ErythromelalgiaNew password for old mystery

2. By Dr: Samir M Al-Minshawy
Lecturer of Neuropediatrics
Minia University

3. Take Home Massage(s)
 Pain may be a gift
 Invest your sympathy
 Trust in yours
 Documentation (Reporting) is A must

4. Case presentation
 History Taking:
 A 3 years-old right-handed boy from Mallawy, Minia presented
with insidious intermittent attacks of bilateral intense pain,
warmth and flushing of feet, each lasting minutes to hours.
 Age of onset was 2 years.
 Symptoms:
 Symmetrical
 Localized to feet and never extended proximally beyond ankles
 Precipitated with exercise and/or warm temperature exposure
 Abated by cooling measures like cold water.

7.  No response to ibuprofen (15mg/kg/dose three times a
day) for 2 to 3 weeks
 A partial response to cetirizine hydrochloride
(2.5mg/kg/once daily).
 Symptoms aggravated when stopped for 1 month as a
test and relieved with restart
 Frequency and severity of attacks were reduced with
exposing to cold air (fan) during an attack
 No history of similar conditions in his family or drug
intake before the precipitation of the attacks.

8. Physical examinations during multiple visits:
 Looks well with no manifestations of acute illness.
 Normal vital signs; no pallor, jaundice or cyanosis
 No organomegaly or lymphadenopathies
 Feet appeared red and warm.

9.  Investigations
 CBC with differential and HB electropheresis
 Serum immunoglobulin E (IgE) titre
 Serum cholesterol and triglycerides
 Serum urea and serum creatinine
 Liver enzymes (alanine aminotransferase and aspartate
aminotransferase
 Serum uric acid
 Urine analysis and stool analysis.
 Fasting and 2 hours post-prandial blood glucose levels.
 X-ray of bones and a Doppler of arteries of both lower limbs
 Nerve conduction velocities of both peroneal nerves
 Bone marrow biopsy
 Pelvic and abdominal sonography
 Brain CT
All were normal.
 Negative antistreptolysin O titre and autoimmune pannel
 Genetic study was expensive

10.  A skin biopsy showing numerous telangiectatic blood vessels
in the capillary dermis associated with sparse perivascular
mononuclear cell infiltrate and some vessels showed swelling
of the endothelial lining. Intimal thickening and thrombi
were lacking.

11.  Written informed consent was obtained from the
child’s father for performing investigations, publication
and for any accompanying images.

15. Pain Syndromes
‫األطفال‬ ‫دموع‬‫أ‬ّ‫د‬‫ش‬‫دموع‬ ‫من‬ ً‫ا‬‫إيالم‬‫الرجال‬
‫مى‬‫زيادة‬

16. Pain Syndromes
 Fibromyalgia
 Complex Regional Pain Syndromes ( Reflex
Sympathetic Dystrophy)
 Erythromelalgia
 Chronic Fatigue Syndrome
 Growing Pains
 Abuse
 Munchausen Syndrome by proxy
 Others

17. Erythromelalgia

18. In 1878, Mitchell (American physician and writer )described and
named ‘erythromelalgia’; redness (erythros) and pain (algos)
involving the extremities (melos).

19.  EM (red neuralgia) is a rare neurovascular peripheral pain
syndrome of which the etiology, pathogenesis, diagnosis and
management are controversial and ambiguous.
 It seems to consist of neuropathological and microvascular
alterations
 The incidence is 2.5 to 3.3 per million per year with male-to-
female ratio of 1:3. Most cases occurring in the fifth and sixth
decades; the majority of cases were not inherited and that
progress of the disease is variable.
 It is a disorder in which blood vessels are episodically
blocked, become hyperemic and inflamed with burning pain
and skin redness. The attacks are triggered by heat, pressure,
mild activity, exertion, insomnia or stress.
 Characterized by episodic erythema, warmth and intense
burning pain, commonly involves the extremities. Ulceration,
peeling of skin over with necrosis and gangrene which can lead
to amputation.

