Extracranial and Systemic Causes of Head and Facial Pain










10
A
lthough head or facial pain frequently arises from teeth or
other masticatory structures, it can originate from any of the
tissues or organs in the head and neck or from systemic dis-
eases. In the case of head or facial pain associated with a serious
or life-threatening illness, timely recognition and referral to a physi-
cian are crucial. In cases where the cause of head or facial pain is
not readily apparent, nonmasticatory, extracranial, and systemic pain
sources should be considered in a differential diagnosis. This chapter
briey summarizes these pain sources based on the current clas-
sication format of the International Headache Society (IHS)
1
and
provides lists of associated disorders and symptoms for easy refer-
ence. For further information and treatment guidelines, the reader
Key Points
Clinicians treating orofacial pain patients should inquire
about symptoms in other areas of the body to exclude
systemic diseases as an etiology.
Several systemic conditions may lead to head and facial
pain; therefore, it may be a symptom of a serious underly-
ing disease.
Because pain can be primary or referred, it is necessary
to identify and treat the underlying cause and refer to a
specialist if necessary.
Extracranial and
Systemic Causes
of Head and
Facial Pain

224
10
Extracranial and Systemic Causes of Head and Facial Pain
is referred to other chapters in the text or to
standard medical references.
Pain Stemming from Tissues or
Organs in the Head and Neck
Cranial bones (IHS 11.1)
Most lesions that affect the bones of the skull
are nonpainful.
2
Although it is unusual for pain
to arise from the cranial bones, any pain that
does arise is derived from nociceptors of the
underlying periosteum. Lesions of the skull
most likely to produce headache are those that
are rapidly expansile or aggressively osteoclas-
tic or those that have an inammatory com-
ponent.
3
Included in this group of lesions are
Box 10-1 Head and facial pain arising
from the eyes
Primary pain
Acute glaucoma (IHS 11.3.1)
Convergence disorders (heterophoria
or heterotropia) (IHS 11.3.3)
Ocular inflammation (IHS 11.3.4)
Corneal diseases
Painful ophthalmoplegia
Superior orbital fissure syndrome
Orbital tumors
Metastatic tumors
Orbital schwannomas
Orbital lymphomas
Referred pain
Saccular aneurysms (IHS 6.3.1)
Cavernous sinus inflammation
Carotid-cavernous fistula (IHS 6.3.3)
Carotid artery dissection (IHS 6.5.1)
Myofascial pain
Orbital apex syndrome
Parasellar syndrome
osteomyelitis, multiple myeloma, sickle cell
disease, Paget disease, osteopetrosis, eosino-
philic granuloma, Langerhans cell histiocytosis,
osteoblastoma, immunoglobulin G4–related
disease, non-Hodgkin lymphoma, and meta-
static tumors.
4–10
Eyes (IHS 11.3.x)
Patients with eye pain will most often have
obvious ocular signs accompanying the pain,
making diagnosis relatively easy in such cases.
However, there are occasional instances of
headache or facial pain originating in the eyes
without obvious ocular signs, making diagno-
sis more difcult. Ocular pain may be either
primary or referred (Box 10-1). Primary pain
arises from the ophthalmic division of the
trigeminal nerve, although the maxillary divi-
sion supplies most of the lower eyelid through
its infraorbital branch.
11
The retina and optic
nerve are not capable of nociception, but the
cornea, conjunctiva, iris, extraocular muscles,
dural sheath of the optic nerve, and periorbital
area are supplied with pain-sensing nocicep-
tors. Pain may be perceived as originating in
the orbit by stimulation of the optic nerve at
any point along its path from the face to the
cortex. Possible stimuli include intracranial tu-
mors, tumors of the orbit or paranasal sinuses,
cavernous sinus inammation, and carotid
aneurysms.
12
Facial, cervical, and pericranial
muscles are common sources of pain that may
be referred to the orbit or periorbital areas.
13
Ocular pain associated with inammation is
often accompanied by photophobia and con-
junctival injection. Pain with eye movement
can be due to optic neuritis or anterior sinusitis.
Refractive errors are unlikely to be the cause
of eye pain or headache. Although headache
is often accompanied by ocular or periorbital
pain, in the absence of ocular or periocular nd-
ings, it should be assumed the pain is not due
to a primary ocular disorder, and further test-
ing should be performed.
10
Metastatic tumors
to the orbit may present with diplopia (48%),

225
tumor. Symptoms include TMJ pain, hearing
loss, and otalgia.
24
The prevalence of otologic signs and symp-
toms in adult patients with TMD is high. The
most common otologic symptoms in patients
with TMD are ear fullness, tinnitus, and ear
pain.
25
Tinnitus—particularly pulsatile tinnitus—
reported in patients with TMD caused a mod-
erate impact on quality of life and can be seen
in the presence of background noise, although
daily activities can still be performed.
26
Box 10-2 Head and facial pain arising
from the ears
Primary pain
Otitis media
Otitis externa
Foreign body
Barotrauma
Cholesteatoma (IHS 11.4)
Mastoiditis
Ramsey Hunt syndrome
Herpes simplex
Herpes zoster
Tumors
Referred pain
Temporomandibular disorders
Myofascial pain
Toothache
Auriculotemporal syndrome
Carotid artery dissection (IHS 6.5.1)
Red ear syndrome
Sinuses
Pharyngitis or tonsillitis
Cervical spine arthritis
Pigmented villonodular synovitis
Nodular fasciitis
Foramen of Huschke herniation
Fibroepithelial polyp
Superficial angiomyxoma
Giant cell tumor
Pain Stemming from Tissues or Organs in the Head and Neck
pain (42%), and visual loss (30%) as the most
common symptoms. Breast carcinoma (29%),
melanoma (20%), and prostatic cancer (13%)
are the most common cancers that metasta-
size to the orbit.
14
Orbital infarctions secondary
to sickle cell disease cause acute periorbital
pain, proptosis, ophthalmoplegia, and visual
impairment.
14–16
Orbital schwannomas are be-
nign, well-encapsulated, slowly progressive tu-
mors that may cause symptoms of proptosis,
blurred vision, pain, eyelid swelling, diplopia,
or headache.
17
Orbital lymphomas can present
with proptosis, eyelid lesions, tearing, che-
mosis, decreased visual acuity, ptosis, pain,
squint, and optic nerve compression.
18
Ears (IHS 11.4)
About 50% of earaches are due to structural
lesions of the external or middle ear.
19
The re-
mainder of earaches involve referred pain aris-
ing from disorders such as toothache, temporo-
mandibular disorders (TMDs), pharyngeal or
laryngeal disorders, and cervical disorders.
20,21
Sensory innervations of the ear are supplied
by numerous nerves, including branches of the
5th, 7th, 9th, and 10th cranial nerves, in addi-
tion to branches of the 2nd and 3rd cervical
nerves. Thus, pain originating in the regions
that supply these numerous nerve branches
may be perceived as pain in or around the ears.
Primary painful disorders of the ear can
originate in the auricle, external ear canal,
tympanic membrane, or middle ear (Box
10-2). The common causes of primary otalgia
include otitis media, otitis externa, foreign
body, and barotrauma.
22
Primary otalgia may
also be accompanied by other symptoms in-
cluding vertigo, deafness, or tinnitus.
23
Benign
lesions originating in the temporomandibular
joint (TMJ) have been reported to present as
masses in the external auditory canal. These
lesions include pigmented villonodular syno-
vitis, nodular fasciitis, foramen tympanicum
herniation with salivary stula, broepithelial
polyp, supercial angiomyxoma, and giant cell

