Clinicopathologic Manifestations of Fordyce Spots Ann Dermatol Vol. 24, No. 1, 2012 LETTER TO THE EDITOR Clinicopathologic Manifestations of Patients with Ji Hyun Lee, M.D., Ji Hae Lee, M.D., Na Hyun Kwon, M.D., Dong Soo Yu, M.D., Gyong Moon Kim, M.D., Chul Jong Park, M.D., Jeong Deuk Lee, M.D., Si Yong Kim, M.D. Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Clinical summaryClinical Summary
Name: Justine D'Italia
Date of Birth: 01/12/1964
Chief Complaint/Identifying Information:
Ms. D'Italia is a 45-50 year-old woman with frequent falls with stiffening of her body,
easy startling, and gait disturbance since her 20's. She is seeking Best Doctors opinion re
the etiology of her symptoms and recommendations for treatment options.
History of Present Illness:
Ms. D'Italia is a 45-50 year old woman with seropositive rheumatoid arthritis diagnosed
in 2005. She was treated with steroids initially. She is currently on Hydroxychloroquine
and Methotrexate. She was diagnosed with right peroneal tenosynovitis in 2009 and
underwent debridement in November 2010. She has been using a walker since the
surgery. She was found to have left peroneal tendonitis in 2012. She recently started
Isoniazid therapy for latent tuberculosis (equivocal PPD and positive Quantiferon gold
She reports she has multiple family members, including aunts and cousins, with similar
symptoms to the ones she describes below. One aunt has been diagnosed with
hyperekplexia. Evidently some of her family members have been treated with anti-
seizure medications, but these have not been helpful. (Of note, the available neurology
notes do not include this family history.)
Ms. D'Italia reports the following history re her falls and gait disturbance: (There are no
records available until 2006.) She reports in her 20's, she began to fall frequently. There
was no prodrome before falls. She always wore high heels, and she assumed the falls
were due to clumsiness. An MRI (NOS) performed in her 20's was a normal study. She
was treated with Valproic Acid and then Carbamazepine. She continued to fall. At
times, the falls would results in lacerations and concussions. Imaging continued to be
negative. She developed a panic disorder because she never knew when she was about to
fall. She became afraid to walk. She also reports that she became quite sensitive to
environmental stimuli and was easily startled. Whenever she became startled, she would
start to fall. She was admitted to the hospital for 4 days for continuous EEG monitoring.
She was told that she did not have epilepsy, but ant-epileptic drugs were not discontinued
at that time.
She was seen at a different neurology clinic in approximately 2006. 48-hour ambulatory
EEG monitoring was within normal limits. There were four events on the log which had
no EEG correlate. She was started on Lamotrigine to treat a possible seizure disorder at
some point with some benefit for a few years.
In July 2009, Ms. D'Italia fell after tripping over some clutter on the floor. She hit her
head against the arm of a chair and on the tile floor. She did not lose consciousness. She
developed nausea and a severe headache at that time. She presented to 3 ED's over the
next 10 days. Head CT's were negative for a bleed. During the third presentation, she was evaluated by a neurologist, and a lumbar puncture was performed. No fluid was obtained. There was concern for a low pressure headache. She was admitted to the hospital. A blood patch was performed and the headache resolved. An MRI of the brain with and without contrast and an MRA of the head and neck were unremarkable studies. She was evaluated by a neuromuscular disease specialist. A diagnosis of stiff-person syndrome was entertained, but anti-GAD antibodies in late 2009 were negative. The first available office note from a neurologist (the neuromuscular disease specialist) is from May 2010. At the time of the evaluation, Ms. D'Italia reported that she had ataxia. Her falls, which had been quiescent for a long time, had recently resumed. She reported significant life stressors and felt that her nerves were shot. Her falls were described as a feeling of stiffening up and toppling like a tree, which had just been cut down. She was afraid of walking and was using a cane. She was taking Lamotrigine 150 mg bid and Lorazepam 0.5 mg q8hr prn at that time. On exam, the neurologist described that Ms. D'Italia would cry out when he tested her reflexes. Her gait was felt to be unusual. She preferred to hold on to the neurologist or other objects. When walking unassisted, she walked as if she were a toddler who was learning to walk. The lower extremities would elevate from the ground in an exaggerated fashion. Her stance was wide-based and the legs were replaced in a clumsy manner. The neurologist was skeptical that there was a primary neurologic diagnosis. A repeat EEG was ordered. She was referred to a movement disorders specialist. In June 2010, Ms. D'Italia was evaluated by the movement disorders specialist. She described her falls as not preceded by aura and not usually followed by altered consciousness to suggest a post-ictal phase. She would always fall forward. She had sometimes lost consciousness and would sometimes lose control of her urine. Her husband reported that the frequency of falls had increased over the past few months ever since she had been forced to give up an adopted child to its birth mother. On exam, there was a wide based gait with a feeling of insecurity. Ms. D'Italia held on to objects while walking. The impression was of a psychogenic gait disorder. A slow taper of the Lamotrigine was to be recommended as long as a recent EEG was negative. (The EEG was negative for any epileptiform activity.) Physical therapy was recommended. In January of this year, Ms. D'Italia was evaluated by her PCP. She reported that her walking in December was the worst it had ever been. In addition, her anxiety and panic attacks were out of control. She had only been able to work in her office for three days during December. Both Fluoxetine and Sertraline had recently been prescribed and were poorly tolerated. (Citalopram in the past had also been poorly tolerated.) She was taking Lorazepam thee times daily. She was no longer seeing a psychiatrist. She had recently attended 5 hypnotherapy sessions. These seemed to be helping. On exam, she was afraid to walk or stand unaided. With her walker, she was able to walk quickly and without any observed difficulty. She was able to get on and off the exam table unaided without much difficulty. The PCP referred her to neurology and psychiatry. Home physical therapy and occupational therapy were to be considered. Lorazepam was increased from 0.5 mg
tid to 0.5-1 mg tid prn.
