MANIFESTATIONS OF SYSTEMIC DISEASE
to Grand Rounds Index|
Dept. of Otolaryngology, UTMB, Grand Rounds
James Grant, M.D.
B. Quinn, Jr., M.D.
Francis B. Quinn, Jr., M.D.
"This material was prepared by resident
physicians in partial fulfillment of educational requirements established for
the Postgraduate Training Program of the UTMB Department of Otolaryngology/Head
and Neck Surgery and was not intended for clinical use in its present form. It
was prepared for the purpose of stimulating group discussion in a conference setting.
No warranties, either express or implied, are made with respect to its accuracy,
completeness, or timeliness. The material does not necessarily reflect the current
or past opinions of members of the UTMB faculty and should not be used for purposes
of diagnosis or treatment without consulting appropriate literature sources and
informed professional opinion."
OF SYSTEMIC DISEASE
The otolaryngologist undoubtedly diagnoses
and treats various head and neck manifestations of an underlying systemic disease.
Indeed, pathology in this area may often be the initial marker for a larger disease
process. It takes diligence and a high degree of suspicion for the physician to
make the diagnosis. The systemic diseases may be a connective tissue disorder,
granulomatous disease, hematological / oncological disease, nutritional disorder,
metabolic disorder, neurological, or a systemic infectious disease.
CONNECTIVE TISSUE DISORDERS/GRANULOMATOUS
Characterized by an autoimmune induced
inflammatory reaction to the peripheral synovial joints, it typically affects
women more frequently than men in their fourth to fifth decade of life. Common
signs and symptoms include subcutaneous rheumatoid nodules, morning stiffness,
joint pain and swelling, and constitutional symptoms of malaise, fever, etc. Additionally,
there may be more serious cardiac involvement (such as pericarditis, myocarditis,
rheumatoid nodules in the myocardial tissue), cutaneous vasculitis, neurological
disease (mononeuritis multiplex), and diffuse pulmonary manifestations (pleural
effusion, pulmonary vasculititis).(1) Because of synovial joint involvement in
this disease process, the head and neck pathology is a direct consequence. The
joint spaces typically involved include the cricoarytenoid joint, the ossicular
joints, the temporomandibular joint space, and the cervical spine joint. Rheumatoid
involvement of the larynx is the most common, however, and may present as:
Temporomandibular joint dysfunction
may also be so severe that an anterior open bite deformity may exist. In addition,
these patients may have otologic complaints of hearing loss either conductive
secondary to synovitis of the ossicular joint or sensorineural from an autoimmune
related disorder of the inner ear. Involvement of the cervical spine may result
in disruption of the joint space with possible atlanto-occipital subluxation during
- (1) arthritis of the cricoarytenoid
- (2) laryngeal myositis,
- (3) ischemic atrophy of the
recurrent laryngeal nerves, and
- (4) rheumatoid nodules of the
Polymyositis / Dematomyositis
These disease entities are characterized
by an inflammatory myopathy that clinically presents as weakness, tenderness,
and progressive axial muscle wasting. The dermatomyositis variant has a distinct
heliotrope rash which is seen on the face. For the otolaryngologists, these patients
may complain of difficulty with phonation and deglutition secondary to involvement
of the tongue muscle, while they may also have nasal regurgitation from palatal
and pharyngeal muscle wasting. Dysphagia is also common as there is frequently
dysfunction with the superior constrictors, cricopharyngeus, and esophageal muscles.
Diagnosis of polymyositis / dermatomyositis is made by characteristic EMG findings,
elevated creatinine phosphokinase levels, and finding proximal muscle weakness.
Of note, there may be an underlying malignancy of the lung, prostate, ovary, uterus,
or colon in approximately 10% of these patients presenting with this systemic
This is another example of a diffuse
inflammatory disease with involvement of cartilaginous structures with progressive,
gradual replacement with granulation and fibrous tissue. Typically affecting females,
it generally occurs in the age range of 35 - 45. Systemically, it may affect any
cartilage structure, but also may have severe cardiovascular involvement of aortitis,
vasculitis, valvular insufficiency, and aneurysms in approximately 30% of the
affected patients.(5) In the head and neck region, the cartilaginous structures
of the ear and nose are commonly involved, with deformities related to tissue
destruction (i.e. saddle nose). In auricular chondritis, the lobule is spared
as is the external auditory canal; however, there is frequently a concomitant
serous otitis media. There may also be laryngeo-trachaeal involvement with the
possibility of later subglottic stenosis. It should be noted that in the adult
patient with a clinical finding of subglottic stenosis without an identifiable
cause, the physician should entertain the possibility of relapsing polychondritis,
sarcoidosis, or Wegener's granulomatosis.(6) Resolution of the polychondritis
may spontaneously resolve after a few days from the onset, otherwise anti-inflammatory
medications are the mainstay for symptomatic relief. Surgical reconstruction of
the nose or ear may later be indicated.
Classified into two subtypes, primary
Sjogren’s syndrome is also referred to as the sicca complex (keratoconjunctivitis
plus xerostomia), while secondary Sjogren’s syndrome is associated with another
connective tissue, usually rheumatoid arthritis. This a chronic disease of immune
mediated destruction of exocrine glands with resulting desiccation of the associated
mucous membranes. There is a predisposition based on the major histocompatibility
complex as approximately 90% of the females affected with primary Sjogren's are
HLA B8 and HLA DR3. The clinical manifestations include severe gingivitis, dental
caries, periodontal disease secondary to xerostomia, while corneal ulceration
may be noted secondary to keratoconjunctivitis. There may also be generalized
parotid swelling secondary to lymphocytic infiltration. In addition, there may
tongue atrophy/glossitis and extensive nasal crusting with epistaxis from the
dry mucous membranes. Systemic manifestations include gastric atrophy, pancreatic
insufficiency, pericarditis, neuropathy, and pleuritis.(7) Of importance, these
patients have 44 times relative risk of non-Hodgkin's lymphoma and should be considered
especially in light of a patient with a rapidly enlarging parotid gland.(8) Diagnosis
is based on finding xerostomia/xerophthalmia, associated connective tissue disease,
and noted lymphocytic infiltration in a minor salivary gland biopsy.
