Sjögren's syndrome

Sjögren's Syndrome

 

Definition

Sjögren's syndrome (SS) is a disorder in which the mouth and eyes become extremely dry. Sjögren's syndrome is often associated with other autoimmune disorders. It is named for Henrik Sjögren, a Swedish ophthalmologist.

Description

Like other autoimmune disorders, Sjögren's syndrome occurs when the body's immune system mistakenly begins treating parts of the body as foreign invaders. While the immune cells should attack and kill invaders like bacteria, viruses, and fungi, these cells should not attack the body itself. In autoimmune disorders, however, cells called antibodies see tissues of the body as foreign, and help to start a chain of events that results in damage and destruction of those tissues.

There are three types of Sjögren's syndrome. Primary Sjögren's syndrome occurs by itself, with no other associated disorders. Secondary Sjögren's syndrome occurs along with other autoimmune disorders, like systemic lupus erythematosus, rheumatoid arthritis, scleroderma, vasculitis, or polymyositis. When the disorder is limited to involvement of the eyes, with no other organ or tissue involvement evident, it is called sicca complex.

Women are about nine times more likely to suffer from Sjögren's syndrome than are men. SS affects all age groups, although most patients are diagnosed when they are between 40 and 55 years old. Sjögren's syndrome is commonly associated with other autoimmune disorders. In fact, 30% of patients with certain autoimmune disorders will also have Sjögren's syndrome.

SS is found in all races and ethnic groups. It is thought to affect between 0.1% and 3% of the population in the United States; this range reflects the lack of a uniform set of diagnostic criteria. According to the American College of Rheumatology, between 1 million and 4 million Americans have Sjögren's syndrome.

Causes and symptoms

The cause of Sjögren's syndrome has not been clearly defined, but several causes are suspected. The syndrome sometimes runs in families. Other potential causes include hormonal factors (since there are more women than men with the disease) and viral factors. The viral theory suggests that the immune system is activated in response to a viral invader, but then fails to turn itself off. Some other immune malfunction then causes the overly active immune system to begin attacking the body's own tissues. In 2004 a group of Greek researchers presented evidence that a coxsackievirus may be the disease organism that triggers SS.

The main problem in Sjögren's syndrome is dryness. The salivary glands are often attacked and slowly destroyed, leaving the mouth extremely dry and sticky. Swallowing and talking become difficult. Normally, the saliva washes the teeth clean. Saliva cannot perform this function in Sjögren's syndrome, so the teeth develop many cavities and decay quickly. The parotid glands produce the majority of the mouth's saliva. They are located lying over the jaw bones behind the area of the cheeks and in front of the ears, and may become significantly enlarged in Sjögren's syndrome.

The eyes also become extremely dry as the tear glands (called glands of lacrimation) are slowly destroyed. Eye symptoms include itching, burning, redness, increased sensitivity to light, and thick secretions gathering at the eye corners closest to the nose. The cornea may have small irritated pits in its surface (ulcerations).

Destruction of glands in other areas of the body may cause a variety of symptoms. In the nose, dryness may result in nosebleeds. In the rest of the respiratory tract, the rates of ear infection, hoarseness, bronchitis, and pneumonia may increase. Vaginal dryness can be quite uncomfortable. Rarely, the pancreas may slow production of enzymes important for digestion. The kidney may malfunction. About 33% of all patients with Sjögren's syndrome have other symptoms unrelated to gland destruction. These symptoms include fatigue, decreased energy, fevers, muscle aches and pains, and joint pain.

Many patients with SS also develop a variety of skin problems that include dry patches, vasculitis, and cutaneous B-cell lymphoma. These and other dermatologic disorders are more common in SS than was previously thought.

Patients who also have other autoimmune diseases will suffer from the symptoms specific to those conditions.

In addition to physical symptoms, patients with SS appear to be at increased risk for depression and other mood disorders.

Diagnosis

Diagnosis of Sjögren's syndrome is based on the patient having at least three consecutive months of bothersome eye and/or mouth dryness. A variety of tests can then be done to determine the quantity of tears produced, the quantity of saliva produced, and the presence or absence of antibodies that could be involved in the destruction of glands.

