isotretinoin is a vitamin a synthetic analogue that has been widely used by dermatologists in the treatment of acne . among the many adverse effects of isotretinoin , eye dryness , corneal and retinal abnormalities , myalgia , true
myopathy , psychiatric problems , and several autoimmune disorders have been described [ 2 , 3 , 4 , 5 , 6 , 7 , 8 ] .
a literature review has revealed very few case reports of autoimmune disorders associated with isotretinoin intake .
isotretinoin - induced inflammatory bowel disease ( ibd ) was the most common of these autoimmune disorders .
some of the patients developed ibd after discontinuation of isotretinoin , while some developed ibd during the intake of isotretinoin .
there is only one report of an association between isotretinoin intake and immune - mediated diabetes mellitus . in this case
, it was concluded that latent autoimmune diabetes mellitus could be clinically revealed after isotretinoin use .
guillain - barr syndrome , which is an autoimmune disease of the nervous system , has been reported in two patients taking oral isotretinoin , and both cases received intravenous immunoglobulin . to the best of our knowledge ,
this is the first reported case of isotretinoin - induced autoimmune thyroiditis and ocular myasthenia gravis ( omg ) resulting from use of isotretinoin .
a 19-year - old caucasian male was referred to our clinic , with a three - week history of diplopia and variable bilateral ptosis ( fig . 1 and fig .
usa ) at 1 mg / kg / day for severe acne disease , for the previous six months .
no use of other medications or occurrence of any stressful events was recorded in his recent history .
he first experienced a sudden onset of right eye ptosis , which recovered spontaneously within two weeks .
one week later , he noted left eye ptosis that was resolved within one week .
two weeks later , the right eye ptosis recurred and was accompanied by sudden onset of diplopia .
the ophthalmic , general medical and family histories for neuromuscular or autoimmune disorders were negative .
physical examination showed moderate periorbital edema and limitations of up- and down - gaze in the left eye .
thyroid function tests revealed free t4 of 3.08 ng / dl ( normal range 0.931.7 ng / dl ) , free t3 of 13.85 pg / ml ( normal range 2.04.4 pg / ml ) and thyroid - stimulating hormone ( tsh ) < 0.005 mu / ml ( normal range 0.274.2 iu / ml ) .
the anti - thyroglobulin antibody level was normal , whereas tsh receptor antibody ( trab ) [ 40 u / l ( normal
< 15 u / l ) ] and anti - thyroid - peroxidase antibody levels were elevated [ 492.2 iu / ml ( normal 034 iu / ml ) ] .
the thyroid ultrasound showed moderately heterogeneous , reduced echogenicity , which was consistent with thyroiditis .
propylthiouracil ( propycil ) , at 200 mg / day , was prescribed by the endocrinologist .
the acetylcholine receptor antibody test , tensilon test , and single fiber electromyography were normal .
computerized tomography of the chest showed no evidence of thymomas . in accordance with the clinical characteristics , oral pyridostigmine ( mestinon , valeant pharmaceuticals , aliso viejo , calif . ,
usa ) at 180 mg / day was initiated . at the second - month follow - up ,
usa ) , at 2.5 units , was injected into the right inferior rectus muscle .
after one month , variable ptosis recurred and diplopia persisted . in order to exclude myopathies
ragged red fibers were seen in the samples , which was consistent with a mitochondrial cytopathy ( mc ) .
pyridostigmine was stopped and oral co - enzyme q10 ( co - enzyme q10 , life time , meridian , idaho , usa ) at 30 mg / day was initiated .
cardiac and neuromuscular disorders may be associated with mc , but were not detected in the patient .
no clinical improvement was seen within one month ; therefore , co - enzyme q10 was discontinued .
oral pyridostigmine at 360 mg / day and oral prednisolone ( deltacortril , pfizer , new york , n.y . , usa ) at 40 mg / day were initiated to treat the concomitant autoimmune thyroiditis and omg .
regarding the patient presented in this case report , there is a possible relationship between isotretinoin intake and concomitant autoimmune thyroiditis and omg .
the clinical symptoms did not reverse upon completion of the acne treatment , since the autoimmune reactions had already been triggered .
