions are often seen in patients without TSC.4 Other dermatologie findings include confetti-like hypopigmented macules, shagreen patches, periungal fibromas (Koenen's tumors), café au lait spots, and skin tags.

Neurologic symptoms include mental deficiency (seen in 40% to 60% of patients), epilepsy (variable in its presentation), and neuropsychiatrie conditions such as attention-deficit disorder and autism.5 Other major system involvement includes cardiac rhabdomyomas, occurring in approximately 80% of infants with TSC.6 Renal manifestations most commonly include angiomyolipomas, at times growing large and sometimes leading to renal failure.7 Cystic disease of the kidneys can occur in patients with deletions of the TSC2 gene that extends to the nearby PKDl gene, which is responsible for polycystic kidney disease.8 Pulmonary involvement is more common in women, presenting in their 30s and can lead to respiratory failure.9 Ophthalmologic manifestations include retinal hamartomas, which can occur in half of patients but usually do not impair vision.10

Acne is the most common skin condition in the pediatrie population. Without close inspection, it is possible to misdiagnosis the patient as having acne when in fact the patient has angiofibromas, especially if the patient's diagnosis of TSC has been missed. Because this patient has an established diagnosis of TSC, it was important to explain to her which treatment options were available for each of her two conditions. She responded moderately well to acne treatments and is considering future treatments for her angiofibromas. The angiofibromas of TSC have been treated most successfully with laser therapy, including the carbon dioxide laser and the pulsed dye laser.11 It is important to convey to the patient that destructive methods, such as laser, dermabrasion, and curettage, are the only treatments that have some success, that the angiofibromas cannot be removed with topical creams, and that they may recur even with use of the destructive methods.

REFERENCES

1. Darling TN, SkamHs MC, Steinberg SM, et al. Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1. Arch Dermalol. 1997; 133(7):853-857.

2. Korf BR. The phakomatoses. CUn Dermalol. 2005;23(l):78-84.

3. Povey S, Hurley MW, Attwood J, et al. Two loci for tuberous sclerosis: one on 9q34 and one on 16pl3. Ann Hum Genet. 1994;58(Pt 2):107-127.

4. Vanderhooft SL, Francis JS, Pagon RA, Smith LT, Sybert VP. Prevalence of hypopigmented macules in a healthy population. J Pediatr. 1996;129(3):355-361.

5. Curatelo P, Cusmai R, Cortesi F, Chiron C, Jambaque I, Dulac O. Neuropsychiatrie aspects of tuberous sclerosis. Ann N YAcadSci. 1991;615:8-16.

6. Jozwiak S, Schwartz RA. Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatrie patients. J Child Neurol. 2000;15(10):652-659.

7. Cook JA, Oliver K, Mueller RF, Sampson J. A cross sectional study of renal involvement in tuberous sclerosis. J Med Genet. 1996;33(6):480484.

8. Brook-Carter PT, Peral B, Ward CJ, et al. Deletion of the TSC2 and PKDl genes associated with severe infantile polycystic kidney disease-a contiguous gene syndrome. Nat Genet. 1994;8(4): 3 28-332.

9. Castro M, Shepherd CW, Gómez MR, lie JT, Ryu JH. Pulmonary tuberous sclerosis. Chest. 1995;107(1):189-195.

10. Rowley SA, O'Callaghan FJ, Osbome JP. Ophthalmic manifestations of tuberous sclerosis: a population based study. Br J Ophthalmol. 2001;85(4):420-423.

11. Papadavid E, Markey A, Bellaney G, Walker NP. Carbon dioxide and pulsed dye laser treatment of angiofibromas in 29 patients with tuberous sclerosis. Br J Dermalol. 2002;147(2):337-342.

10.3928/0090-4481-20060601-08

Sign up to receive

Journal E-contents