Treatment

There is no cure for Sjögren's syndrome. Instead, treatment usually attempts to reduce the discomfort and complications associated with dryness of the eyes and mouth (and other areas). Artificial tears are available, and may need to be used up to every 30 minutes. By using these types of products, the patient is more comfortable and avoids the complications associated with eyes that are overly dry. Dry mouth is treated by sipping fluids slowly but constantly throughout the day. Sugarless chewing gum can also be helpful. An artificial saliva is available for use as a mouthwash. Patients may also be given such drugs as pilocarpine (Salagen) or cevimeline (Evoxac) to increase saliva and tear secretions. Careful dental hygiene is important in order to avoid tooth decay, and it is wise for patients to decrease sugar intake. Vaginal dryness can be treated with certain gel preparations. Steroid medications may be required when other symptoms of autoimmune disorders complicate Sjögren's syndrome. However, these medications should be avoided when possible because they may make the cornea thin and even more susceptible to injury.

Key terms

Autoimmune disorder — A disorder in which the body's immune cells mistake the body's own tissues as foreign invaders; the immune cells then work to destroy tissues in the body.

Cornea — A transparent structure of the eye over the iris and pupil; light must pass through the cornea to make vision possible.

Coxsackievirus — Any of a group of enteroviruses that produce a disease in humans characterized by fever and rash. Coxsackieviruses are named for the town in upstate New York where they were first identified.

Immune system — The complex network of organs and blood cells that protect the body from foreign invaders, like bacteria, viruses, and fungi.

Prognosis

The prognosis for patients with primary Sjögren's syndrome is particularly good; these patients have a normal life expectancy. Although the condition is quite annoying, serious complications rarely occur. The prognosis for patients with secondary Sjögren's syndrome varies since it depends on the prognosis for the accompanying autoimmune disorder.

Prevention

Since the cause of Sjögren's syndrome is unknown as of 2004, there are no known ways to prevent this syndrome.

Resources

Books

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Diffuse Connective Tissue Disease." Section 5, Chapter 50 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Moutsopoulos, Haralampos M. "Sjögren's Syndrome." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1997.

Periodicals

Bell, Mary, et al. "Sjögren's Syndrome: A Critical Review of Clinical Management." The Journal of Rheumatology 26, no. 9 (2001): 2051-2059.

Francis, Mark L., MD. "Sjogren Syndrome." eMedicine July 1, 2004. http://emedicine.com/med/topic2136.htm.

Ono, M., E. Takamura, K. Shinozaki, et al. "Therapeutic Effect of Cevimeline on Dry Eye in Patients with Sjögren's Syndrome: A Randomized, Double-Blind Clinical Study." American Journal of Ophthalmology 138 (July 2004): 6-17.

Roguedas, A. M., L. Misery, B. Sassolas, et al. "Cutaneous Manifestations of Primary Sjögren's Syndrome Are Underestimated." Clinical and Experimental Rheumatology 22 (September-October 2004): 632-636.

Stevenson, H. A., M. E. Jones, J. L. Rostron, et al. "UK Patients with Primary Sjögren's Syndrome Are at Increased Risk from Clinical Depression." Gerodontology 21 (September 2004): 141-145.

Triantafyllopoulou, A., N. Tapinos, and H. M. Moutsopoulos. "Evidence for Coxsackievirus Infection in Primary Sjögren's Syndrome." Arthritis and Rheumatism 50 (September 2004): 2897-2902.

Organizations

American College of Rheumatology. 1800 Century Place, Suite 250, Atlanta, GA 30345-4300. (404) 633-3777. Fax: (404) 633-1870. http://www.rheumatology.org.

Sjögren's Syndrome Foundation, Inc. 8120 Woodmont Avenue, Bethesda, MD 20814. (800) 475-6473. Fax: (301) 718-0322. http://www.sjogrens.org.

Other

American College of Rheumatology Fact Sheet. "Sjögren's Syndrome." http://www.rheumatology.org/public/factsheets/sjogrens_new.asp?aud=pat.

Sjögren's syndrome

 [sha´grenz]

a symptom complex of unknown etiology, usually occurring in middle-aged or older women, marked by the triad of keratoconjunctivitis sicca with or without lacrimal gland enlargement, xerostomia with or without salivary gland enlargement, and the presence of a connective tissue disease, usually rheumatoid arthritis but sometimes systemic lupus erythematosus, scleroderma, or polymyositis. An abnormal immune response has been implicated. The dryness and the discomfort related to the lack of secretions are treated symptomatically.

Sjögren's syndrome

(shō′grənz, shœ′-) also

Sjögren syndrome

(-grĕn)

n.