it is reported that isotretinoin has immunomodulating effects that may induce some autoimmune diseases such as crohn 's disease , immune - mediated diabetes , and guillain - barr syndrome [ 5 , 6 , 7 , 8 , 9 ] . genetic predisposition and a variety of environmental factors
drugs are one of the important environmental factors , which may be the trigger factor for the development of autoimmune diseases in genetically predisposed people .
it has been shown that isotretinoin is involved in induction of apoptosis , activation of t cells and b cells [ 9 , 11 , 12 ] . in our case , it is unclear how isotretinoin caused the development of autoimmune thyroiditis and omg , but it is possible to suggest that isotretinoin triggered autoimmunity through its immunomodulating effects [ 9 , 11 , 12 ] .
most screening tests for mitochondrial cytopathy are not sensitive , and in this case report , the observed ragged red fibers probably led to a false positive diagnosis . the clinical and laboratory findings and
the response to combined pyridostigmine and steroid treatment were consistent with concomitant autoimmune thyroiditis and omg .
the laboratory and thyroid ultrasound findings and moderate periorbital edema suggested thyroid eye disease ( ted ) .
graves disease was the most likely etiology for the current ted , because tsh receptor antibody was elevated in addition to hormone levels , indicating hyperthyroidism .
periorbital swelling , eyelid retraction , proptosis , and restrictive and congestive ocular myopathy are common signs of ted . in the present case ,
diplopia , due to involvement of extraocular muscles , was a persistent finding and did not resolve until combined high - dose oral pyridostigmine and prednisolone was initiated .
however , normal orbital mri and negative forced duction tests did not support a diagnosis of graves ocular myopathy . however , ptosis , which is not a feature of ted , was one of the presenting signs in the present case . the spontaneous recovery of the ptosis at the second - month follow - up and the following recurrences of the ptosis were most likely due to the fluctuating nature of omg .
however , it has been reported that these tests may be negative in some omg cases . in the current case , the variable ptosis ,
the limitations of eye movements , and response to pyridostigmine were used to determine the diagnosis of omg .
steroids may be effective in both ted and omg , supporting concomitant diagnosis of both diseases .
although oral steroid and pyridostigmine relieved the symptoms , thyroid hormone levels must be checked during the follow - up .
although a clinical diagnosis may be confirmed by laboratory testing , clinical findings of fluctuating and fatigable weakness leading to ptosis and diplopia are the most important elements of diagnosis . in the present case , the emphasis was solely on ted , because of negative test results for omg .
variable ptosis and involvement of the extraocular muscles without any enlarged muscles , as observed by orbital mri , supported the diagnosis of concomitant autoimmune thyroiditis and omg .
patients with acne should be assessed for autoimmune disorders or any predisposition to their development prior to treatment .
clinicians prescribing isotretinoin should be aware of the possible association between isotretinoin intake and concomitant autoimmune thyroiditis and omg .
written informed consent was obtained from the patient for publication of this case report and accompanying images .
a copy of the written consent is available for review by the editor - in - chief of this journal .
 introductionthere are many adverse effects that have been described for isotretinoin . to the best of our knowledge , 
 this is the first report of a possible association of oral isotretinoin intake with autoimmune thyroiditis and ocular myasthenia gravis ( omg).case presentationa 19-year - old caucasian male , who had used oral isotretinoin for severe acne disease for the previous six months , was referred to our clinic . 
 he had a three - week history of diplopia and variable bilateral ptosis . 
 physical examination showed moderate periorbital edema and limitations of up- and down - gaze in the left eye . 
 laboratory findings and thyroid ultrasound were consistent with autoimmune thyroiditis . 
 antithyroid therapy did not relieve the clinical symptoms . 
 concomitant omg was suspected . 
 variable ptosis and a positive response to oral prednisolone of 40 mg / day and pyridostigmine of 360 mg / day supported the diagnosis of concomitant autoimmune thyroiditis and omg.conclusionautoimmune disorders may be triggered by oral isotretinoin treatment . 
 clinicians prescribing isotretinoin should be aware of the possible association between isotretinoin intake and concomitant autoimmune thyroiditis and omg . 
Introduction
Case Presentation
Discussion
Conclusions
Consent
Disclosure Statement