This is rare disease that is marked
by deposition of extracellular fibrillar protein in various tissues. There are
several variants of this disease. There are two forms of systemic amyloidosis,
primary and secondary. In primary systemic amyloidosis, the areas generally affected
are the heart, tongue, and gastrointestinal tract, while in secondary systemic
amyloidosis, there is an underlying chronic inflammatory disease such as tuberculosis,
osteomyelitis, or rheumatoid arthritis and the tissues usually involved are the
spleen, adrenals, liver, and kidneys. In the localized form of amyloidosis, the
amyloid deposits are contained in a specific anatomical region, such as isolated
tongue involvement. Finally, there is a systemic form of amyloidosis associated
with multiple myeloma, where the tissues affected are the same as in primary systemic
amyloidosis.(9) In the head and neck region, the tongue is the most site of amyloid
deposition, with 12% of the patients having severe macroglossia. The larynx may
also be involved with the ventricle being the most common followed by false vocal
cords, aryepiglottic folds, and the subglottic region.(10) Diagnosis is based
on microscopic exam of biopsied material showing green, bifringement particles
under polarized light after staining with Congo red. Treatment is by excision
of symptomatic deposits.
This is a disease of young adults that
presents after an otherwise unremarkable upper respiratory infection. While it
may be linked to an autoimmune reaction to the organism Chlamydia trachomatis,
its cause is uncertain. It has systemic manifestations of aortitis, aortic valve
insufficiency, pleuritis, pericardial effusion, coronary arteritis, and possibly
myocardial infarction. In the head and neck, it is seen as a nonsyphilitic interstitial
keratitis and bilateral audiovestibular symptoms such as fluctuating hearing loss,
vertigo, tinnitus, and aural fullness. In a small percentage of the patients,
there may be progression to complete absence of vestibular function with ataxia
and oscillopsia. Diagnosis is clinical with the finding of increased titers to
Chlamydia, while treatment with steroids has been shown to hasten the symptoms.(11)
This is a granulomatous disorder of
unknown etiology which typically affects black females between the ages of 30-50.
It is seen as multi-system disease, with the histological trademark of non-casseating
granulomas as discrete lesions. It also has several characteristic laboratory
findings such as hypercalcemia, hypergammaglobulinemia, elevated liver transaminases,
and elevated levels of angiotensin converting enzyme which may allow objective
clinical following of response to therapy. The most common site of involvement
is by far pulmonary (88%) followed by lymphatic in 75% of the patients.(12) The
chest x-ray will typically show hilar adenopathy. Other systemic manifestations
include splenomegaly, diffuse neuropathies, intracranial mass involvement, and
ocular pathology (optic neuritis). In the head and neck region, submandibular/submental/cervical
adenopathy is frequently. The salivary glands are involved in approximately 20
-30% of the cases, showing either diffuse enlargement of granuloma infiltration.
As a distinct clinical entity, Heerfordt's syndrome (a.k.a. uveoparotid fever)
is seen as facial nerve paralysis, uveitis, and bilateral parotid swelling. The
supraglottic region is also frequently affected with examination often revealing
a pale, bluish, enlarged epiglottis as well as edematous, erythematous nodular
masses along the mucosa. In addition, the paranasal sinuses, nose, and nasopharynx
is involved in 10 - 20% of the patients with polypoid mucosa, nodular masses,
and significant crusting. Diagnosis is made on biopsy specimens showing the non-casseating
granulomas. Treatment ranges from observation in the asymptomatic patient to high
This is an autoimmune disease that
is manifest as systemic necrotizing granulomas and vasculitis with a predilection
for the upper and lower respiratory tracts and renal system. The pulmonary symptoms
are almost universal with cough and hemoptysis, whereas the renal system is affected
in approximately 40-50% of the cases, manifest as a focal glomerulonephritis.(14)
Central and nervous system involvement is also seen in 20-30% of the cases, usually
seen as polyneuritis, meningitis, or mononeuritis mulitplex. In the head and neck
region, the paranasal sinuses/nose are the most frequently affected (60-80%) with
chronic sinusitis, severe nasal crusting, septal perforation, and granulomatous
destruction of tissue in these areas. While not as common, otological manifestations
range from a serous otitis media to a severe sensorineural hearing loss secondary
to cochlear vasculitis. Less commonly, subglottic stenosis may be seen in 8% of
these patients.(15) Diagnosis is based on clinical findings, biopsy of involved
tissue showing necrotizing granulomas/vasculitis, and laboratory evidence of c-
ANCA. Treatment has been somewhat successful with prednisone, cyclophosphamide,
and recently with trimethoprim/sulfamethoxazole.
This is vasculitic disease that involves
small and medium size arteries that usually involves those vessels supplying the
tissues of the gastrointestinal tract, hepatobiliary system, kidney, pancreas,
and skeletal tissues. The tissues involved undergo ischemia and necrosis secondary
to the vasculitic process and manifest as myopathy, neuropathy, hepatic and renal
failure, gastrointestinal bleeding, and progressive arthritis. In general, there
are few head and neck manifestations; however, ischemia to the nasal and oral
cavity/oral pharynx mucosa may cause ulceration. In addition, these patients may
have serous otitis media, sensorineural hearing loss, and facial nerve paralysis.(16)
As a variant of polyarteritis nodosa,
this disease is marked by allergic angiitis granulomatosis, asthma, and peripheral
eosinophilia. The pulmonary system is almost invariably involved with 70% of these
patients having nasal involvement, seen as nasal polyposis and allergic rhinitis.(17)
This disease has three distinct clinical phases seen as:
- (1) prodromal phase that persists
for years and is seen as allergic disease;
- (2) peripheral blood and tissue
eosinophilia, chronic eosinophilic pneumonia, and eosinophilic gastroenteritis;
- (3) life-threatening systemic
vasculitis.(18) This disease entity is different from Wegener's granulomatosis
as asthma and eosinophilia are distinct for Churg-Strauss Syndrome, as well
as the lack of renal involvement.