A chronic autoimmune disease occurring mostly in older women, characterized by keratoconjunctivitis, dryness of mucous membranes, joint pain, fatigue, and enlargement of the parotid glands. It is often associated with rheumatoid arthritis, Raynaud's phenomenon, and dental caries.

Sjögren's syndrome

Etymology: Henrik S.C. Sjögren, Swedish ophthalmologist, 1899-1986

an immunological disorder characterized by deficient fluid production by the lacrimal, salivary, and other glands, resulting in abnormal dryness of the mouth, eyes, and other mucous membranes. The symptoms primarily affect women over 40 years of age. Atrophy of the lacrimal glands can lead to desiccation of the cornea and conjunctiva with damage to the tissues. Atrophy of the salivary glands results in dental disorders and loss of taste and odor sensations. When the lungs are affected, the dryness increases susceptibility to pneumonia and other respiratory infections. Sjögren's syndrome is frequently associated with Raynaud's phenomenon, rheumatoid arthritis, Waldenström's macroglobulinemia, and lymphoma. Treatment includes applying artificial tears and using soft contact lenses that can be moistened often, sipping fluids frequently to prevent mouth dryness, and avoiding medications that tend to deplete body fluids. See also dry eye syndrome, keratoconjunctivitis sicca.

Sjögren's syndrome

An immunological disorder causing reduced secretion of many exocrine glands as a result of damage by antibodies produced by the body (autoantibodies). Affected glands are infiltrated with lymphocytes. Their malfunction causes severe dryness of the eyes, mouth and vagina. The syndrome is commonly associated with other immunological disorders, such as RHEUMATOID ARTHRITIS, SYSTEMIC LUPUS ERYTHEMATOSUS and MYASTHENIA GRAVIS. Treatment is by anti-inflammatory and cytotoxic drugs and symptomatic relief can be obtained from artificial tears, moistening mouth sprays and vaginal lubricants. (Henrik Samuel Conrad Sjögren, b. 1899, Swedish ophthalmologist).

Sjögren’s Syndrome

DRG Category:	546
Mean LOS:	5.2 days
Description:	MEDICAL: Connective Tissue Disorders With CC

Sjögren’s syndrome (SS) is the most common autoimmune rheumatic disorder after rheumatoid arthritis (RA). It is a chronic, progressive disease associated with other diseases, such as RA, in approximately 50% of the cases.

SS is characterized by failure of exocrine glands and by diminished tearing and salivary secretion (sicca complex). It results from chronic exocrine gland dysfunction, although the disorder may also involve other organs such as the lung and kidney. SS may be a primary disorder or it may be associated with connective tissue disorders, such as RA, scleroderma, systemic lupus erythematosus, and primary biliary cirrhosis. Tissue damage results either from infiltration by lymphocytes or from the deposition of immune complexes. The overall prognosis for patients with SS is good, and the disease seldom leads to significant complications.

Causes

The direct cause of SS is unknown. It seems likely that both environmental and genetic factors (see Genetic Considerations) contribute to its development. In a genetically susceptible individual, either bacterial or viral infection or exposure to pollen may be the catalyst for SS.

Genetic considerations

SS is believed to be a complex disorder with a genetic susceptibility and an environmental trigger. Associations with the human leukocyte antigen variants DRB1, DRB1∗03, and DQB1∗02 have been described.

Gender, ethnic/racial, and life span considerations

SS occurs mainly in women: 9 out of 10 patients are female. The mean age of occurrence is 50, although it has been reported in children who develop parotid gland enlargement. A small percentage of women who develop SS may have accompanying nonlymphoma and lymphoid malignancies. No racial and ethnic considerations are known.

Global health considerations

SS occurs around the globe with similar prevalence as found in North America.

Assessment

History

Establish a history of either autoimmune or lymphoproliferative disorders. Rule out other causes of oral and ocular dryness; ask about any history of sarcoidosis, endocrine disorders, anxiety or depression, and radiation therapy to the head and neck. Many commonly used medications produce dry mouth as a side effect, so take a thorough history of medications. In patients with salivary gland enlargement and severe lymphoid infiltration, rule out malignancy. Approximately 50% of patients with SS have confirmed RA. When you ask about symptoms, the patient may report gritty or sandy sensations in the eye or a film across the visual field. Patients may also report dryness of the mouth, burning oral discomfort, difficulty in chewing and swallowing dry foods, increased thirst, and reduced taste. The patient may also report the incidence of many dental caries and chronic middle ear infections. Dryness of the vagina and vulva leads to reports of painful urination, itching, and painful or difficult sexual intercourse.