226
10
Extracranial and Systemic Causes of Head and Facial Pain
Box 10-3 Head and facial pain arising
from the nose and paranasal sinus
complex
Primary pain
Rhinosinusitis (IHS 11.5)
Acute or chronic sinusitis (IHS 11.5)
Vestibulitis
Septal deviation
Hypertrophic turbinates
Nasal polyposis
Septal abscess/hematoma
Sarcoidosis
Wegener granulomatosis
Tumors
Infections
Referred pain
Toothache
Temporomandibular disorders
Myofascial pain
Migraine
Tension-type headache
Pharyngeal pain
Nose/paranasal sinus complex
The nasal cavity is surrounded by the paranasal
sinuses, which include the maxillary, ethmoid,
frontal, and sphenoid sinuses. Sensory inner-
vation of the nasal/paranasal sinus complex is
supplied by the rst and second divisions of
the trigeminal nerve.
14
Normal function of the
sinuses is dependent upon ciliary action that ac-
tively transports mucous and debris to the ostia
to allow drainage into the middle meatus of the
nasal cavity. If the ostia become blocked due to
inammation or obstruction, uid and bacteria
accumulate, leading to signs and symptoms of
sinusitis. Acute rhinosinusitis is typically sud-
den in onset, lasts up to 4 weeks, and resolves
with antibiotic treatment. Chronic rhinosinusitis
lasts longer than 12 weeks. The symptoms of
acute or chronic rhinosinusitis commonly in-
clude nasal obstruction, nasal congestion, nasal
discharge, nasal purulence, postnasal drip, fa-
cial pressure and pain, alteration in the sense
of smell, cough, fever, halitosis, fatigue, dental
pain, pharyngitis, otalgia, and headache.
27
It is noteworthy that in a study of the symp-
toms of acute sinusitis, maxillary toothache
was highly specic (93%), but only 11% of
patients with sinusitis actually had pain from
the tooth.
28
Headache had a sensitivity of 68%
but only a specicity of 30%. Sinus headache
is a term that is very nonspecic and often
confused with migraine and tension-type
headache because of similarity in location of
the headache. Some studies have shown that
up to 90% of sinus headaches are actually mi-
graines (migraine with sinus symptoms).
29,30
No precise clinical denition exists for what
constitutes a sinus headache, which has al-
ways been a diagnostic dilemma. Contrary to
popular belief, headache is not a typical symp-
tom of rhinosinusitis. Nevertheless, patients
may self-diagnose sinus headache, ignoring
the neurogenic causes of the symptoms and
being unaware that they fulll the diagnos-
tic criteria for chronic migraine. They may
self-treat or receive treatment from primary
care physicians and/or otolaryngologists with
medications for rhinosinusitis, and the chronic
migraine goes undiagnosed.
31
Other sinus-related conditions that are
often considered to induce headache are not
sufciently validated as causes of headache.
These include deviation of nasal septum, hy-
pertrophy of turbinates, atrophy of sinus mem-
branes, and mucosal contact.
1,32
The location
of pain experienced may often provide clues
as to which of the sinuses is primarily involved.
For example, maxillary sinusitis may cause in-
fraorbital or cheek discomfort, ethmoid rhino-
sinusitis may cause tenderness over the lac-
rimal region, frontal sinusitis characteristically
causes pain in the forehead over the orbits,
and pain due to sphenoid sinusitis radiates to
the occiput and vertex areas.
33
Box 10-3 is a
listing of painful disorders of the nose and para-
nasal sinus complex.

You're Reading a Preview

Become a DentistryKey membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here

Was this article helpful?