These are considered to by the same
disease process. Histologically, they are characterized as an angiocentric infiltration
of mature lymphocytes, immunoblasts, plasma cells, histiocytes, and a few atypical
lymphoid cells. There is no accompanying granuloma or vasculitis. This distinguishes
this disease entity from the vasculitides (such as Wegener's) in that there is
no vessel destruction. While controversial, these disease may represent a precursor
to a frankly malignant T-cell lymphoma. Systemically, many systems are involved
including the central nervous system, pulmonary, renal, and the gastrointestinal
tract. Regarding the head and neck manifestations, the early manifestation consists
of a unilateral, localized ulceration of the nose or paranasal sinuses. This locally
explosive ulcer progresses rapidly in its destruction to involve the adjacent
sinuses, orbit, and palate. Rapid ulceration and necrosis generally results in
spiking fevers and sepsis. While Wegener's granulomatosis also causes paranasal/nasal
tissue destruction, it presents as a bilateral process, not unilateral. Diagnosis
depends on biopsy. Treatment consists of radiation therapy in more localized disease
to chemotherapy following a lymphoma protocol for disseminated disease.(19)
Osler-Weber-Rendu (Hereditary Hemorrhagic
Transmitted as an autosomal dominant
trait, this disease is characterized by telangiectatic lesions developing around
puberty. Common sites include the gastrointestinal tract, the lungs and liver
which may contain multiple, larger arteriovenous malformations, and in multiple
areas in the head and neck regions. The nasal septum as well as the lateral nasal
wall are frequently affected by these lesions which often results in frequent,
severe episodes of epistaxis. In these patients, they may have gross destruction
of the nasal septum secondary to the need for cauterization at the bleeding sites.
Additionally, the nasal mucosa may be so involved with the lesions that septodermoplasty
is often indicated. The lips and dorsum of the tongue are also involved in 60%
of the cases; whereas, the palate, gingiva, buccal mucosa, and mucocutaneous junction
is involved in approximately 20% of the cases.(20)
Acute Myelocytic Leukemia/Acute
Head and neck manifestations from leukemia
are many fold. Epistaxis may occur secondary to thrombocytopenia or to a coagulopathy
from liver infiltration. The temporal bone is also a well documented site of involvement,
showing infiltration in the submucosa of the pneumatized area of the middle ear
and mastoid, including the tympanic membrane and petrous apex.(21) Thus, these
patients may present with otomastoiditis (chronic versus acute), tympanic membrane
thickening, hearing loss, vertigo, and facial nerve paralysis. Gingival hyperplasia
secondary to myeloid infiltration has been described for AML, while the lymphoid
bearing tissues may be involved with ALL, especially the tonsils. Petechia and
hemmorhagic lesions may also be noted in the oral cavity secondary to thrombocytopenia.
As a distinct clinical entity, agranulocyte angina is marked as extreme pain in
the oral cavity with a relatively unremarkable clinical examination.
Lymphoma is the most common form of
pediatric malignancy, many presenting to the otolaryngologist initially because
of head and neck involvement. Hodgkin's lymphoma is typically found in young adults
or adolescents and is characterized as a lymphoreticular malignancy with Reed-Sternberg
cells. These cells are seen as large, multi-nucleated cells having perinucleolar
halos and eosinophilic cytoplasm. This disease begins in a single lymph node and
then progresses in a contiguous pattern. The major head and neck manifestation
of Hodgkin's lymphoma is the presence of painless lymphadenopathy in the cervical,
supraclavicular, and mediastinal areas.(22) While adenopathy is clearly the most
common manifestation, extranodal involvement occurs in 10% of cases (Hodgkin's
and Non-Hodgkin's) includes infiltrates in tonsil (40%), nasopharynx (18%), paranasal
sinuses/nose (13%), oral cavity (10%), salivary gland (9%), and base of tongue
(8%).(23) Non-Hodgkin's lymphoma, as contrasted to Hodgkin's, is more commonly
a disease of pre-adolescent children with involvement of the lymphatics in a non-contiguous
fashion. In addition, there is often evidence of disseminated disease at initial
presentation, with only a small percentage having head and neck manifestations.
There are three histologically distinct subtypes: undifferentiated (Burkitt's
and Non-Burkitt's lymphoma), lymphoblastic, and large cell. In these lymphomas,
the lymphoid tissue of Waldeyer's ring may be involved.
This syndrome has been referred to
as sideropenic dysphagia and is a disease entity marked by dysphagia, hypopharyngeal
and esophageal webs, weight loss, and iron deficiency anemia. It usually affects
females in the 30-50 year old age group.(24) The otolaryngological manifestations
include atrophic glossitis secondary to atrophy of the filiform papillae, angular
chelitis, and hyperkeratotic lesions on the oral mucosa. The webs in the hypopharynx
are typically between the cricoid and the thoracic esophagus. They begin as anteriorly
located webs but become circumferential. There is an increased incidence of carcinoma
located proximal to the webs, likely secondary to chronic inflammation in this
This is a disease entity seen as a
disorder of uric acid metabolism, which typically results in an episodic, self-limited
monoarticular arthritis. While head and neck manifestations are rare, gouty arthritis
and tophaceous deposits may manifest in this area. Involvement of the cricoarytenoid
joint presents as dysphagia, pain, hoarseness, and possibly stridor/airway obstruction
depending on possible fixation of the cord. The helical rim of the pinna is the
usual location of involvement the tophaceous deposit, which is marked as uric
acid crystals with associated foreign body reaction
Hypothyroidism has several causes but
the clinical manifestations of having reduced levels of thyroid hormone produces
a similar clinical picture. Systemic symptoms and signs consist of myxedema, muscle
cramps, impaired memory, lethargy, constipation, cold intolerance, bradycardia
with associated EKG changes, and prolonged reflexes. For the otolaryngologists,
these patients may present with hoarseness secondary to myxedema of the vocal
cords, nasal obstruction secondary to edema of the nasal mucosa, alopecia which
may affect the lateral third of the eyebrows, and a thickened tongue. Hyperthyroidism
also has several head and neck manifestations. The systemic manifestations includes
hyperreflexia, heat intolerance, anxiousness, and cardiac arrhythmias, Regarding
the head and neck region, thyroid exophthalmos is seen in Grave's disease. In
addition to the exophthalmos , there may be decreased ocular motility. The ocular
pathology is secondary to an infiltration of the muscles and periorbital tissues
with an abnormal mucopolysaccharide substance as well as a lymphocytic infiltration.(25)
Poorly controlled diabetics are at
greater risk of opportunistic type infections, secondary to granulocyte qualitative
dysfunction. For instance, these patients may present with oral cavity/pharyngeal
candidiasis. These patients may complain of vertigo/dizziness, usually related
to elevated blood sugar as well as to autonomic dysfunction causing severe orthostatic
hypotension, and may have a sensorineural hearing loss secondary diabetic micorangiopathy.