Physical examination

The most common symptoms are dry eyes and dry mouth. The patient’s tongue is often red and dry with atrophic taste buds. Unilateral or bilateral parotid and salivary glands may be hardened and nontender. Dental caries are a common finding. The dryness may make talking difficult. Patients may have a dry, chronic cough and an increased incidence of upper and lower respiratory tract infections, which has resulted in a chronic vocal hoarseness. Nasal mucosa may be dry and reddened. Gastrointestinal tract involvement may lead to gastritis, esophageal mucosal atrophy, and difficulty in swallowing. Genitalia may appear dry and possibly ulcerated. Involvement of the exocrine glands leads to dry, tough, scaly skin; decreased sweat; and chronic itching.

Psychosocial

The patient with SS has complaints that may have been attributed to multiple causes, possibly over years. Because SS is closely related to systemic lupus erythematosus and RA, the patient may have been misdiagnosed, causing considerable emotional distress. Because SS affects senses, such as sight and taste, and also sexuality, assess the patient’s ability to cope with the presenting symptoms and other common complaints.

Diagnostic highlights

Test	Normal Result	Abnormality With Condition	Explanation
Salivary gland biopsy	Normal salivary gland cells	Presence of inflammatory cells and immune complexes	Identifies abnormal cells in secretory glands and ducts
Slit-lamp examination	Normal examination	Detection of dryness of conjunctiva and reduced tearing	Identifies reduced tear film and dryness of eyes

Other Tests: Complete blood count, antinuclear antibodies, rheumatoid factor, anti-alpha-fodrin antibody, erythrocyte sedimentation rate, tear osmolarity, fluorescence clearance test, parotid flow rate, radionuclide scan, Schirmer test (test strip of number 41 Whatman filter paper placed near the lower conjunctival sac to measure tear formation; healthy persons wet 15 mm or more after 5 minutes)

Primary nursing diagnosis

Diagnosis

Impaired skin integrity related to diminished or absent glandular secretions

Outcomes

Tissue integrity: Skin and mucous membranes; Wound healing: Primary intention; Knowledge: Treatment regimen; Self-care: Hygiene; Treatment behavior: Illness

Interventions

Skin and membrane surveillance; Skin care; Medication administration; Fluid balance; Surveillance

Planning and implementation

Collaborative

Care of the patient with SS is designed to treat symptoms. Instill artificial tears as often as every 30 minutes to prevent corneal ulcerations or opacifications that may be caused by insufficient lacrimal secretions.

Patients who also have RA may benefit from a combined program of medical, rehabilitative, and surgical treatments. The primary goals are suppression of further joint and tissue inflammation, maintenance of joint and tissue function, repair of joint damage, and relief of pain.

Pharmacologic highlights

Medication or Drug Class	Dosage	Description	Rationale
Cyclosporine ophthalmic eye drops	Apply 1% or 2% solution bid	Immunosuppressant	Suppresses T-cell formation and has been used to increase lacrimal gland function in SS

Other Drugs: Corticosteroids; eye lubricants; omega-3 fish oil; sustained-release cellulose capsules (hydroxypropyl cellulose) may be used. Topical (diquafosol) and systematic (pilocarpine, cevimeline) stimulators of tear secretion may be used. If eye infection develops, the patient receives antibiotics; topical steroids are avoided.

Independent

Suggest the use of sunglasses to protect the patient’s eyes from strong light, wind, and dust. To reduce the risk of infection caused by dry eyes, advise the patient to keep his or her face clean and to avoid rubbing the eyes. Mouth dryness can be relieved by using a swab or spray and by drinking plenty of fluids, especially at mealtime. Sugarless throat lozenges can also relieve mouth dryness without promoting tooth decay. Meticulous oral hygiene should include regular brushing, flossing, and fluoride treatment at home, along with frequent dental checkups. Teach the patient to avoid medications that decrease saliva production, such as atropine derivatives, antihistamines, anticholinergics, and antidepressants. Suggest high-protein, high-calorie liquid supplements to patients with painful mouth lesions. Soft foods may be easier for patients to swallow. Parotid gland enlargement can be treated with local heat and analgesia.