10Although head or facial pain frequently arises from teeth or other masticatory structures, it can originate from any of the tissues or organs in the head and neck or from systemic dis-eases. In the case of head or facial pain associated with a serious or life-threatening illness, timely recognition and referral to a physi-cian are crucial. In cases where the cause of head or facial pain is not readily apparent, nonmasticatory, extracranial, and systemic pain sources should be considered in a differential diagnosis. This chapter briey summarizes these pain sources based on the current clas-sication format of the International Headache Society (IHS)1 and provides lists of associated disorders and symptoms for easy refer-ence. For further information and treatment guidelines, the reader Key Points◊ Clinicians treating orofacial pain patients should inquire about symptoms in other areas of the body to exclude systemic diseases as an etiology.◊ Several systemic conditions may lead to head and facial pain; therefore, it may be a symptom of a serious underly-ing disease.◊ Because pain can be primary or referred, it is necessary to identify and treat the underlying cause and refer to a specialist if necessary.Extracranial and Systemic Causes of Head and Facial Pain 22410Extracranial and Systemic Causes of Head and Facial Painis referred to other chapters in the text or to standard medical references.Pain Stemming from Tissues or Organs in the Head and NeckCranial bones (IHS 11.1)Most lesions that affect the bones of the skull are nonpainful.2 Although it is unusual for pain to arise from the cranial bones, any pain that does arise is derived from nociceptors of the underlying periosteum. Lesions of the skull most likely to produce headache are those that are rapidly expansile or aggressively osteoclas-tic or those that have an inammatory com-ponent.3 Included in this group of lesions are Box 10-1 Head and facial pain arising from the eyesPrimary pain• Acute glaucoma (IHS 11.3.1)• Convergence disorders (heterophoria or heterotropia) (IHS 11.3.3)• Ocular inflammation (IHS 11.3.4)• Corneal diseases • Painful ophthalmoplegia• Superior orbital fissure syndrome• Orbital tumors• Metastatic tumors• Orbital schwannomas• Orbital lymphomasReferred pain • Saccular aneurysms (IHS 6.3.1)• Cavernous sinus inflammation• Carotid-cavernous fistula (IHS 6.3.3)• Carotid artery dissection (IHS 6.5.1)• Myofascial pain• Orbital apex syndrome • Parasellar syndromeosteomyelitis, multiple myeloma, sickle cell disease, Paget disease, osteopetrosis, eosino-philic granuloma, Langerhans cell histiocytosis, osteoblastoma, immunoglobulin G4–related disease, non-Hodgkin lymphoma, and meta-static tumors.4–10Eyes (IHS 11.3.x)Patients with eye pain will most often have obvious ocular signs accompanying the pain, making diagnosis relatively easy in such cases. However, there are occasional instances of headache or facial pain originating in the eyes without obvious ocular signs, making diagno-sis more difcult. Ocular pain may be either primary or referred (Box 10-1). Primary pain arises from the ophthalmic division of the trigeminal nerve, although the maxillary divi-sion supplies most of the lower eyelid through its infraorbital branch.11 The retina and optic nerve are not capable of nociception, but the cornea, conjunctiva, iris, extraocular muscles, dural sheath of the optic nerve, and periorbital area are supplied with pain-sensing nocicep-tors. Pain may be perceived as originating in the orbit by stimulation of the optic nerve at any point along its path from the face to the cortex. Possible stimuli include intracranial tu-mors, tumors of the orbit or paranasal sinuses, cavernous sinus inammation, and carotid aneurysms.12 Facial, cervical, and pericranial muscles are common sources of pain that may be referred to the orbit or periorbital areas.13Ocular pain associated with inammation is often accompanied by photophobia and con-junctival injection. Pain with eye movement can be due to optic neuritis or anterior sinusitis. Refractive errors are unlikely to be the cause of eye pain or headache. Although headache is often accompanied by ocular or periorbital pain, in the absence of ocular or periocular nd-ings, it should be assumed the pain is not due to a primary ocular disorder, and further test-ing should be performed.10 Metastatic tumors to the orbit may present with diplopia (48%), 225tumor. Symptoms include TMJ pain, hearing loss, and otalgia.24The prevalence of otologic signs and symp-toms in adult patients with TMD is high. The most common otologic symptoms in patients with TMD are ear fullness, tinnitus, and ear pain.25 Tinnitus—particularly pulsatile tinnitus—reported in patients with TMD caused a mod-erate impact on quality of life and can be seen in the presence of background noise, although daily activities can still be performed.26Box 10-2 Head and facial pain arising from the earsPrimary pain• Otitis media• Otitis externa• Foreign body• Barotrauma• Cholesteatoma (IHS 11.4)• Mastoiditis• Ramsey Hunt syndrome • Herpes simplex • Herpes zoster • TumorsReferred pain • Temporomandibular disorders• Myofascial pain• Toothache • Auriculotemporal syndrome• Carotid artery dissection (IHS 6.5.1)• Red ear syndrome• Sinuses • Pharyngitis or tonsillitis• Cervical spine arthritis• Pigmented villonodular synovitis• Nodular fasciitis • Foramen of Huschke herniation• Fibroepithelial polyp • Superficial angiomyxoma • Giant cell tumorPain Stemming from Tissues or Organs in the Head and Neckpain (42%), and visual loss (30%) as the most common symptoms. Breast carcinoma (29%), melanoma (20%), and prostatic cancer (13%) are the most common cancers that metasta-size to the orbit.14 Orbital infarctions secondary to sickle cell disease cause acute periorbital pain, proptosis, ophthalmoplegia, and visual impairment.14–16 Orbital schwannomas are be-nign, well-encapsulated, slowly progressive tu-mors that may cause symptoms of proptosis, blurred vision, pain, eyelid swelling, diplopia, or headache.17 Orbital lymphomas can present with proptosis, eyelid lesions, tearing, che-mosis, decreased visual acuity, ptosis, pain, squint, and optic nerve compression.18Ears (IHS 11.4)About 50% of earaches are due to structural lesions of the external or middle ear.19 The re-mainder of earaches involve referred pain aris-ing from disorders such as toothache, temporo-mandibular disorders (TMDs), pharyngeal or laryngeal disorders, and cervical disorders.20,21 Sensory innervations of the ear are supplied by numerous nerves, including branches of the 5th, 7th, 9th, and 10th cranial nerves, in addi-tion to branches of the 2nd and 3rd cervical nerves. Thus, pain originating in the regions that supply these numerous nerve branches may be perceived as pain in or around the ears.Primary painful disorders of the ear can originate in the auricle, external ear canal, tympanic membrane, or middle ear (Box 10-2). The common causes of primary otalgia include otitis media, otitis externa, foreign body, and barotrauma.22 Primary otalgia may also be accompanied by other symptoms in-cluding vertigo, deafness, or tinnitus.23 Benign lesions originating in the temporomandibular joint (TMJ) have been reported to present as masses in the external auditory canal. These lesions include pigmented villonodular syno-vitis, nodular fasciitis, foramen tympanicum herniation with salivary stula, broepithelial polyp, supercial angiomyxoma, and giant cell 22610Extracranial and Systemic Causes of Head and Facial PainBox 10-3 Head and facial pain arising from the nose and paranasal sinus complex Primary pain • Rhinosinusitis (IHS 11.5)• Acute or chronic sinusitis (IHS 11.5)• Vestibulitis• Septal deviation• Hypertrophic turbinates• Nasal polyposis• Septal abscess/hematoma• Sarcoidosis• Wegener granulomatosis• Tumors• InfectionsReferred pain• Toothache• Temporomandibular disorders• Myofascial pain• Migraine• Tension-type headache• Pharyngeal painNose/paranasal sinus complexThe nasal cavity is surrounded by the paranasal sinuses, which include the maxillary, ethmoid, frontal, and sphenoid sinuses. Sensory inner-vation of the nasal/paranasal sinus complex is supplied by the rst and second divisions of the trigeminal nerve.14 Normal function of the sinuses is dependent upon ciliary action that ac-tively transports mucous and debris to the ostia to allow drainage into the middle meatus of the nasal cavity. If the ostia become blocked due to inammation or obstruction, uid and bacteria accumulate, leading to signs and symptoms of sinusitis. Acute rhinosinusitis is typically sud-den in onset, lasts up to 4 weeks, and resolves with antibiotic treatment. Chronic rhinosinusitis lasts longer than 12 weeks. The symptoms of acute or chronic rhinosinusitis commonly in-clude nasal obstruction, nasal congestion, nasal discharge, nasal purulence, postnasal drip, fa-cial pressure and pain, alteration in the sense of smell, cough, fever, halitosis, fatigue, dental pain, pharyngitis, otalgia, and headache.27It is noteworthy that in a study of the symp-toms of acute sinusitis, maxillary toothache was highly specic (93%), but only 11% of patients with sinusitis actually had pain from the tooth.28 Headache had a sensitivity of 68% but only a specicity of 30%. Sinus headache is a term that is very nonspecic and often confused with migraine and tension-type headache because of similarity in location of the headache. Some studies have shown that up to 90% of sinus headaches are actually mi-graines (migraine with sinus symptoms).29,30 No precise clinical denition exists for what constitutes a sinus headache, which has al-ways been a diagnostic dilemma. Contrary to popular belief, headache is not a typical symp-tom of rhinosinusitis. Nevertheless, patients may self-diagnose sinus headache, ignoring the neurogenic causes of the symptoms and being unaware that they fulll the diagnos-tic criteria for chronic migraine. They may self-treat or receive treatment from primary care physicians and/or otolaryngologists with medications for rhinosinusitis, and the chronic migraine goes undiagnosed.31Other sinus-related conditions that are often considered to induce headache are not sufciently validated as causes of headache. These include deviation of nasal septum, hy-pertrophy of turbinates, atrophy of sinus mem-branes, and mucosal contact.1,32 The location of pain experienced may often provide clues as to which of the sinuses is primarily involved. For example, maxillary sinusitis may cause in-fraorbital or cheek discomfort, ethmoid rhino-sinusitis may cause tenderness over the lac-rimal region, frontal sinusitis characteristically causes pain in the forehead over the orbits, and pain due to sphenoid sinusitis radiates to the occiput and vertex areas.33 Box 10-3 is a listing of painful disorders of the nose and para-nasal sinus complex. 