Of special importance for the otolaryngologist is the clinical entity of malignant
(necrotizing) otitis externa caused by Pseudomonas aeriginosa. The infection starts
after only minor trauma to the external canal which later manifests as severe
otalgia. Examination of the affected ear shows signs of inflammation, with redness,
swelling, and tenderness. In addition, there may also be an area of granulation
tissue located at the floor of the ear canal along the junction of the bony and
cartilaginous portions, representing osteitis of the lateral lip of the tympanic
bone.(26) Later stages of malignant otitis externa may present with cranial nerve
palsies secondary to cranial base osteitis. In addition, the infection may spread
posteriorly to the stylomastoid foramen causing facial nerve paralysis. Treatment
consists of meticulous control of the diabetes, intravenous antibiotics (usually
an aminoglycoside and a semisynthetic penicillin), antibiotic ear drops, and debridement
of infected tissue. Hyperbaric oxygen therapy has also been proven to improve
the healing time.
Multiple sclerosis is a demyelinating
disease of the central nervous system that has a remitting and exacerbating course.
In approximately 20% of the patients, the initial manifestation of multiple sclerosis
is blurred or loss of vision secondary to demylientation of the optic nerve. Additionally,
internuclear ophthalmoplegia is another early manifestation secondary to demylientation
of the medial longitudinal fasiculus , which is seen as the inability to attain
conjugate gaze because the lateral rectus and contralateral medial rectus are
incoordinated. Vertigo is also a frequent finding in this disease, affecting up
to 50% of the patients with multiple sclerosis and being the initial manifestation
in 7-10% of these patients. It should be noted that while the nystagmus, usually
horizontal, is found in 70% of the patients, but the finding of pendular fixation
nystagmus is helpful in that it is rarely found with other pathology.(27) With
regard to nystagmus, it is a component of Charcot's triad in multiple sclerosis,
along with scanning speech (dysarthria secondary to cerebellar involvement) ,and
an intention tremor.(28) Hearing loss may be found in up to 10% of the patients.
Diagnosis of MS depends on the MRI to identify foci of demyelination within white
matter; whereas, laboratory analysis may reveal elevated gamma globulin levels
and elevated myelin basic protein. There is no definitive treatment of MS, although
steroids and adrenocorticotropic hormone have been found to hasten the remission
of the clinical manifestations.
Likely an autoimmune disease caused
by IgG directed at acetylcholine receptors, this disease is marked by weakness
and fatigue of the striated muscles. Marked by frequent remissions and exacerbations,
these patients will demonstrate symptoms resulting from weakened facial, laryngeal,
and pharyngeal muscles. Dysphagia may be a presenting complaint as the cricopharyngeus
is frequently involved. The diagnosis may be made with relief of muscle weakness
after the administration of edrophionium which inhibits acetylcholinesterase which
then allows an increased amount of acetylcholine at the receptor site. Treatment
is directed at using anticholinesterase medications, such as pyridostigmine. It
should be mentioned that in approximately 10% of these patients with MG, there
may be an associated thymoma.(29)
This is an acute, fulminant polyneuropathy
which usually has a preceding viral illness approximately 1-3 weeks earlier; although,
in approximately 5-10% of the reported cases, a surgical procedure took place
1-4 weeks prior to the onset of disease.(30) Of those felt to be virally induced,
herpetic infections (cytomegalovirus and Epstein-Barr virus) are believed to account
for a large number of the cases. The clinical features of Guillian-Barre syndrome
is an areflexic motor paralysis with mild sensory disturbances. Approximately
25% of these patients require mechanical ventilation secondary to diffuse involvement
of the muscles of respiration, but the overall prognosis is excellent with 85%
of the patients making complete or nearly complete recovery. Regarding the head
and neck manifestations, facial nerve paralysis may also be seen with this syndrome
and may be bilateral. The Fisher variant of Guillian-Barre syndrome begins with
weakness of the facial and neck muscles prior to limb weakness, as opposed to
the usual later manifestation. Treatment consists of supportive care with some
success with the use of plasmapheresis.(31)
Amyotrophic Lateral Sclerosis
This is a disease characterized by
progressive loss of motor neurons in the motor cortex and in the anterior horn
cells in the spinal cord. Generally, it is found in patients over the age of 50,
with men being more frequently affected. Its first manifestations are asymmetric
muscle weakness, fatigue, and cramping. As the disease progresses, virtually every
muscle group will show signs of weakness and later atrophy. In the head and neck
region, muscular dysfunction will cause a variety of problems of the patient.