Respiratory dryness can be reduced by using a humidifier at home and at work. Nasal dryness can be relieved by the use of normal saline solution drops. Moisturizing lotions can ease skin dryness, as can avoiding lengthy hot showers or baths. Patients should avoid sunburn and any lengthy exposure to the sun; recommend using a sunscreen when outdoors. Water-soluble lubricating jelly is an effective lubricant during sexual intercourse.

Evidence-Based Practice and Health Policy

Segal, B.M., Pogatchnik, B., Holker, E., Liu, H., Sloan, J., Rhodus, N., & Moser, K.L. (2013). Primary Sjogren’s syndrome: Cognitive symptoms, mood, and cognitive performance. Acta Neurologica Scandinavica, 125(4), 272–278.

• In a study comparing 39 adult patients with primary SS to 17 healthy control participants, 47% of SS patients reported depression compared to 6% of control participants.
• Depression was significantly correlated with cognitive functioning (r, 0.782; p < 0.001). Compared to control participants, patients with SS performed worse in psychomotor processing (p = 0.027) and verbal reasoning (p = 0.007).

Documentation guidelines

• Physical findings of dysphagia (difficulty swallowing)
• Physical findings of presence of red, irritated, or ulcerated mucosal membranes
• Reaction to remoisturizing eyes, mouth, and other affected areas

Discharge and home healthcare guidelines

Instruct the patient to avoid sugar; tobacco; alcohol; and spicy, salty, and highly acidic foods. Recommend high-calorie, protein-rich liquid supplements to patients with painful mouth lesions. Teach the patient how to instill eye drops, ointments, or sustained-release capsules. Advise the patient to avoid over-the-counter medications that include saliva-decreasing compounds, such as antihistamines, antidepressants, anticholinergics, and atropine derivatives.

syndrome

aggregated objective signs, subjective symptoms and specific pathologies that typify specific conditions

• acquired immunodeficiency syndrome; AIDS severe reduction in numbers of T4 lymphocyte helper (CD4) cells (due to infection with human immunodeficiency virus [HIV]) and resultant compromise of humoral and cell-mediated immunity; patients show lymphadenopathy, opportunistic infections (e.g. tinea and verrucae) and unusual infections (e.g. histoplasmosis, gastrointestinal tract candidiasis, Pneumocystis carnii pneumonia [PCP]), unusual malignancies (e.g. Kaposi's sarcoma), wasting diseases and presenile dementia

• acute compartment syndrome; ACS increased lower-limb intracompartmental pressure on exercise (exercise expands muscles, increases intracompartmental pressures, inducing pain); treated initially by rest, immobilization, non-steroidal anti-inflammatory drugs; severe cases may require surgical decompression (fasciotomy)

• anterior tarsal syndrome; ATS deep peroneal nerve entrapment at anterior ankle/dorsal talonavicular joint, due to restriction of ankle dorsiflexion (e.g. tight boots; ski boots), or local soft-tissue trauma (e.g. dorsal tarsal exostoses); characterized by extensor hallucis longus weakness, dorsal foot paraesthesia and numbness of first intermetatarsal space (symptoms can be induced by deep peroneal nerve percussion as crosses the anterior aspect of the ankle joint, or by ankle joint plantarflexion whilst simultaneously dorsiflexing toes)

• anterior tibial compartment syndrome ischaemic necrosis of anterior compartment muscle fibres, due to local arterial compression by engorged muscles, after unaccustomed exertion

• anterior tibiotalar impingement syndrome anterior ankle pain at ankle dorsiflexion (e.g. at midstance, just before heel lift) due to inferior tibial/neck of talus exostosis

• Apert's syndrome type Ia acrocephalosyndactyly, characterized by features of Carpenter's syndrome, with lesser digital (2-5) fusion into one mass, usually with a common mega-nail

• Apert-Crouzon syndrome type IIa acrocephalosyndactyly characterized by features of Carpenter's syndrome with additional craniofacial dysostosis, maxillary hypoplasia, and 2-4 digit fusion

• Bazex syndrome; acrokeratosis paraneoplastica keratoderma (i.e. erythema, scaling and irritation) of skin of ears, nose, hands and feet and later generalized hyperkeratosis in men with underlying internal malignancy; condition regresses when underlying malignancy is resolved

• Behçet's syndrome chronic vasculitic disease of unknown cause; characterized by seronegative arthritis of knees and ankles, elbows and wrists, mouth ulcers, erythema nodosum, visual impairment and cerebrovascular accident

