Isotretinoin Failure

This 20-year-old woman has a 6 month history of cystic acne.  Although she has been on isotretinoin for three month her response has been poor and she continues to develop new lesions.  She started on 40 mg of isotretinoin a day but her acne flared and she was dropped to 30 and then 20 mg per day.  Due to her acne flare on isotretinoin, prednisone was started at 40 mg bid (tapered after two weeks).  She is on a combined oral contraceptive but it only has 20 mcg of ethinyl estradiol and spironolactome 100 mg per day.  She was also placed on desloratadine 5 mg a day, but that did not appear to help either. She is feeling discouraged, and sees a therapist for anxiety and that led to a prescription for BuSpar from her therapist.

EXAMINATION:  The examination shows a pleasant, outgoing woman.  She has acne with inflammatory and cystic features on the cheeks and forehead.  Back and chest are clear although she did have some acne on her shoulders that has resolved.  Her weight is 65 kg.  There is no hirsuitism or striae.

Photos 8.5.21(aftr 12 weeks of isotretinoin)

IMPRESSION:  This 20-year-old woman with severe inflammatory cystic continues to have active lesions after 3 months months on isotretinoin.  Her acne worsened significantly after her first month of isotretinoin at 40 mg a day.    

 

Photos Removed for Privacy Issue (for legitimate use please contact djelpernATgmail.com)

PLAN:  For the time being, we will continue prednisone at 20 mg a day for the next week and then drop, isotretinoin 20 mg a day, and continue spironolactone 100 mg a day.  I discussed with her either trimethoprim or Bactrim, but we are going to hold off on that, for the time being.    After a literature review,  an article about adding amoxicillin seemed promising.¹

          Questions:

1. At what point would you initiate a work-up for underlying endocrinopathy, such as Cushings?

2.  Have you treated similar patients who flared with isotretinoin and were difficult to control?

3. Have you had experience with adding amoxicillin in situations like this.

 

Reference:

Safety and effectiveness of amoxicillin in the treatment of inflammatory acne.  Guzman AK, Choi JK, James WD. Int J Womens Dermatol. 2018 Jun 8;4(3):174-175Free Full Text.
Comment from Dr. James:

Amoxicillin is a very good drug for acne. I would start at 500 mg tid, very few get any side effects other than of course possible drug eruption, but most have had penicillin in the past and know if they are allergic or not. At three months I would then go to bid. In the paper it was early in my using it, and I was giving it at lower doses, but I find higher dosing better and well tolerated.

You could also start at a lower dose with isotretinioin, sometimes with prednisone as well for the first three to six weeks, almost always tolerate it in this manner, but hard for those who have flared badly to want to take it again. Avoiding this bad flare is why when I use isotretinoin I start the first month at 20 mg per day, then increase. I have had to start at ten mg per day in some that have flared in the past, along with prednisone.

 

17 year-old girl with 8 year history of scalp dermatitis

The patient is a 17 year-old girl with an 9 year history of thick scales on her scalp.  She has used multiple medications without relief.  The patient has been bullied at school where she has been called “lice girl.”  Socially, this has been traumatic.

O/E:  She is a well-developed and well-nourished 17 yo with thick chestnut colored hair or normal intelligence.  There are no areas of alopecia. Thick, silvery adherent scales are present on the occipital, parietal and temporal scalp.  When these are removed, hair roots come out, too.  The remainder of the cutaneous examination is normal.  No nail dystrophy.

Clinical Images (July 2017)

Lab: Fungal culture negative.  Bacterial culture 3+ Staph aureus.

Failed Treatments (per mother):

"Every single otc dandruff shampoo

Every prescription medicated dandruff shampoo

Scalpicin

Prescribed scalp drops with and without coal tar

Every Tea Tree product you can find otc

Hot oil treatments

P & S Oil

Nutrogena T-gel and T-sal

Olive oil"

Terbinafine 250 mg p.o. x 1 month
Keflex 500 mg b.i.d. x 2 weeks

Scalp Biopsy read by Lynne Goldberg (Boston University Skin Path): was felt to be most compatible with psoriasis.  Seborrhea was in the differential diagnosis but less likely.

Diagnosis:  Working Dx:  Tinea amiantacea secondary to psoriasis.

Discussion: This 17 yo girl has suffered with what appears to be tinea aminatacea for almost a decade.  It appears unlikely that this is psoriasis. Tinea capitis has been ruled out by culture.  Her bacterial culture showed 3+ S. aureus but I suspect this is a secondary invader as she did not improve with cewplanexin.  Since the fungal  culture was negative and these approaches were not helpful, I may recommend isotretinoin.  The use of this has been reported for T. aminatacea only and in a Korean case report.