For instance, the patient may have difficulty with mastication, deglutition, and
facial movement. The involved muscle groups show signs of atrophy and fasiculations
as the disease continues. This disease is relentlessly progressive without any
Deficiency may result from either endemic
lack of this vitamin in the diet or form protein-calorie malnutrition which results
in a defective release from the liver of retinol-binding protein.(32) The initial
manifestation is that of night blindness later followed by degenerative changes
of the retina and necrosis of the cornea (keratomalacia) with subsequent lens
extrusion. Stomatitis and xerostomia are also frequent manifestations.(33)
Hypovitaminosis B1 (Thiamine)
Deficiency of thiamine is marked by
the clinical syndromes of beriberi and the Wernicke-Korsakoff syndrome. In beriberi,
a "wet" form exists in which the patient may has clinical evidence of congestive
heart failure with diffuse edema, and a "dry" form in which the central and peripheral
nervous system is principally involved. The dry beriberi is seen as a peripheral
neuropathy in which the patient may have serious gait instability and dysequilibrium
that may be construed as vertigo. In addition, the distal extremities have sensory
loss. Beriberi generally occurs in rice-predominate diets. On the other hand,
the Wernicke-Korsakoff syndrome is typically seen in alcoholics who typically
have a protein poor/carbohydrate rich diet It is seen as marked by memory loss
of the immediate past which results in confabulation. Regarding the head and neck
manifestations, these patients may present with Wernicke's encephalopathy which
is seen as nystagmus (usually horizontal), lateral rectus muscle palsies, and
diplopia. These patients may also have ataxia, fever, progressive mental deterioration,
and profound emesis.(34)
Niacin/Nicotinic Acid Deficiencies
Deficiencies of nicotinic acid produce
clinical findings collectively referred to as pellegra. It is a chronic wasting
disease associated with dermatitis, diarrhea, and dementia. For the otolaryngologists,
this deficiency produces a widespread inflammation of the mucosal surfaces which
leads to glossitis, angular stomatitis, and cheilosis. Burning tongue pain is
often the first clinical sign of niacin deficiency. This inflammatory reaction
of the mucosal surfaces also explains the diarrhea associated with pellegra.
Deficiency of Riboflavin
This deficiency is characterized by
its oral manifestations. This syndrome is characterized by sore throat, hyperemia
and edema of the pharyngeal and oral mucous membranes, cheilosis, angular stomatitis,
and glossitis. In addition, these patients may also have seborrheic dermatitis
and normocytic anemia secondary to red cell hypoplasia of the bone marrow.(35)
Vitamin B12 Deficiency
Deficiency of this vitamin is seen
systemically as a megaloblastic anemia, which may also be seen with folic acid
deficiency. Clinically, these patients often present with painful atrophy of their
oral mucosa, lingual papillae, and tongue. In addition, they may have recurrent
aphthous ulcerations in the oral cavity.(36)
Disease caused by Mycobacterium tuberculosis
is spread from person to person by inhalation of an airborne droplet containing
the organism. In the overwhelming majority of the patients, the primary infection
is asymptomatic; however, inoculation initiates an inflammatory response with
a cell mediated hypersensitivity component developing over time. It is this immune
response that sequesters the tubercle bacilli and prevents multiplication or spread.
The healing process occurs, leaving a calcified granuloma referred to as a ghon
complex (in conjunction with hilar lymph node). In approximately 95% of those
exposed, the disease is limited; however, in 5% of the patients, the clinical
manifestations of tuberculosis occur, likely re-activated at a later time. The
clinical manifestations of TB are extensive, but pulmonary disease is an integral
component. Regarding the head and neck manifestations, cervical lymphadenopathy
is the most common and is referred to as scrofula. The lymph nodes are multiple,
matted, and non-tender, with usual bilateral involvement of the posterior triangles.
The larynx is involved in approximately 1% of the patients, likely secondary to
bronchogenic spread. The arytenoids are involved with the greatest frequency followed
by the true vocal cord, epiglottis, false vocal cord, and the subglottic area.
The lesions may be edematous, granulomatous, or ulcerated. Oral cavity lesions
(tuberculomas) are found in 0.5 to 1.5% of the patients with the tongue being
the most frequently affected (50%). Although far less common, otologic involvement
may be seen as multiple tympanic membrane perforations accompanied by a thin,
watery otorrhea. Diagnosis requires PPD, chest x-ray, and sputum showing acid
fast bacilli. Treatment is with anti-tuberculosis agents
Caused by M. kansaii, M. scrofulaceum,
M. intracellularis, and M. fortuitum. Transmission is from soil to mouth and eye.
Usually affecting children, a corneal ulceration is the usual manifestation followed
by scrofula in the anterior cervical, preauricular, and submandibular regions.
The lymph nodes are discrete, separate, and have the potential to form an abscess.
Diagnosis is by excisional biopsy of the involved lymph node, with cultures and
staining showing the bacilli. Treatment consists of anti-tuberculous agents/antibiotics,
dependent on the culture sensitivities.
Causes leprosy (Hansen's disease) which
is far more prevalent in tropical climates. There is a spectrum of disease ranging
from a tuberculin form to the lepromatous form. The tuberculoid form consists
of granulomatous involvement of the peripheral nerves producing severe myalgias
and muscle atrophy. In this setting, the facial nerve may also be involved. In
contrast, the lepromatous form has no neurological involvement but is classically
seen as widespread cutaneous lesions. These mucosal lesions may cause septal perforations
as well as destruction of support mechanisms of the nose. Lateral loss of the
eyebrows are a common finding. Diagnosis is through culture of involved tissue,
demonstrating the organism. Treatment is usually with dapsone.(37)
Caused by the spirochete Treponema
pallidum, this disease has several head and neck manifestations correlating with
the specific stage of the disease. In the primary stage, a painless ulcer exists
at the site of innoculum. While the chancre is typically located in the genital
area, it may found on the lips, tongue, or tonsil. During the secondary stage,
mucocutaneous lesions predominate. These may be found in the oral cavity/oral
pharynx and along the nasal mucosa. Other manifestations during this stage includes
rhinitis, laryngitis, pharyngitis, otitis media, and alopecia. This stage then
spontaneously resolves but has the potential to recur at a later time. The tertiary
stage occurs in 1/3 of the patients with syphilis and is marked by the gumma lesion
which represents the granulomatous reaction to the organism. Nasoseptal involvement
occurs commonly, resulting in perforation or saddle nose deformity, as is hard
palate perforations. Ulcerations in the larynx may also occur resulting in chrondritis/perichondritis
from secondary bacterial infection. The temporal bone is affected when the gummatous
lesion produces an obliterative endarteritis. There is gradual loss of the membranous
labyrinth resulting in sensorineural hearing loss seen as fluctuating, bilateral,
and sudden with possible accompanying vertigo. For the clinician, there are two
signs which may be present reflecting the underlying pathology of softening of
the otic capsule. Hennebert's sign shows nystagmus and vertigo as positive pressure
is applied to the ear canal, while Tulio's phenomenon is seen as nystagmus following
exposure to loud noise. Congenitally acquired syphilis has its own set of clinical
manifestations including a saddle nose deformity, frontal bossing, short maxilla,
Hutchinson's incisors, mulberry molars, mental retardation, and sensorineural
hearing loss. In congenital syphilis, a triad of SNHL, interstitial keratitis,
and notched incisors is referred to as Hutchinson’s triad. Treatment consists
of penicillin G.