Ms. D'Italia returned to the movement disorders specialist. He noted that at her last visit
in 2010, her clinical presentation was consistent with astasia/abasia, commonly
associated with psychogenic gait disorders. She reported that her gait had progressively
worsened over time. She had become dependent on a walker due to frequent falls. The
exam findings did not include any neurologic findings. She was prescribed Amantadine
100 mg bid. A brain MRI was ordered.
Ms. D'Italia recently described symptoms in the following way: She has fallen four
times in the last 6 months. She feels as if her feet "don't walk with her." There are days
when she is asymptomatic, and there are no problems with her gait. There are other days
when her body knows she needs to walk, but she cannot. She is filled with dread at the
thought of leaving her house, and she mainly works from home. She holds on to the
walls in her home to get around.
She has an appointment with a psychiatrist soon. She has recently started physical
therapy. She was recently prescribed Amantadine 200 mg daily by the movement
Ms. D'Italia would like to know if her symptoms have an underlying physiologic cause,
psychological cause, or both.
Past Medical/Surgical History:
Falls and gait disturbance as above
Seropositive rheumatoid arthritis
Vitamin D deficiency
Infertility s/p unsuccessful IVF
Chronic right peroneal tenosynovitis s/p debridement 2010
Left peroneal tendinitis 2012
Excision of perineal cyst 2009
Supracervical hysterectomy and bilateral salpingectomy with ovarian preservation 05/12
Amantadine 200 mg daily
Lorazepam 1.5 mg daily
Hydroxychloroquine 400 mg daily
Methotrexate 20 mg weekly
Folic acid 1 mg daily
Nabumetone 500 mg bid
Isoniazid 200 mg daily
Vitamin B6 50 mg daily
Sulfa drugs: fever, rash, vomiting
Ms. D'Italia is married with one adopted daughter. She is a senior administrative
assistant. She does not smoke. She drinks alcohol occasionally. She does not use illicit
Family history of similar symptoms: one aunt has been diagnosed with hyperekplexia.
She has a first degree cousin who had seizures. He is also an alcoholic.
Her mother died of colon cancer.
Her father died of an MI.
A first cousin and a distant cousin were diagnosed with multiple sclerosis.
Exam by neurologist 05/10:
Exam by movement disorders specialist 06/10:
Exam by PCP 01/13:
07/21/09: MRI of the brain w/wo contrast and MRA of the head and neck:
45-50 year old
12/16/06: 48-hour ambulatory monitoring:
40-45 year old
06/03/10: Awake and drowsy EEG:
Treating Physician's Assessment and Plan:
Ms. D'Italia is a 45-50 year-old woman with seropositive rheumatoid arthritis. She has had
frequent falls with stiffening of her body, easy startling, and gait disturbance since her 20's. She
has injured herself multiple times. Over the years, a diagnosis of epilepsy has been entertained,
and she was treated with various anti-epileptic drugs. Long term EEG monitoring x 2 revealed no
evidence of seizure activity. A diagnosis of stiff man syndrome was entertained. Anti-GAD
antibodies were negative. Lamotrigine was fairly effective for a few years, but episodes became
more frequent during a particularly stressful time in 2010. Over time, she has developed panic
attacks due to the frequent falls. She now avoids going out of the house. Recently, she has been
prescribed Amantadine by her neurologist. She has also started hypnotherapy. She has been
intolerant to selective serotonin uptake inhibitors.
She reports she has multiple family members, including aunts and cousins, with
symptoms similar to hers. One aunt has been diagnosed with hyperekplexia.
1. Please provide a differential diagnosis for Ms. D'Italia's symptom complex.
2. Which of the above diagnoses do you think is the most likely and why?
3. What further testing would you recommend to help confirm a diagnosis and to help
guide treatment planning?
4. In layman's terms, please discuss your leading diagnosis. Explain what it is, the
underlying pathophysiology, the risk factors for development, the demographics, the
diagnostic criteria, the natural history, and associated complications over time.
5. Please outline a specific medical treatment plan including:
(a) the initial dosed for the medications you would recommend; (b) the frequency of administration; (c) a titration schedule, if appropriate; and (d) a plan for introducing new medications over time. 6. Please outline: (1) non-pharmacologic therapeutic modalities; (2) lifestyle modifications; (3) dietary changes/supplements; and (4) alternative therapies that could be helpful in this setting. 7. What are the chances of success for complete resolution of symptoms with the program you have outlined? What percentage of patients will achieve partial success? No change? What percentage of patients will experience even worse symptoms over time? 8. How should Ms. D'Italia be followed over time? Which specialists should be managing her care? 9. If not addressed by the questions above, please provide any further recommendations that you believe will aid in understanding this patient's findings or in guiding future therapeutic decisions. 10. Please provide scientific references that may be helpful to the treating physicians and the patient, and/or that lend support to your recommendations.
Material Safety Data Sheet Status: 06/18/2012 ACRIFIX® CA 0020 1. Chemical Product and Company Identification ACRIFIX® CA 0020 Evonik CYRO LLC 299 Jefferson Road Parsippany, NJ 07054-0677 +1-973-929-8291 Product 24 Hour Emergency Number, CHEMTREC 1-800-424-9300 (TM) indicates trademark