227ThroatThe throat, or pharynx, is divided into the na-sopharynx, oropharynx, and hypopharynx. The sensory supply to the pharyngeal tissues is via branches of the glossopharyngeal and vagus nerves.37 Because of the signicant overlap of innervations to these structures, throat pain is often poorly localized, and pain referral to the ear is common.19 Painful disorders of the throat can be developmental, infectious, inammatory, neuropathic, or neoplastic in origin.38 Box 10-4 contains a list of the most common painful throat disorders.Pain Stemming from Systemic DiseasesOromandibular dystoniaOromandibular dystonia is an uncommon motor disorder that may contribute to oro-facial pain. It is one form of focal dystonia that affects the orofacial region and involves the jaw-opening muscles (lateral pterygoids and anterior digastrics), tongue muscles, facial muscles (especially orbicularis oris and buc-cinator), and platysma. Dystonia is character-ized by an involuntary, repetitive, sustained muscle contraction. The sustained contraction results in an abnormal posturing of a structure and subsequent pain.39,40 Oromandibular dys-tonias are often disabling and affect patients’ overall quality of life with pain, difculty chew-ing food, speech difculty, drooling, and social embarrassment.41Multiple sclerosisMultiple sclerosis (MS) is a systemic inamma-tory autoimmune disease that is characterized by demyelinating lesions and plaques within the central nervous system (CNS). Although the eti-ology and pathogenesis of MS remain unclear, the current literature illustrates that the cause Pain Stemming from Systemic DiseasesSalivary glandsThere are three pairs of major salivary glands: the parotid, submandibular, and sublingual glands. The sensory innervation to the pa-rotid gland is supplied by the auriculotempo-ral branch of the trigeminal nerve, while the secretory bers are derived from the glos-sopharyngeal nerve but transported via the auriculotemporal nerve as well. Both the sub-mandibular and sublingual glands derive their sensory nerve supply from the lingual nerve, while the secretory bers are derived from the chorda tympani.34 Pain originating in the salivary glands is typically inammatory, infec-tious, traumatic, or neoplastic in origin. Com-mon salivary gland disorders that are accompa-nied by pain include sialadenitis, sialolithiasis, epidemic parotitis, and tumors. Diagnosis of salivary gland pain is usually not difcult due to accompanying signs or symptoms.27 For exam-ple, in salivary gland duct blockage or infection, the patient often presents with moderate to severe pain occurring with eating in conjunc-tion with swelling and tenderness of the af-fected gland. Purulent exudate associated with fever and malaise may occur as well. Other clinical signs include a raised earlobe in the case of a parotid swelling, redness of the over-lying skin, lymphadenopathy, and warmth of the overlying skin. Sublingual gland swellings present with a raised oor of the mouth along with obstruction or swelling of the sublingual caruncle.35 First-bite syndrome is diagnosed when patients experience excruciating pain in the ipsilateral parotid gland region at the rst bite of each meal, but this pain improves with subsequent mastication. This is thought to be due to parotid gland sympathetic denervation from surgery with resultant hypersensitivity to parasympathetic impulses. There is no con-sensus on the best treatment for rst-bite syn-drome, although symptoms tend to improve with time.36 22810Extracranial and Systemic Causes of Head and Facial Painof MS is multifactorial and includes genetic pre-disposition together with environmental factors such as exposure to infectious agents, vitamin deciencies, and smoking. These agents are able to trigger a cascade of events in the im-mune system that lead to neuronal cell death accompanied by nerve demyelination and neu-ronal dysfunction.42 The onset of MS symptoms is most often during the third to fourth decade of life, with an average age of onset of 30 years. This is younger than that of trigeminal neuralgia (TN), which has an average age of onset of be-tween 50 and 70 years.43 In patients with MS, TN occurs at approximately 20 times the preva-lence of that in the general population and is usually due to lesions in the intrapontine tri-geminal tract or root-entry zone.44,45 In MS, up to 31% of TN is bilateral, a rate much higher than TN in the non-MS population.31 Treatment of TN pain in MS patients is similar to that in non-MS patients with TN (see chapter 6).Lyme diseaseLyme disease is a multisystem infection caused by the tick-borne spirochete Borrelia burgdorferi. The systemic dissemination of spi-rochetes from the site of the tick bite may re-sult in a characteristic red rash called erythema migrans. The systemic infection primarily in-volves three extracutaneous organ systems: the heart, most commonly causing otherwise unexplained conduction block; the joints, caus-ing arthralgia; and the nervous system, typi-cally much later in infection. Only 10% to 15% of patients develop symptomatic nervous sys-tem involvement, which may present as cranial neuropathy, painful radiculopathy, or lympho-cytic meningitis.46 The most common mani-festation of nervous system infection in both Europe and the United States is cranial nerve involvement—most often facial nerve palsy, which is reported in 5% to 8% of early-stage untreated patients. The disorder itself is indis-tinguishable from Bell palsy in other circum-stances, except that in Lyme disease it can be bilateral in up to 20% to 25% of affected individuals. Although 80% of Lyme-associated cranial nerve palsies affect the facial nerve, other nerves can be involved. Involvement of nerves supplying the extraocular muscles (III, IV, VI) can cause diplopia. Involvement of the fth nerve can cause hypoesthesia or pain and headaches; seventh nerve involvement can re-sult in hearing changes or vertigo.47,48Box 10-4 Head and facial pain arising from the throatPrimary pain • Laryngopharyngeal reflux• Allergic rhinitis with postnasal drip• Chronic mouth breathing• Foreign body• Muscle tension dysphonia• Vocal cord granuloma• Mucositis• Granulomatous diseases (rheumatoid arthritis, gout)• Pemphigus• Kawasaki disease• Glossopharyngeal neuralgia• Tumors• Viral pharyngitis• Influenza• Mononucleosis• Nonstreptococcal bacterial pharyngotonsillitis• Streptococcal pharyngitis• Peritonsillar abscess• Tonsillitis• Candidiasis• Deep space neck infection (retropharyngeal/parapharyngeal space infection)• Epiglottitis/supraglottitisReferred pain• Temporomandibular disorders• Myofascial pain• Gastroesophageal reflux disease • Cardiac pain 229BruxismA recent international consensus position paper dened bruxism as a repetitive jaw-muscle activity characterized by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. Bruxism has two distinct circa-dian manifestations: it can occur during sleep (sleep bruxism) or during wakefulness (awake bruxism).49 Awake bruxism is characterized by tooth clenching during waking hours. Although awake bruxism is a distinctive entity to sleep bruxism, there appears to be considerable overlap in some individuals.50 Based on the limited scientic evidence, it appears that the pathophysiology of awake bruxism may be re-lated to the limbic portion of the basal ganglia.51 It may be viewed as a response to stress or anxiety and affects 20% of the population.35,52The prevalence of sleep bruxism is es-timated by subjective grinding noises dur-ing sleep and is reported to be 5% to 8% in adults, 10% to 20% in children, and 3% in the elderly.53–56 Risk factors for sleep brux-ism include smoking, caffeine intake, use of illicit drugs, sleep-disordered breathing, and anxiety.57–62 Patients with sleep bruxism may present with numerous clinical features based on self-report, partner report, and clini-cal observations (Box 10-5). Most sleep brux-ism episodes (82%) occur in non–rapid eye movement sleep, predominantly in stages 1 and 2 of sleep.64 Studies looking at the physi-ologic events involving sleep bruxism reveal a cascade of events involving autonomic sympathetic cardiac activation leading to mi-croarousal prior to sleep bruxism episodes. This cascade of events includes temporary in-creases in sympathetic tone, heart rate, α and δ electroencephalogram (EEG) activity, infrahy-oid muscle activity, and respiratory activity.51–54Connective tissue diseasesConnective tissue diseases are the result of systemic autoimmune dysfunction and dys-regulation involving one or multiple organs.65 This section discusses more common connec-Box 10-5 Clinical features of sleep bruxism*Self-report from patient or sleep partnerSleep• Sleep partner complains of grinding noise (occasionally tapping noise with oromandibular myoclonus)Waking in the morning• Patient reports jaw muscle discomfort or fatigue• Temporal headache of short duration• Difficulty in jaw opening, jaw stiffness, temporomandibular joint noise• Tooth hypersensitivity to cold stimuli (eg, food, beverage, or air)Clinical observationsVisual inspection• Tooth