Caused by Borellia burgdorferi and
spread through a tic vector, this disease is endemic to the Northeastern portion
of the United States. Clinically, at the site of innoculation an annular, expanding
red lesion may be found, referred to as erythema chronicum migrans. The course
is then marked as malaise, fever, myalgias, generalized lymphadenopathy, oligoarticular
arthritis (45%), cardiac conduction abnormalities secondary to myocarditis (8%),
possible encephalitis or radiculoneuritis and cranial neuropathies. Of interest
to the otolaryngologist, facial nerve paralysis may be unilateral or bilateral
and associated with other cranial neuropathies, such as CN III and CN V. It has
been found that most of these neuropathies will generally resolve in 6 12 months;
however, treatment with beta lactamase antibiotics that may decrease the overall
time for resolution.(39)
Cat Scratch Disease
This is caused by an intracellular,
gram negative bacilli which requires special staining (Warthin-Starry) for detection.
Cat exposure is identified in a large number of cases. It is generally found only
in children. The clinical manifestation is that of a vesicular, papular , or pustular
lesion at the site of innoculation with regional lymphadenopathy. In the head
and neck region, cervical lymphadenopathy is commonly found. Histologically, a
non-casseating granulomatous type reaction may be found. This disease is self-limited,
with incision and drainage as needed for severe abscess formation. In general,
the mass will resolve in 2-6 months.
Classed between a bacteria and a fungi,
Actinomyces israelli is a micoraerophillic gram-positive organism that is a normal
oral inhabitant (especially in the tonsillar crypts). It may produce a granulomatous
suppurative cervical adenitis or a cervicofacial infection. In the cervicofacial
form, there is typically an indurated, non tender subcutaneous mass in the anterior
cervical or submandibular triangle with multiple draining sinus tracts. Infection
appears to be promoted by those patient with severe periodontal disease and dental
caries. The systemic complaints are frequent with fever, weight loss, vomiting,
night sweats, and general malaise. Demonstration of sulfur granules on microscopic
examination makes the diagnosis. These are granules are tangle of filaments of
tissue cells and lipid-laden macrophages. Treatment consists of long-term parenteral
antibiotics with surgical debridement necessary in extreme cases to remove necrotic
Caused by inhalation of spores of Aspergillus
fumigatus, a ubiquitous fungus, it usually causes a self-limiting acute pneumonitis
in an otherwise healthy patient. It may, however, present as a systemic disease
with major otolaryngological manifestations and may be classified as allergic,
non-invasive, and invasive. In the allergic form, it appears as an analogue to
the allergic bronchopulmonary aspergillosis. It accompanies and exacerbates asthma
and clinically is seen as thick, tenacious nasal secretions with demonstrable
calcifications on CT scan. The epithelium and bone of the involved sinus is spared,
with the fungus localized to the overlying blanket of mucus. Non-invasive aspergillosis
presents as a unilateral sinusitis with extremely thick secretions, but without
the clinical evidence of bony erosion or asthma. In the immunocompromised host,
the invasive form of aspergillosis may be found. There is facial hypesthesia,
opthalmoplegia, proptosis, bony loss and destruction as seen on CT scan, and possible
visual loss. Of note, an aspergilloma may be found within a cavitated pulmonary
lesion or may be found within a sinus, especially the maxillary sinus. Treatment
of aspergillosis is surgical debridement with use of intravenous amphotericin
B. In allergic aspergillosis, the disease may be ameliorated with systemic steroids.(40)
The HIV/AIDS patient presents to the
otolaryngologist with a multitude of problems in the head and neck, including
frequent acute infections of the normal human pathogens, opportunistic infections,
neurological complaints, and neoplastic processes. As the degree of immunodeficiency
increases, the spectrum of disease that involves the head and neck also increases.
Several dermatological conditions affect
the face and scalp region in the infected patient. Molluscum contagiosum is often
seen in the symptomatic HIV positive patient. It is characterized by small pearly,
umbilicated papules that have a predilection for the eyelids. Treatment consists
of excision versus cryotherapy. Another common skin disorder is seborrheic dermatitis
that is often found on the scalp and face, affecting approximately 83% of these
patients.(41) These lesions are white scaly plaques or patches that may have an
element of erythema or inflammation. Bacillary angiomatosis is found in the more
immunosuppressed HIV patient and requires histology for diagnosis as an organism
is rarely cultured. This lesion is often found on the face and presents as a non-specific
subcutaneous nodule or as a friable papule. Oral erythromycin is an effective
treatment. Herpes zoster may present in a specific dermatomal pattern on the head
or neck. If the geniculate ganglion is involved in the herpetic infection, the
Ramsay Hunt syndrome is seen and is manifest as vesicles on the ear, oral mucosa,
tonsils, pharyngeal mucosa, posterior third of the tongue, facial palsy, loss
of taste, decreased salivation, palatal paralysis, and pain.(42) Acyclovir is
the treatment for this viral infection. Rarely, the HIV/AIDS patient may present
with pustular or granulomatous lesions involving the skin of the head and neck
that represent cutaneous Cryptococcus on histopathologic or culture identification.