Dr. Goldberg's rotocol for Scalp Psoriasis, Tinea amiantacea and Related disorders:

1. Wet hair at night

2. Apply Dermasmoothe scalp oil liberally to scalp. Leave on overnight

3. Sleep with this overnight in a shower cap (to protect pillow)

4. Shampoo in the morning with T-Sal or other dandruff shampoo

Do this nightly at first if possible, but after a week or so she will be better and will not need to do it every night.

References:

1. Abdel-Hamid I et al. Pityriasis amiantacea: a clinical and etiopathologic study of 85 patients. Int J Dermatol. 2003 Apr;42(4):260-4.

2. Kwon JI.  Isotretinoin for Tinea amiantacea (A Case Report). Korean J Dermatol 2012;50(11):1002-1005 (In Korean)

3.  Mannino G, McCaughey C, Vanness E. A case of pityriasis amiantacea with rapid response to treatment WMJ. 2014 Jun;113(3):119-20.  Full Free Text.

4. Scalp psoriasis: European consensus on grading and treatment algorithm.  Ortonne J. J Eur Acad Dermatol Venereol. 2009 Dec;23(12):1435-44.

Extensive Darier's Disease

This 55 yo man presents with a flare of Darier’s disease. In his own words, he suffers from “mental illness” and has been on lithium for decades. He very embarassed about his skin and feels that he looks “hideous” because of this. Two yeas ago he had squamous cell carcinoma of the base of the tongue that was treated with surgery, radiation and chemothreapy.  This is in remission presently.

O/E: The examination shows widespread discrete and confluent reddish-brown greasy papules on the the chest and back. 

We have treated him successfully with isotretinoin in the past and were concerned about the possible interaction between lithium and isotretinoin, but the patient is at his wits end with his disease.

PLAN: He was requalified for iPledge today. He will be started on 40 mg of isotretinoin a day. In a month, we will do biochemistry survey, CBC, lipid profile, and lithium level.  We will obtain his last lithium level, in addition.

Have you managed similar patients and if so, what are your recommendations?

The patient was treated with 40 mg of isotretinoin daily.  After a few months, he is completely clear and his dosage is being tapered.

 

References

Isotretinoin treatment of Darier's disease.
J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):721-6.
Dicken CH, et, al.

Isotretinoin: Rare Side-Effects

Isotretinoin (Acutane, RoAcutane, Sotret, Claravis, Amnesteen) is a true wonder drug that has revolutionized the treatment of severe cystinc acne since its introduction in 1980. Over twenty million people have used it. There are some rare idiosyncratic reactions. We welcome comments here from patients, their families and practitioners.

The index case is a is an outgoing 16 yo girl with severe cystic acne with scarring. She was started on isotretinoin 30 mg per day (0.5 mg/kg per day) after routine lab tests were normal. She was on no other medications and had declined oral contraceptives since she is abstinent.

After two weeks, she reported the onset of vivid nightmares. These involved her being in contact with Nazis who were persecuting Christians. (Her step-father is a minister, and she had been studying the Holocaust at school). There is one reference to dreams on isotretinoin, but no reports of nightmares with the drug in the literature. I elected to continue the medication at the same dose and the nightmares resolved.

At week seven of isotretinoin therapy, she started to experience auditory hallucinations. These occurred at school and at home. The voices at home were telling her to kill herself. She developed a mild nosebleed which is a common isotretinoin side-effect the night before an emergency visit to my office, and reported that the voices told her she might as well "finish the job." Scared, she told her parents.

The drug was stopped and the hallucinations disappeared. At her request, she was rechallenged with 10 mg per day. Within a few days, the auditory hallucinations recurred and isotretinoin was discontinued with resolution of symptoms.

Physicians often tend to discount such reports from patients if the reaction is not documented in our medical literature; however patients need to be heard. This case was recently reported.

How many other patients may have had similar symptoms? Is this a coincidence, or a true neuropsychiatric drug-effect?

Have you had an unusual side-effect with isotretinoin? The VGRD Blog may be used as a vehicle to collect singular side-effects to medications, in this case isotretinoin. All responses will be anonymous. We would like to establish a database for idiosyncratic isotretinoin effects that may help other patients and their care givers.

Reference: The Voice of Isotretinoin