22.  May be primary (idiopathic) or secondary
 May be secondary to serious disorders which should be
excluded in each case (Buttaci CJ: 2006)

23.  The exact pathological mechanism is unknown, several
theories have been proposed especially vasculopathy and/or
neuropathy.
 The neuropathology of primary erythromelalgia arise from
hyperexcitability of C-fibers in the dorsal root ganglion
which results in the severe burning pain with microvascular
alterations in the cutaneous vascular tone. These changes is
due to mutation of the sodium channel NaV1.7.
 Kim et al. reported mutations in the SCN9A gene, which
encodes the Nav1.7 sodium channel, in patients with primary
familial EM.
 Dib-Hajj et al. demonstrated another F1449V mutation in the
Nav1.7 channel

24.  Till now, no confirmatory diagnostic test and the diagnosis is
based on taking a careful history and physical examination during
the episodes.
 Erythromelalgia is a difficult condition to diagnose as there are no
specific tests available. However, reduced capillary density has
been observed microscopically during flaring with reduced
capillary perfusion . Another test that can be done is to have the
patient elevate their legs, and note the reversal(from red to pale)
in skin color. Other tests including quantitative sensory nerve
testing, laser evoked potentials, sweat testing and epidermal
sensory nerve fiber density test(which is an objective test for small
fiber sensory neuropathy
 It can lead to significant long-term morbidity.
 EM in the pediatric population is associated with substantial
morbidity and, sometimes, death.
 No reliable treatment has been established

25. Cook-Norris RH, Tollefson MM, Cruz-Inigo AE, Sandroni P, Davis MD, Davis DM: Pediatric
erythromelalgia: a retrospective review of 32 cases evaluated at Mayo clinic over a 37-year
period. J Am Acad Dermatol 2011, 26:.

26. Neuropathy hypothesis
Association with Astrocytoma
Antiepileptic Medication

27.  Normal CBC with a differential count and bone
marrow examination excluded myeloproliferative
disorders, systemic mastocytosis, other hematological
disorders which may explain the symptomatology of
the child including myelodysplastic syndrome, and
thrombotic and immunologic thrombocytopenic
purpuras. Hemoglobin electrophoresis was done for
the exclusion of chronic hemolytic anemias, especially
sickle cell anemia.

28.  EM may be secondary to connective tissue disorders,
such as rheumatoid arthritis, SLE, Sjِgren’s syndrome
and vasculitis, but the clinical presentation and lab
workup excluded them as autoimmune panel
including CBC and ESR, negative rheumatoid factor,
and antinuclear, anti- Smith and anti-
deoxyribonucleic acid (DNA) antibodies was normal.

29.  There was no X-ray evidence of calcified arteries in
lower limbs. Normal blood pressure, serum cholesterol
and triglycerides levels, blood flow of both lower limbs
through the Doppler which ruled out EM-like
syndromes such as Raynaud’s syndrome and Buerger’s
disease.
 Results of a pelvic and abdominal sonography and
brain CT, which were done to exclude oncologic causes
especially astrocytoma, were normal.

30.  Effective treatment is still unknown as shown
 Avoidance of trigger factors.
 Local measures include cooling or elevating the extremity but ice
can lead to skin necrosis and ulceration.
 Medications such as propranolol, carbamazepine, gabapentin,
tricyclic antidepressants, sodium nitroprusside, calcium channel
blockers and intravenous lidocaine and oral mexiletine had some
symptomatic benefits in a few cases and mainly in adults not in
children.
 Antihistamines are often overlooked, but two cases respod to
cyproheptadine and three cases to pizotifen.
 About 40% of users of sedating antihistamines obtain modest
improvement in their EM, whereas 60% do not obtain
improvement.
 Regarding the non-sedating antihistaminic, cetirizine
hydrochloride, no improvement was observed in previous reports
which is in contradiction to our case in spite of normal serum IgE
titre.

31. Our patient
 The firstand only ( to date) case reported in Egypt
 With the earliest ageof presentation
 Responding to new line of treatment

35. Take Home Massage(s)
 Pain may be a gift
 Invest your sympathy
 Trust in yours
 Documentation (Reporting) is A must

36. ‫أجل‬ ‫من‬ ّ‫رب‬ ‫يا‬ ‫و‬‫الطفولة‬‫وحدها‬‫السلم‬ ‫بركات‬ ‫أفض‬‫شرقا‬‫و‬‫مغرب‬‫ا‬
‫إن‬ ‫و‬ ‫شعب‬ ّ‫ل‬‫ك‬ ‫عن‬ ‫األذى‬ ّ‫د‬‫ر‬ ‫و‬‫يكن‬‫كفورا‬‫و‬‫و‬ ‫أحببه‬‫إن‬‫كان‬‫مذن‬‫با‬
ّ‫رب‬ ‫يا‬ ‫األطفال‬ ‫ضحكة‬ ‫صن‬ ‫و‬‫ها‬ّ‫ن‬‫إ‬‫موحش‬ ‫في‬ ‫دت‬ّ‫غر‬ ‫إذا‬‫الرمل‬‫أعش‬‫با‬
‫السوري‬ ‫للشاعر‬/‫الجبل‬ ‫بدوي‬