Finally, Kaposi's sarcoma is often manifest as violaceous papular or ulcerated
skin lesions on the head and neck. While the gold standard for treatment of this
neoplasm is controversial, the Argon and CO2 lesions have been helpful in control
of local disease as well as low-dose radiation therapy, chemotherapy (i.e. vincristine
or vinblastine), and immunotherapy (i.e. alpha-interferon).
Several otological conditions also
affect the HIV/AIDS patient. While the external auditory canal is often affected
by some of the dermatological problems discussed above, such as Kaposi's sarcoma
and seborrheic dermatitis, more often this subset of patients are affected by
serous and acute otitis media. In the pediatric population with an already altered
eustachian tube function coupled with a depressed immune system, they have an
increased risk of middle ear infection. In the adult patient, adenoid hypertrophy
that often occurs with this disease increases the likelihood of eustachian tube
dysfunction, therefore contributing to an increase in otitis media. In addition
to the normal pathogens for middle ear disease, patients with AIDS may harbor
Pneumocystis carnii, candida, staphylococcus, or pseudomonas on tympanocentesis.
Although not clearly understood, several patients may have a mild to moderate
sensorineural hearing loss perhaps secondary to a central or peripheral nervous
system viral infection.(43)
The nose and paranasal sinuses are
also frequent sites of pathological processes in the HIV/AIDS patient. A common
complaint is nasal obstruction and thick postnasal rhinnorhea. This may be secondary
to allergic rhinitis of which these patients often have a hyperactive allergic
response, nasopharyngeal lymphoid tissue hypertrophy, or a neoplastic process
in the nose or nasopharynx (i.e. Kaposi's sarcoma, lymphoma). In addition, acute
and chronic sinusitis is often a problem caused by the usual pathogens as will
as more unusual ones as the immunusupression increases, such as legionella, candida,
ORAL CAVITY DISORDERS
The oral cavity and oropharynx are
also a frequent area displaying disease in these immunosuppressed patients. Oral
cavity/pharynx candidiasis infection is the most common manifestations of HIV/AIDS
infection. The most common form of oral candidiasis is pseudomembranous candidiasis
(a.k.a. thrush) that is characterized by plaques that may be easily removed, leaving
an erythematous base. The less common form is the atrophic candidiasis that is
seen as flat, atrophic patches on the tongue, palate, or buccal mucosa; whereas,
the candida leukoplakia is seen as hyperkeratotic lesions that may not be mechanically
removed. Angular chelitis is seen as erythematous fissures in the corner of the
mouth which is often seen in patients with oral candida infection. Diagnosis is
based on the basic examination along with a KOH prep if needed, while treatment
consists of a basic topical solution of nystatin to oral or parenteral anti-fungals.
Stomatitis caused by herpetic lesions versus aphthous ulcers are also common.
Herpetic stomatitis is seen as several ulcerative, punched out lesions occurring
on any mucosal surface, but with a predilection for the palatal, labial, buccal,
or gingival surfaces. These may coalesce to form an extremely large ulcerative
lesions. Acyclovir and topical steroids help to attenuate the local symptoms.
Aphthous ulcers are non-viral in
orgin, typically single, and usually found on "mobile" mucosal surfaces. Steroid
therapy (topical versus intralesional) may alleviate local symptoms. Hairy leukoplakia
is a lesion that is noted seen almost exclusively in the HIV infected patient
and is seen as a corrugated, whitish lesion along the anterior lateral border
of the tongue. Therapy is not usually indicated unless it becomes secondarily
infected; however, it is a relatively reliable prognosticator for the development
of AIDS (50 % at 16 months/80% at 30 months). Lymphoid hyperplasia in Waldeyer's
ring is often found in the patients.
Of note, malignancies such as lymphoma
(non-Hodgkin's>>>Hodgkin's) may be harbored in these tissues, especially in
the patient with an ulcerated lesion on the tonsil or tonsillar asymmetry. Other
neoplasm's within the oral cavity/oral pharynx in the HIV/AIDS patient is the
previously described Kaposi's sarcoma. These have a violaceous color, may be
flat or nodular, and have a predilection for the hard palate. Finally, the immunosuppressed
patient may have aggressive periodontal disease that may result in a necrotizing
ulcerative gingivitis with associated gingival recession. Treatment is directed
at diligent oral hygiene with frequent anti-bacterial mouthwashes and prophylactic
SALIVARY GLAND DISORDERS
Salivary gland disease is also frequently
seen. The spectrum of disease ranges from xerostomia with histolopathologic findings
similar to Sjogren's syndrome, to generalized parotid gland enlargement (reported
in 30% of the pediatric population) secondary lymphocytic invasion into the gland
parenchyma, and to parotid masses caused by Kaposi's sarcoma, Non-Hodgkin's lymphoma,
benin lymphoepithelial cysts, or else to the usual parotid neoplasms. Of note,
lymphoepithelial cysts are common in the HIV/AIDS population and are usually bilateral
and located in the tail of the parotid gland. Treatment may be difficult as they
often recur despite surgical excision or aspiration. Sclerosis with a variety
of agents, such as tetracycline, has shown some success.
Caused by a paromyxovirus, this viral
infection has become less of a medical issue with the advent of vaccination programs.
It is, however, a highly contagious infection manifest by coryza, conjunctivitis,
and a generalized cutaneous erythematous rash. In the head and neck areas, early
in the infection, small, spotty, exanthematous lesions are noted on the buccal
mucosa, referred to as Koplick's spots. In addition to producing a pharyngotonsillitis
in the course of the disease, it was a cause of acquired sensorineural hearing
loss in children, accounting for approximately 3-10% of acquired causes.(44) Although
only .1% of children with measles actually develop hearing loss along the course
of the disease, it is typically bilateral, profound in 45%, and mild to moderate
for the remainder.