wear, fracture, and cervical defects• Tongue indentationDigital palpation• Masseter muscle hypertrophy during voluntary clenching (bilateral)• Jaw muscle tenderness (masseter, temporalis) and temporomandibular joint painMiscellaneous• Dental restoration failure or fracture (eg, crown, denture, inlay, implant)• Occlusal trauma• Tongue biting (observed in oromandibular myoclonus)*Adapted with permission from Kato and Lavigne.63Pain Stemming from Systemic Diseases 23010Extracranial and Systemic Causes of Head and Facial Paintive tissue diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, and systemic sclerosis. Other less common connective tissue diseases such as dermatomyositis, polymyositis, and mixed connective tissue diseases may also contrib-ute to orofacial pain and dysfunction.65Systemic lupus erythematosusSystemic lupus erythematosus is a multiorgan connective tissue disease related to abnormal production of autoantibodies, multisystem in-ammation, and vasculopathy. The Systemic Lupus Collaborating Clinics’ classication for diagnosis of systemic lupus erythematosus consists of 17 criteria, of which at least 4 must be met, including at least 1 clinical criterion and 1 immunologic criterion. Clinical criteria include but are not limited to the presence of a rash, oral ulcers, or synovitis (in at least two joints), and immunologic criteria include but are not limited to elevated antinuclear an-tibodies (ANAs), lupus anticoagulant, or low complement. Alternatively, biopsy-proven lupus nephritis in the presence of ANAs or anti-double-stranded DNA (anti-dsDNA) antibodies may be used.66 TMJ pain, locking, and crepitation have been reported in sys-temic lupus erythematosus patients. Similarly, trigeminal neuropathy has been reported to develop as an initial presentation or gradually with this disease.65Rheumatoid arthritisRheumatoid arthritis is a chronic, systemic in-ammatory disease in which proinammatory cytokines destroy articular cartilage and sub-chondral bone.65 The diagnosis of rheumatoid arthritis is based on the American College of Rheumatology/European League Against Rheu-matism classication criteria, and there are updated guidelines for its treatment.67 Half of rheumatoid arthritis patients have TMJ pain and swelling, jaw stiffness, and limited mouth open-ing.68 However, involvement of the TMJ typi-cally occurs later in this disease process than other joints, so TMJ pain as the initial presenta-tion of rheumatoid arthritis is rare.69 Fibrous and bony ankylosis may occur with disease progres-sion.70 Imaging of the TMJ with computed to-mography (CT) or magnetic resonance imaging (MRI) scans may reveal joint effusion, synovial proliferation, marrow edema, altered disc mor-phology and displacement, and condylar abnor-malities, namely erosions, attening, sclerosis, subchondral cysts, and osteophytes.71,72 Class II malocclusion involving heavy posterior contacts and anterior open bite occur in advanced cases of condylar destruction.73Sjögren syndromeSjögren syndrome is characterized by chronic inammation of exocrine glands, principally affecting the lacrimal and salivary glands. The decrease in exocrine secretions is caused by autoreactive lymphocytic inltrates replac-ing epithelium, causing keratoconjunctivitis sicca and hyposalivation.65 The diagnosis of primary Sjögren syndrome is based on the 2016 American College of Rheumatology/European League Against Rheumatism clas-sication criteria based on the weighted sum of ve items: anti-Sjögren-syndrome-related antigen A antibody positivity and focal lym-phocytic sialadenitis with a focus score of ≥ 1 foci/4 mm4, each scoring 3; an abnormal ocular staining score of ≥ 5 (or van Bijsterveld score of ≥ 4); a Schirmer test result of ≤ 5 mm/5 min; and an unstimulated salivary ow rate of ≤ 0.1 mL/min, each scoring 1. Patients who have a total score of ≥ 4 along with signs and symptoms of Sjögren syndrome would fulll the criteria.74Peripheral neuropathy including trigeminal neuropathy characterized by facial numbness and paresthesia has been reported.75,76 Signs of TMDs such as jaw joint sounds, tender-ness of the masticatory muscles, and limited range of jaw movement were more common in Sjögren syndrome.77 Similarly, the preva-lence of headache was 78.1% among Sjögren syndrome patients, with migraine (54%) and 231tension-type headache (24.1%) being the most common types.78Systemic sclerosisSystemic sclerosis is characterized by ab-normal brosis and subsequent damage and dysfunction of the skin, vasculature, and inter-nal organs.65 Microstomia secondary to lim-ited mouth opening from brosis is a known orofacial manifestation.79–81 The diagnosis of systemic sclerosis is based on the joint 2013 classication criteria of the American College of Rheumatology and the European League Against Rheumatism. Essentially, the diagno-sis of systemic sclerosis may be established based on skin thickening of the ngers extend-ing proximal to the metacarpophalangeal joints. Alternatively, seven additive items of varying weights may apply, including skin thickening of the ngers, ngertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud phenomenon, and disease-related autoantibodies.82 TMJ pain and swelling sec-ondary to synovitis have been noted among systemic sclerosis patients.83 Patients with systemic sclerosis often complain of muscle pain with chewing, headache, and difculty with mouth opening.84 Erosion of the coronoid process, condyle, angle of the mandible, and ramus may also be noted on radiographs.63,85,86 Trigeminal neuropathy involving pain and sen-sory loss has been reported, as have symp-toms consistent with trigeminal neuralgia.87,88 There are also reports of giant cell arteritis (GCA) in patients with systemic sclerosis.89FibromyalgiaFibromyalgia is a pain disorder likely neuro-genic in origin presenting as chronic wide-spread allodynia and/or hyperalgesia. It is postulated that bromyalgia may in fact be a misnomer as it merely represents the severe end of the chronic widespread pain spectrum. There is also debate on whether individuals diagnosed with bromyalgia or chronic wide-spread pain need to be classied as such, as both conditions are treated similarly.90 Although its pathophysiology remains an enigma, it is purportedly related to peripheral nerve damage as a result of oxidative stress and mitochondrial dysfunction and inamma-tion.91 Also, abnormal processing of the pe-ripheral stimuli within the CNS is thought to be involved.92 Its common symptoms include pain for at least 3 months involving the right and left side of the body, above and below the waist, and in the axial skeleton, associated with fatigue and sleep disturbances.93 Other related symptoms include tenderness, stiff-ness, anxiety, depression, and cognitive ob-scurity. The most common comorbidities for bromyalgia are mood and anxiety disorders. Other comorbid conditions include irritable bowel syndrome, tension-type headache, migraine, interstitial cystitis, prostadynia, vul-vodynia, chronic pelvic pain, and TMDs.94 Cur-rent clinical diagnostic criteria for bromyalgia from the American College of Rheumatology exclude counting tender points as previously required.95There have been numerous studies sug-gesting a relationship between TMDs and -bromyalgia. Up to 75% of bromyalgia patients present with signs and symptoms consistent with TMDs.96 One study showed that 53% of bromyalgia patients reported face pain, of which 71% fullled the Research Diagnostic Criteria for TMDs.97 Practitioners treating orofa-cial pain patients should inquire about pains in other areas of the body to exclude bromyalgia as an etiology.Lymphatic systemThe lymphatic system is composed of an ex-tensive network of small lymphatic capillaries, larger lymphatic vessels, and lymph nodes. The lymphatic system functions as a supple-mentary drainage system that collects intersti-tial uid, protein, and cells and returns them to Pain Stemming from Systemic Diseases 23210Extracranial and Systemic Causes of Head and Facial Paincirculation. In the head and neck, lymph nodes are grouped into chains, located both within subcutaneous tissues and in deeper tissues associated with muscle and fascial planes. The lymph chains include the occipital, preauricu-lar, postauricular, parotid, buccal, mandibular, submandibular, submental, supercial cervical, internal jugular, spinal accessory, and supracla-vicular lymph nodes.In health, lymph nodes generally are not palpable. Lymphadenopathy, which is an al-teration in lymph node size, number, and con-sistency, may indicate pathology, possibly due to a drug reaction, infection, immunologic dis-order, or malignancy.98,99 Infective causes may be local or systemic and include bacterial, fun-gal, and viral disease. Inammatory lymphade-nopathy may also be of a noninfective nature from disorders such as sarcoidosis or connec-tive tissue disease. Neoplastic enlargement can be due to primary lymph node disease or metastatic disease.In the head and neck, the most common node to be enlarged is the jugulodigastric node, secondary to a viral upper respiratory tract infection.76 This node is located just infe-rior and anterior to the angle of the mandible. Solitary enlarged nodes are generally due to a local or regional problem, while multiple enlarged nodes suggest systemic disease. Enlarged nodes that are soft, freely movable, and tender are likely inammatory. Nodes that are greater than 1 cm, rm or rubbery, xed to underlying tissue, or matted together and nontender are likely neoplastic. If a cervical lymph node is noted to be greater than 2 cm, the potential for malignancy increases signi-cantly. This risk increases substantially if the cervical lymph node is greater than 3 cm in diameter.100 The differential diagnoses of non-painful lymphadenopathies include Hodgkin lymphoma, non-Hodgkin lymphoma, leuke-mia, and plasmacytoma. Most pain disorders associated with the lymphatic system occur secondary to a regional acute inammatory process (Box 10-6).Blood vesselsVascular disease may be a source of head and facial pain (Box 10-7). Orofacial pain is a com-mon presenting symptom of GCA (also known as temporal arteritis), a condition caused by granulomatous inammation of the temporal artery or other branches of the aortic arch. It is found predominantly in people over the age of 50 years, often in the seventh and eighth de-cade of life. There appears to be an association between GCA and polymyalgia rheumatica, an inammatory rheumatic condition that affects individuals over age 50 years. Temporal artery biopsies of polymyalgia rheumatica patients without clinical characteristics of GCA showed expression of cytokines (inammation) with-out overt vasculitis.101 GCA is characterized by a swollen, tender supercial temporal artery, headache, hip and shoulder girdle pain, and constitutional symptoms.102 A prominent fea-ture of the disease is jaw claudication charac-terized as an aching cramp in the masseter or temporalis muscles produced by jaw function. Another feature of the disease is an erythro-cyte sedimentation rate of at least 40 mm/h as well as an elevated C-reactive protein level; the C-reactive protein level is a more sensitive marker than the erythrocyte sedimentation rate.103 The combination of elevated erythro-cyte sedimentation rate and C-reactive protein resulted in improved specicity compared with either test alone; however, neither test is su-perior to the temporal artery biopsy to estab-lish the diagnosis.104 The most serious aspect of this disease is blindness that can occur due to inammation of the posterior ciliary arteries with anterior ischemic optic neuropathy; there-fore, immediate referral to the hospital is nec-essary.78 This disorder can easily be confused with TMDs, and prompt, denitive diagnosis via a long-segment temporal artery biopsy is necessary.105 Treatment involves prednisolone, 60 to 80 mg daily for 4 to 6 weeks and then gradually tapered as symptoms improve over 12 to 24 months.106 233Box 10-6 Etiology of head and neck lymphadenopathy*I. Infectious diseases• Viral: Infectious mononucleosis (Epstein-Barr virus, cytomegalovirus), infectious hepatitis, herpes simplex, human herpes virus 6, varicella zoster virus, rubella, measles, adenovirus, human immunodeficiency virus• Bacterial: Streptococcus, staphylococcus, cat-scratch disease, brucellosis, tularemia, chancroid, tuberculosis, atypical mycobacterial infection, primary and secondary syphilis, diphtheria, leprosy• Fungal: Histoplasmosis, coccidioidomycosis, paracoccidioidomycosis• Chlamydial: Lymphogranuloma venereum, trachoma• Parasitic: Toxoplasmosis, leishmaniasis, trypanosomiasis, filariasis• Rickettsial: Scrub typhus, rickettsialpoxII. Immunologic diseases• Rheumatoid arthritis• Mixed connective tissue disease• Systemic lupus erythematosus• Dermatomyositis• Sjögren syndrome• Serum sickness• Drug hypersensitivity• Primary biliary cirrhosis• Graft-vs-host disease• Silicone-associated• Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA)III. Malignant diseases• Hematologic (Hodgkin or non-Hodgkin lymphoma, acute lymphoblastic leukemia, chronic lymphoblastic leukemia, hairy cell leukemia, malignant histiocytosis, T-cell lymphoma, multiple myeloma with amyloidosis)• Metastatic from primary sitesIV. Lipid storage disease• Gaucher• Niemann-Pick• TangierV. Endocrine disease• Hyperthyroid• Adrenal insufficiency• ThyroiditisVI. Other disorders• Castleman disease (giant lymph node hyperplasia)• Sarcoidosis• Dermatopathic lymphadenitis• Lymphomatoid granulomatosis• Kikuchi disease (histiocytic necrotizing lymphadenitis)• Kawasaki disease (mucocutaneous lymph node syndrome)• Histiocytosis X• Severe hypertriglyceridemia*Adapted with permission from Parisi and Glick.99Box 10-7 Head and facial pain arising from blood vesselsPrimary pain • Subarachnoid hemorrhage (IHS 6.2.2)• Unruptured vascular malformation (IHS 6.3)• Saccular aneurysm (IHS 6.3.1)• Arteriovenous malformation (IHS 6.3.2)• Giant cell arteritis (IHS 6.4.1)• Primary intracranial angiitis (IHS 6.4.2)• Systemic lupus erythematosus (IHS 6.4.3)• Carotid or vertebral artery dissection (IHS 6.5.1)• Postcarotid endarterectomy (IHS 6.5.2)• Cerebral venous thrombosis (IHS 6.6)• Arterial hypertension (IHS 10.3)Pain Stemming from Systemic Diseases 23410Extracranial and Systemic Causes of Head and Facial PainVertebral artery syndrome (ICD-10 G45.0)Vertebral artery (VA) involvement can contrib-ute to various cervicogenic headaches. Syn-dromes with similar symptoms include VA compression syndrome (ICD-10 M47.12), ver-tebral basilar syndrome (ICD-10 G45.0), and benign paroxysmal positional vertigo (ICD-10 H81.13). The major extracranial region of the vertebral artery is protected by the vertebral canal and the surrounding soft tissue struc-tures; however, there is vulnerability from the second cervical vertebrae to the foramen magnum. Vertebral artery injury in the suboc-cipital region can occur from severe cervical spine trauma, such as a fracture of the atlas, whereas compression may exist in the pres-ence of Barré-Liéou syndrome.107 Red ags immediately necessitate further testing to rule out vertebral artery involvement; these in-clude disorientation, nausea, vomiting, visual disturbances, dizziness, or vertigo that occur simply by changing from a non-weight-bearing (supine) position to a weight-bearing position (ie, sitting or standing).73,108–111 An experienced physician or physical therapist should perform the assessment, which can be curtailed in favor of neurologic and radiologic testing if any of the above red ags reoccur or intensify during the evaluative process. Active cervical spine range of movement and provocation testing into positions of rotation, side-bending, and extension can be used to stretch, narrow, or kink the ipsilateral and/or contralateral VA; however, this must be performed with great caution, and the reliability is questionable un-less performed by an experienced clinician.73–76 The delineation between labyrinthine and VA involvement should also be considered. The trained dentist can auscultate the carotid and subclavian arteries for bruits with the patient in a seated position and the head in neutral, but further testing in positions of cervical rotation and extension to each side should be desig-nated to others.73Barré-Liéou Syndrome (ICD-10 M53.0)Irritation of the vertebral artery or posterior cervical sympathetic network via stretch-ing or compression forces can give rise to Barré-Liéou syndrome, which is also known as posterior cervical sympathetic syndrome.77 This rare syndrome, characterized by intracra-nial vasoconstriction, may cause widespread facial and cranial symptomatology that can mimic migraine, tension-type headache, si-nusitis, and craniofacial dysautonomia, given the involvement of the trigeminal spinal tract, upper cervical roots, posterior sympathetic -bers, and vertebral artery. Head and neck pain that falls into the Barré-Liéou category is usu-ally continuous but variable with qualitative characteristics that consist of throbbing, burn-ing, stinging, or pinching sensation.77,112,113 Tin-nitus, decreased auditory perception, a feel-ing of dust in the eye, blurred vision, tearing, nasal irritation, and hoarseness may also exist. One or more of these symptoms, in addition to pain, may become evident or exacerbated by active range of movement or positional or manual suboccipital testing techniques, pri-marily indicative of vertebral artery testing. It is imperative that any positive ndings be further evaluated by a denitive neurologic examination. This syndrome is very controver-sial as it may simply fall into the category of a vertebral artery syndrome associated with other compressive forces within the suboc-cipital fossa.79Other systemic causes of head and facial painThere are many systemic diseases and dis-orders that are accompanied by headache or facial pain. Included among these are meta-bolic and endocrine disorders, infectious dis-ease, autoimmune disease, cardiovascular dis-ease, renal disease, and pulmonary disease. Box 10-8 lists some of the more common 235of these systemic diseases. It is beyond the scope of this chapter to discuss these many entities; however, the practitioner should re-main alert to include systemic disease in a dif-ferential diagnosis when facial pain is accom-panied by systemic signs or symptoms.47,114 Symptoms that may suggest systemic disease are listed in Box 10-9.115,116 In these instances, head or facial pain is merely an accompanying symptom of a potentially serious underlying disease, and the clinician must guard against the trap of attempting to treat the facial pain when a much more serious underlying prob-lem is present.117, 118 In these situations, refer-ral to the appropriate health clinician must be considered. In addition to these disorders, the reader is referred to chapter 4 for a discussion of other worrisome constitutional symptoms.References1. Headache Classication Committee of the International Headache Society. The international classication of headache disorders, 3rd edition (beta version). Cepha-lalgia 2013; 33:629–808.2. Weiss HD, Stern BJ, Goldberg J. Post-traumatic mi-graine: Chronic migraine precipitated by minor head or neck trauma. Headache 1991; 31:451–456.3. Göbel H, Edmeads JG. Disorders of the skull and cervi-cal spine. In: Olesen J, Goadsby PJ, Ramadan NM, Tfelt-Hansen P, Welch KMA (eds). The Headaches, ed 3. Philadelphia: Lippincott Williams & Wilkins, 2006: 1003–1011.4. Arends S, Coebergh JA, Kerkhoffs JL, van Gils A, Koppen H. Severe unilateral headache caused by skull bone infarction with epidural haematoma in a patient with sickle cell disease. Cephalalgia 2011; 31: 1325–1328.5. Dlouhy BJ, Menezes AH. Osteopetrosis with Chiari I malformation: Presentation and surgical management. J Neurosurg Pediatr 2011; 7:369–374.6. Loh JK, Su YF, Hwang SL, Chai CY, Howng SL, Lieu AS. Eosinophilic granuloma of the occipital bone in an