Herpes Simplex Virus
Primary herpes simplex virus infection
occurs in young children, typically between the ages of 10 months and 3 years.
Transmitted by mucus or saliva, the incubation time lasts from 2-12 days after
which the child develops a system illness characterized by malaise, fever, and
pharyngitis. Examination of the pharynx reveals vesicular lesions covered with
a black crust with possible accompanying shallow tonsillar ulcers with gray exudate.
In the immunocompromised child, a disseminated form of primary HSV may occur with
resulting meningioencephalitis. Following the primary infection, the HSV resides
latent in the sensory ganglion innervating the oral cavity or oral pharyngeal
sites originally affected. Recurrence at later stages results in a limited gingivostomatitis,
with characteristic multiple punched ulcers.
Epstein-Barr virus is implicated in
80-95% of the cases of mononucleosis; however, other viruses such as cytomegalovirus,
human immunodeficiency virus, adenovirus, rubella, and hepatitis A may also produce
a mononucleosis like syndrome. It is manifest as a systemic prodromal phase of
2-5 days of malaise and fatigue followed by an exudative pharyngotonsillitis,
cervical lymphadenopathy (typically posterior), and hepatomegaly (10%), and splenomegaly
(50%). The hepatosplenomegaly is usually manifest at the 2-4th week of the illness,
where splenic rupture is a potentially serious complication of the disease. Laboratory
evidence of lymphocytosis with many atypical cells are commonly seen as well as
easy detection on commercially available Mono-spot test (heterophil positive).
Therapy is strictly supportive.
Due to more widespread vaccination
programs, this viral illness is not a common entity. It is the most common viral
disorder involving the salivary gland and was considered to be the most common
cause of parotid gland swelling. Generally affecting children 4-6 years of age,
it present with systemic complaints of fever, malaise, myalgias, and headache.
Following an incubation time of 2-3 weeks, there is pain and swelling of one or
both parotid glands. This is a self-limited infection and relies on supportive
treatment. Major complications may occur, however, consisting of pancreatitis,
orchitis, meningitis, and sudden deafness. While the hearing loss only affects
5 of 10,000 patients with measles, it tends to be unilateral in 80% of the cases
with more pronounced hearing loss at the higher frequencies.(45) Unfortunately,
the hearing loss is typically permanent.
1. Harrison's Principles of Internal
Medicine. Twelfth Edition. McGraw-Hill. 199I pg. 1437.
2. Brooker, DS. Rheumatoid Arthritis
: Otorhinolaryngological Manifestations. Otolaryngologic Clinics of North America,
3. Paparella, MM., et al. Otolaryngology.
Third Edition. WB Saunders. 1991. pg. 810.
4. Bailey, BJ., et al. Head and
Neck Surgery-Otolaryngology. J.P. Lippincott. 1993. pg. 168.
5. Cummings, CW., et al. Otolaryngology-Head
and Neck Surgery. Second Edition. Mosby Year Book. 1993. pg. 755.
6. Ibid. pg. 2300.
7. Kelly, WN. Textbook of Rheumatology.
Second Edition. WB Saunders. 1985.
8. Bailey, BJ., et al. Head and
Neck Surgery-Otolaryngology. J.P. Lippincott. 1993. pg. 157.
11. Paparella, MM., et al. Otolaryngology.
Third Edition. WB Saunders. 1991. pg. 810.
12. Bailey, BJ., et al. Head and
Neck Surgery-Otolaryngology. J.P. Lippincott. 1993. pg. 168.
14. Ataman, M., et al. Wegener's
Granulomatosis: Case Report and Review of the Literature. Rhinology. Volume
15. Kornblut, AD. Symposium of
Granulomatous Disorders of the Head and Neck. The Otolaryngologic Clinics of
North America. Vol 15 Number 3. WB Saunders.
17. Bailey, BJ., et al. Head and
Neck Surgery-Otolaryngology. J.P. Lippincott. 1993. pg. 169.
18. Cummings, CW., et al. Otolaryngology-Head
and Neck Surgery. Second Edition. Mosby Year Book. 1993. pg. 755.
19. Ibid, pg. 717.
20. Ibid, pg. 1178.
21. Ibid, pg. 2915.
22. Marion, J. Diagnosis and Treatment
of Lymphomas. In: Comprehensive Management of Head and Neck Tumors. WB Saunders.
1987., pg. 1849.
23. Ibid, pg. 1829.
24. Cummings, CW., et al. Otolaryngology-Head
and Neck Surgery. Second Edition. Mosby Year Book. 1993. pg. 1223.
25. Harrison's Principles of Internal
Medicine. Twelfth Edition. McGraw - Hill. 199I pg. 1703.
26. Bailey, BJ., et al. Head and
Neck Surgery-Otolaryngology. J.P. Lippincott. 1993. pg. 1550.
27. Ibid, pg. 101.
30. Harrison's Principles of Internal
Medicine. Twelfth Edition. McGraw-Hill. 1991 pg. 2103.
32. Paparella, MM., et al. Otolaryngology.
Third Edition. WB Saunders. 1991. pg. 814.
34. Harrison's Principles of Internal
Medicine. Twelfth Edition. McGraw - Hill. 199I pg. 437.
37. Bailey, BJ., et al. Head and
Neck Surgery-Otolaryngology. J.P. Lippincott. 1993. pg. 180.
38. Harrison's Principles of Internal
Medicine. Twelfth Edition. McGraw - Hill. 199I pg. 668.
39. Bailey, BJ., et al. Head and
Neck Surgery-Otolaryngology. J.P. Lippincott. 1993. pg. 181- 182.
40. Cummings, CW., et al. Otolaryngology-Head
and Neck Surgery. Second Edition. Mosby Year Book. 1993. pg. 2329.
41. Bailey, BJ., et al. Head and
Neck Surgery-Otolaryngology. J.P. Lippincott. 1993. pg. 776.
42. Ibid, pg. 103.
43. Ibid, pg 778.
44. Ibid, pg 1748.