adult: A case report. Kaohsiung J Med Sci 2011; 27:76–79.7. Muzumdar D, Balasubramaniam S, Jhawar S, Goel A. Massive benign osteoblastoma of the suboccipital bone and foramen magnum region. Pediatr Neurosurg 2010; 46:232–237.8. Soni CR, Kumar G, Sahota P, Miller DC, Litofsky NS. Metastases to Meckel’s cave: Report of two cases and comparative analysis of malignant tumors with menin-gioma and schwannoma of Meckel’s cave. Clin Neurol Neurosurg 2010; 112:927–932.Box 10-8 Head and facial pain arising from systemic disease• Anemia• Adrenal insufficiency• Arthritides – Rheumatoid arthritis – Osteoarthritis – Psoriatic arthritis – Systemic lupus erythematosus• Chronic pulmonary failure with hypercapnia• Diabetes mellitus • Fibromyalgia • Hashimoto thyroiditis• Herpes zoster• HIV/AIDS• Hypertension/pheochromocytoma• Infectious mononucleosis• Ischemic heart disease• Lyme disease• Menopause• Menstruation• Metastatic malignancies• Multiple sclerosis• Primary malignancies• Renal failure (uremia)/dialysisBox 10-9 Signs or symptoms suggestive of systemic disease• Chest pain• Chronic fatigue• Extreme hunger or thirst• Fever• Generalized aches and pains• Malaise• Palpitations• Shortness of breath• Skin lesions• Tachycardia• Unintentional weight loss or gainReferences 2361023610Extracranial and Systemic Causes of Head and Facial Pain9. Singh AD, Soneja M, Memon SS, Vyas S. Interesting case of base of skull mass inltrating cavernous si-nuses. BMJ Case Rep 2016; 2016:217669.10. Bhatoe HS, Ambastha R. Primary non-Hodgkin’s lym-phoma of the cranial vault in a child. J Neurooncol 2016; 126:209–211.11. Beck RW, Smith CH. Trigeminal nerve. In: Duane TD, Jaeger EA (eds). Biomedical Foundations in Ophthal-mology. Philadelphia: Harper & Row, 1983; 1–16.12. Orcutt JC. Ocular and periocular pain. In: Loeser JD (ed). Bonica’s Management of Pain. Philadelphia: Lip-pincott Williams & Wilkins, 2001:925–935.13. Jaeger B. Overview of head and neck region. In: Simons DG, Travell JG, Simons LS (eds). Travell & Simons’ Myo-fascial Pain and Dysfunction: The Trigger Point Manual. Baltimore: Williams & Wilkins, 1999:237–277.14. Valenzuela AA, Archibald CW, Fleming B, et al. Orbital metastasis: Clinical features, management and out-come. Orbit 2009; 28:153–159.15. Ganesh A, Al-Zuhaibi S, Pathare A, et al. Orbital infarc-tion in sickle cell disease. Am J Ophthalmol 2008; 146:595–601.16. Peleg A, Heran MK, White VA, Chang WY, Rootman J. Malignant lymphoproliferative disorders extending into the orbit from the paranasal sinuses. Orbit 2009; 28: 80–87.17. Pointdujour-Lim R, Lally SE, Shields JA, Eagle RC, Shields CL. Orbital schwannoma: Radiographic and his-topathologic correlation in 15 cases [epub ahead of print 28 March 2017]. Ophthal Plast Reconstr Surg doi: 10.1097/IOP.0000000000000900.18. Briscoe D, Saeh C, Ton Y, Shapiro H, Assia EI, Kidron D. Characteristics of orbital lymphoma: A clinicopatho-logical study of 26 cases [epub ahead of print 31 March 2017]. Int Ophthalmol doi: 10.1007/s10792-017-0457-y.19. Göbel H, Baloh RW. Disorders of ear, nose, and sinus. In: Olesen J, Goadsby PJ, Ramadan NM, Tfelt-Hansen P, Welch KMA (eds). The Headaches, ed 3. Philadelphia: Lippincott Williams & Wilkins, 2006:1019–1027.20. Simons DG, Travell JG, Simons LS (eds). Travell & Simons’ Myofascial Pain and Dysfunction: The Trigger Point Manual. Baltimore: Williams & Wilkins, 1999.21. Wright EF. Referred craniofacial pain patterns in patients with temporomandibular disorder. J Am Dent Assoc 2000; 131:1307–1315.22. Ely JW, Hansen MR, Clark EC. Diagnosis of ear pain. Am Fam Physician 2008; 77:621–628.23. Dray TG, Weymuller EA. Pain in the ear, midface, and aerodigestive tract. In: Loeser JD (ed). Bonica’s Man-agement of Pain. Philadelphia: Lippincott Williams & Wilkins, 2001:936–947.24. Williams RA, Jackler RK, Corrales CE. Benign temporo-mandibular joint lesions presenting as masses in the external auditory canal. Otol Neurotol 2017; 38: 563–571.25. Porto De Toledo I, Stefani FM, et al. Prevalence of oto-logic signs and symptoms in adult patients with tem-poromandibular disorders: A systematic review and meta-analysis. Clin Oral Investig 2017;21:597–605.26. Lacerda AB, Facco C, Zeigelboim BS, Cristoff K, Stechman JN, Fonseca VR. The impact of tinnitus on the quality of life in patients with temporomandibular dysfunction. Int Tinnitus J 2016; 20:24–30.27. Lanza DC, Kennedy DW. Adult rhinosinusitis dened. Otolaryngol Head Neck Surg 1997; 117:S1–S7.28. Williams JW, Simel DL, Roberts L, Samsa GP. Clinical evaluation for sinusitis. Making the diagnosis by history and physical examination. Ann Intern Med 1992; 117: 705–710.29. Schreiber CP, Hutchinson S, Webster CJ, Ames M, Richardson MS, Powers C. Prevalence of migraine among patients with history of self-reported or physician-diagnosed “sinus” headache. Arch Inten Med 2004;164:1769–1772.30. Eross E, Dodick D, Eross MD. The sinus, allergy and migraine study (SAMS). Headache 2007;47:213–224.31. Gryglas A. Allergic rhinitis and chronic daily headaches: Is there a link? Curr Neurol Neurosci Rep 2016; 16(4):33.32. Cady RK, Schreiber CP. Sinus problems as a cause of headache refractoriness and migraine chronication. Curr Pain Headache Rep 2009; 13:319–325.33. Hadley JA, Schafer SD. Clinical evaluation of rhinosinus-itis: History and physical examination. Otolaryngol Head Neck Surgery 1997; 117:S8–S11.34. Bradley PJ. Tumors of the salivary gland. In: Jones AS, Phillips DE, Hilgers FJ (eds). Diseases of the head and neck, nose and throat. London: Arnold, 1998:329–346.35. Ram S, Kumar SK, Clark GT. Using oral medications, infusions and injections for differential diagnosis of oro-facial pain. J Calif Dent Assoc 2006; 34:645–654.36. Wong EH, Farrier JN, Cooper DG. First-bite syndrome complicating carotid endarterectomy: A case report and literature review. Vasc Endovascular Surg 2011; 45: 459–461.37. Sharp J, Watkinson JC. Surgical anatomy of the head and neck. In: Jones AS, Phillips DE, Hilgers FJ (eds). Diseases of the head and neck, nose and throat. Lon-don: Arnold, 1998:11–23.38. Chan TV. The patient with sore throat. Med Clin North Am 2010; 94:923–943.39. Clark GT, Ram S. Four oral motor disorders: Bruxism, dystonia, dyskinesia and drug-induced dystonic extra-pyramidal reactions. Dent Clin North Am 2007; 51: 225–243.40. Balasubramaniam R, Ram S. Orofacial movement dis-orders. Oral Maxillofac Surg Clin North Am 2008; 20: 273–285.41. Clark GT, Ram S. Orofacial movement disorders. Oral Maxillofac Surg Clin North Am 2016; 28:397–407.42. Ghasemi N, Razavi S, Nikzad E. Multiple sclerosis: Pathogenesis, symptoms, diagnoses and cell-based therapy. Cell J 2017; 19:1–10. 237237References43. McDonnell GV. Clinical features of multiple sclerosis. In: Munsat TL (ed). Multiple sclerosis for the practicing neurologist. New York: Demos, 2007.44. O’Connor AB, Schwid SR, Herrmann DN, Markman JD, Dworkin RH. Pain associated with multiple sclerosis: Systematic review and proposed classication. Pain 2008; 137:96–111.45. Cruccu G, Biasiotta A, Di Rezze S, et al. Trigeminal neu-ralgia and pain related to multiple sclerosis. Pain 2009; 143:186–191.46. Halperin JJ. Nervous system Lyme disease. J R Coll Physicians Edinb 2010; 40:248–255.47. Halperin JJ. Neurologic manifestations of Lyme dis-ease. Curr Infect Dis Rep 2011; 13:360–366.48. Murphy MA, Szabados EM, Mitty JA. Lyme disease as-sociated with postganglionic Horner syndrome and Raeder paratrigeminal neuralgia. J Neuroophthalmol 2007; 27:123–124.49. Lobbezoo F, Ahlberg J, Glaros AG, et al. Bruxism de-ned and graded: An international consensus. J Oral Rehabil 2013; 40:2–4.50. Rompré PH, Daigle-Landry D, Guitard F, Montplaisir JY, Lavigne GJ. Identication of a sleep bruxism subgroup with a higher risk of pain. J Dent Res 2007; 86: 837–842.51. Ella B, Ghorayeb I, Burbaud P, Guehl D. Bruxism in movement disorders: A comprehensive review. J Prosthodont 2017;26:599–605.52. Lavigne GJ, Khoury S, Abe S, Yamaguchi T, Raphael K. Bruxism physiology and pathology: An overview for cli-nicians. J Oral Rehabil 2008; 35:476–494.53. Lavigne GJ, Montplaisir JY. Restless legs syndrome and sleep bruxism: Prevalence and association among Ca-nadians. Sleep 1994; 17:739–743.54. Ohayon MM, Li KK, Guilleminault C. Risk factors for sleep bruxism in the general population. Chest 2001; 119:53–61.55. Laberge L, Tremblay RE, Vitaro F, Montplaisir J. Devel-opment of parasomnias from childhood to early adoles-cence. Pediatrics 2000; 106:67–74.56. Ng DK, Kwok KL, Cheung JM, et al. Prevalence of sleep problems in Hong Kong primary school children: A community-based telephone survey. Chest 2005; 128:1315–1323.57. Lavigne GL, Lobbezoo F, Rompré PH, Nielsen TA, Montplaisir J. Cigarette smoking as a risk factor or an exacerbating factor for restless legs syndrome and sleep bruxism. Sleep 1997; 20:290–293.58. Hojo A, Haketa T, Baba K, Igarashi Y. Association be-tween the amount of alcohol intake and masseter muscle activity levels recorded during sleep in healthy young women. Int J Prosthodont 2007; 20:251–255.59. Winocur E, Gavish A, Voikovitch M, Emodi-Perlman A, Eli I. Drugs and bruxism: A critical review. J Orofac Pain 2003; 17:99–111.60. Saito M, Yamaguchi T, Mikami S, et al. Temporal associa-tion between sleep apnea-hypopnea and sleep bruxism events [epub ahead of print 4 Nov 2013]. J Sleep Res doi: 10.1111/jsr.12099. 61. Manfredini D, Landi N, Fantoni F, Segù M, Bosco M. Anxiety symptoms in clinically diagnosed bruxers. J Oral Rehabil 2005; 32:584–588.62. Pingitore G, Chrobak V, Petrie J. The social and psycho-logic factors of bruxism. J Prosthet Dent 1991; 65:443–446.63. Kato T, Lavigne GJ. Sleep bruxism: A sleep-related movement disorder. Sleep Med Clin 2010; 5:9–35.64. Macaluso GM, Guerra P, Di Giovanni G, Boselli M, Parrino L, Terzano MG. Sleep bruxism is a disorder re-lated to periodic arousals during sleep. J Dent Res 1998; 77:565–573.65. Klasser GD, Balasubramaniam R, Epstein J. Topical review-connective tissue diseases: Orofacial manifesta-tions including pain. J Orofac Pain 2007; 21:171–184.66. Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collabo-rating Clinics classication criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64:2677–2686.67. Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classication criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2010; 69: 1580–1588.68. Tabeling HJ, Dolwick MF. Rheumatoid arthritis: Diagno-sis and treatment. Fla Dent J 1985; 56(1):16–18.69. Delantoni A, Spyropoulou E, Chatzigiannis J, Papademi-triou P. Sole radiographic expression of rheumatoid ar-thritis in the temporomandibular joints: A case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 102:e37–e40.70. Kobayashi R, Utsunomiya T, Yamamoto H, Nagura H. Ankylosis of the temporomandibular joint caused by rheumatoid arthritis: A pathological study and review. J Oral Sci 2001; 43:97–101.71. Bayar N, Kara SA, Keles I, Koç MC, Altinok D, Orkun S. Temporomandibular joint involvement in rheumatoid arthritis: A radiological and clinical study. Cranio 2002; 20:105–110.72. Hirahara N, Kaneda T, Muraoka H, Fukuda T, Ito K, Kawashima Y. Characteristic magnetic resonance imag-ing ndings in rheumatoid arthritis of the temporoman-dibular joint: Focus on abnormal bone marrow signal of the mandibular condyle, pannus, and lymph node swell-ing in the parotid glands. J Oral Maxillofac Surg 2017; 75:735–741.73. Marini I, Vecchiet F, Spiazzi L, Capurso U. Stomato-gnathic function in juvenile rheumatoid arthritis and in developmental open-bite subjects. ASDC J Dent Child 1999; 66:30–35. 2381023810Extracranial and Systemic Causes of Head and Facial Pain74. Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism classication criteria for primary Sjögren’s syndrome: A consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis 2017; 76:9–16.75. Font J, Ramos-Casals M, de la Red G, et al. Pure sen-sory neuropathy in primary Sjögren’s syndrome. Long-term prospective followup and review of the literature. J Rheumatol 2003; 30:1552–1557.76. Urban PP, Forst T, Lenfers M, Koehler J, Connemann BJ, Beyer J. Incidence of subclinical trigeminal and facial nerve involvement in diabetes mellitus. Electromyogr Clin Neurophysiol 1999; 39:267–272.77. List T, Stenström B, Lundström I, Dworkin SF. TMD in patients with primary Sjögren syndrome: A comparison with temporomandibular clinic cases and controls. J Orofac Pain 1999; 13:21–28.78. Gökçay F, Oder G, Celebisoy N, Gökçay A, Sirin H, Kabasakal Y. Headache in primary Sjögren’s syndrome: A prevalence study. Acta Neurol Scand 2008; 118: 189–192.79. Spackman GK. Scleroderma: What the general dentist should know. Gen Dent 1999; 47:576–579.80. Scardina GA, Messina P. Systemic sclerosis: Descrip-tion and diagnostic role of the oral phenomena. Gen Dent 2004; 52:42–47.81. Wada T, Ram S. Limited mouth opening secondary to diffuse systemic sclerosis. Case Rep Dent 2013; 2013:937487.82. Van den Hoogen F, Khanna D, Fransen J, et al. 2013 classication criteria for systemic sclerosis: An Ameri-can College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 2013; 65:2737–2747.83. Ramon Y, Samra H, Oberman M. Mandibular condylosis and apertognathia as presenting symptoms in progres-sive systemic sclerosis (scleroderma). Pattern of man-dibular bony lesions and atrophy of masticatory mus-cles in PSS, presumably caused by affected muscular arteries. Oral Surg Oral Med Oral Pathol 1987; 63: 269–274.84. Crincoli V, Fatone L, Fanelli M, et al. Orofacial manifes-tations and temporomandibular disorders of systemic scleroderma: An observational study. Int J Mol Sci 2016; 17:E1189.85. Chaffee NR. CREST syndrome: Clinical manifestations and dental management. J Prosthodont 1998; 7:155–160.86. Wood RE, Lee P. Analysis of the oral manifestations of systemic sclerosis (scleroderma). Oral Surg Oral Med Oral Pathol 1988; 65:172–178.87. Nadeau SE. Neurologic manifestations of connective tissue disease. Neurol Clin 2002; 20:151–178.88. Fischoff DK, Sirois D. Painful trigeminal neuropathy caused by severe mandibular resorption and nerve compression in a patient with systemic sclerosis: Case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000; 90:456–459.89. Hupp SL. Giant cell arteritis associated with progres-sive systemic sclerosis. J Clin Neuroophthalmol 1989; 9:126–130.90. On AY, Aykanat D, Atamaz FC, Eyigor C, Kocanogullari H, Oksel F. Is it necessary to strictly diagnose bromy-algia syndrome in patients with chronic widespread pain? Clin Rheumatol 2015; 34:1473–1479.91. Sánchez-Domínguez B, Bullón P, Román-Malo L, et al. Oxidative stress, mitochondrial dysfunction and, inam-mation common events in skin of patients with bromy-algia. Mitochondrion 2015; 21:69–75.92. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in bromyalgia. Arthritis Rheum 2002; 46:1333–1343.93. Mease PJ, Arnold LM, Crofford LJ, et al. Identifying the clinical domains of bromyalgia: Contributions from cli-nician and patient Delphi exercises. Arthritis Rheum 2008; 59:952–960.94. Arnold LM, Clauw DJ, McCarberg BH, FibroCollabora-tive. Improving the recognition and diagnosis of bro-myalgia. Mayo Clin Proc 2011; 86:457–464.95. Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology preliminary diagnostic criteria for bromyalgia and measurement of symptom sever-ity. Arthritis Care Res (Hoboken) 2010; 62:600–610.96. Plesh O, Wolfe F, Lane N. The relationship between -bromyalgia and temporomandibular disorders: Preva-lence and symptom severity. J Rheumatol 1996; 23:1948–1952.97. Balasubramaniam R, de Leeuw R, Zhu H, Nickerson RB, Okeson JP, Carlson CR. Prevalence of temporoman-dibular disorders in bromyalgia and failed back syn-drome patients: A blinded prospective comparison study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 104:204–216.98. Scully C, Porter S. Orofacial disease: Update for the dental clinical team: II. Cervical lymphadenopathy. Den-tal Update 2000; 27:44–47.99. Parisi E, Glick M. Cervical lymphadenopathy in the den-tal patient: A review of clinical approach. Quintessence Int 2005; 36:423–436.100. Chiappini E, Camaioni A, Benazzo M, et al. Develop-ment of an algorithm for the management of cervical lymphadenopathy in children: Consensus of the Italian Society of Preventive and Social Pediatrics, jointly with the Italian Society of Pediatric Infectious Diseases and the Italian Society of Pediatric Otorhinolaryngology. Ex-pert Rev Anti Infect Ther 2015; 13:1557–1567.101. Weyand CM, Hicok KC, Hunder GG, Goronzy JJ. Tissue cytokine patterns in patients with polymyalgia rheu-matica and giant cell arteritis. Ann Intern Med 1994; 121:484–491.102. Wall M, Corbett JJ. Arteritis. In: Olesen J, Goadsby PJ, Ramadan NM, Tfelt-Hansen P, Welch KMA (eds). The Headaches, ed 3. Philadelphia: Lippincott Williams & Wilkins, 2006:901–910. 239239References103. Salvarani C, Hunder GG. Giant cell arteritis with low erythrocyte sedimentation rate: frequency of oc-curence in a population-based study. Arthritis Rheum 2001; 45:140–145.104. Kermani TA, Schmidt J, Crowson CS, et al. Utility of erythrocyte sedimentation rate and C-reactive protein for the diagnosis of giant cell arteritis. Semin Arthritis Rheum 2012; 41:866–871.105. Klein RG, Campbell RJ, Hunder GG, Carney JA. Skip lesions in temporal arteritis. Mayo Clin Proc 1976; 51:504–510.106. Carroll SC, Gaskin BJ, Danesh-Meyer HV. Giant cell ar-teritis. Clin Exp Ophthalmol 2006; 34:159–173.107. Sakaguchi M, Kitagawa K, Hougaku H, et al. Mechanical compression of the extracranial vertebral artery during neck rotation. Neurology 2003; 61:845–847.108. Zaina C, Grant R, Johnson C, Dansie B, Taylor J, Spyropolous P. The effect of cervical rotation on blood ow in the contralateral vertebral artery. Man Ther 2003; 8:103–109.109. Mitchell JA. Changes in vertebral artery blood ow fol-lowing normal rotation of the cervical spine. J Manipu-lative Physiol Ther 2003; 26:347–351.110. Mitchell J, Keene D, Dyson C, Harvey L, Pruvey C, Phillips R. Is cervical spine rotation, as used in the stan-dard vertebrobasilar insufciency test, associated with a measureable change in intracranial vertebral artery blood ow? Man Ther 2004; 9:220–227.111. Gayral L, Neuwirth E. Oto-neuroophthalmologic mani-festations of cervical origin; posterior cervical sympa-thetic syndrome of Barre-Lieou. N Y State J Med 1954; 54:1920–1926.112. Wight S, Osborne N, Breen AC. Incidence of ponticulus posterior of the atlas in migraine and cervicogenic headache. J Manipulative Physiol Ther 1999; 22:15–20.113. Foster CA, Jabbour P. Barre-Lieou syndrome and the problem of the obsolete eponym. J Laryngol Otol 2007; 121:680–683.114. Sarlani E, Balciunas BA, Grace EG. Orofacial Pain--Part II: Assessment and management of vascular, neurovas-cular, idiopathic, secondary, and psychogenic causes. AACN Clin Issues 2005; 16:347–358.115. Gladstone J, Bigal ME. Headaches attributable to infec-tious diseases. Curr Pain Headache Rep 2010; 14: 299–308.116. Celle ME, Carelli V, Fornarino S. Secondary headache in children. Neurol Sci 2010; 31(suppl 1):S81–S82.117. Matsuka Y, Fort ET, Merrill RL. Trigeminal neuralgia due to an acoustic neuroma in the cerebellopontine angle. J Orofac Pain 2000; 14:147–151.118. Trumpy IG, Lyberg T. Temporomandibular joint dysfunc-tion and facial pain caused by neoplasms. Report of three cases. Oral Surg Oral Med Oral Pathol 1993; 76:149–152.

Related Articles

2 Comments

  1. Tim Weber

    Im impressed, I must say. Really rarely do I encounter a blog thats both educative and entertaining, and let me tell you, you have hit the nail on the head. Your idea is outstanding; the issue is something that not enough people are speaking intelligently about. I am very happy that I stumbled across this in my search for something relating to this.

  2. Thomas

    I was very pleased to find this web-site.I wanted to thanks for your time for this wonderful read!! I definitely enjoying every little bit of it and I have you bookmarked to check out new stuff you blog post.

Leave A Comment?