• benign familial joint hypermobility syndrome; BFJHS generalized joint hypermobility, diagnosed as 2 major/1 major + 2 minor/4 minor criteria (see Table 1) in the absence of Ehlers-Danlos syndrome, Marfan's syndrome and osteogenesis imperfecta

• Brocq-Lyell syndrome; toxic epidermal necrolysis severe, acute, systemic drug reaction characterized by hyperpigmented skin lesions and epidermal detachment

• Brown-Séquard syndrome hemiparaplegia and hyperaesthesia, with ipsilateral loss of stereognosis and contralateral hemianaesthesia; due to unilateral spinal cord lesion

• carpal tunnel syndrome pain, paraesthesia and loss of power of palmar muscles; associated with rheumatoid arthritis

• Carpenter's syndrome; acrocephalopolysyndactyly oxycephaly, bradysyndactyly and polydactyly of the feet, with learning difficulties

• Charcot's syndrome see intermittent claudication

• chronic compartment syndrome; CCS; chronic exertional compartment syndrome exercise-induced fascial compartment pain; caused by compromised circulation and relative ischaemia of intracompartmental tissues, with long-term muscle and nerve dysfunction and damage; recalcitrant cases require surgical decompression through fasciotomy (see syndrome, acute compartment)

• compartment syndrome see syndrome, acute compartment; syndrome, chronic compartment

• complex regional pain syndrome; CRPS; chronic regional pain syndrome neuroinflammatory dysfunction, due to ion interaction of nociceptive C-fibre nerve endings, the sympathetic nervous system and spinal cord efferent motor nerves; characterized by vasomotor instability, hyperalgesia and impaired motor function; diagnosed from clinical presentation, symptoms reduction on administration of sympathetic nerve blockade, and intense, focal periarticular uptake of contrast medium in a delayed imaging-phase bone scan; treated by early, aggressive physical therapy to prevent contracture and muscle wasting, symptomatic relief by sympathetic nerve blockade, non-steroidal anti-inflammatory drugs, tricyclic antidepressants and anticonvulsant medication; immobilization is contraindicated

• complex regional pain syndrome type 1; CRPS 1; reflex sympathetic dystrophy; Sudek's atrophy; allodynia sympathetic nervous system-mediated acute pain and vasomotor instability, triggered by minor or surgical trauma without obvious nerve injury; affects women more than men; pain is excessive and out of proportion to severity of initiating injury; diagnosis is based on clinical symptoms aided by bone scan, laser Doppler studies and thermography; patients may show anxiety, depression and disturbed sleep; condition is difficult to manage; patients suspected of CRPS 1 should have early referral to a pain clinic (see Table 2); presents in three stages:

  • stage 1 acute phase, lasting 2-3 months, with regional severe burning pain, warmth and swelling triggered by stress/light touch, bone demineralization, skin trophic changes

  • stage 2 dystrophic phase/Sudek's atrophy; lasting for several months; characterized by constant unrelenting pain, exacerbated by any stimulus, and tissue cyanosis, coolness and induration, and diffuse osteoporosis

  • stage 3 atrophic phase, characterized by reduced/absent/intractable pain, irreversible atrophy of skin/subcutaneous tissues, flexion contractures of foot, advanced osteoporosis with a 'ground-glass' appearance on X-ray of affected bone

• complex regional pain syndrome, type 2; CRPS 2; causalgia; sympathetic pain syndrome persistent and severe skin paraesthesia/burning sensations; caused by trauma to peripheral sensory nerve fibres; symptoms, progress and treatment are similar to that of CRPS 1

• Conn's syndrome primary aldosteronism; characterized by headaches, thirst, nocturia, polyuria, hypovolaemia, fatigue, hypertension, alkalosis, and potassium depletion

• constrictive band syndrome intrauterine development of deep, tight, circumferential folds around leg/foot, and compromised limb development distal to band (e.g. autoamputation; marked oedema of distal tissues); thought to relate to strands of amniotic membrane enwrapping the developing limb

• Cushing's syndrome raised blood cortisol (e.g. due to pituitary tumour; long-term steroid therapy); characterized by central obesity, moon-like facies, acne, skin striae, hypertension, decreased carbohydrate tolerance and tendency to diabetes, female amenorrhoea and hirsutism

• Down's syndrome chromosomal disorder (trisomy 21) characterized by congenital short stature, broad short hands/feet, characteristic facies (pronounced epicanthic skin folds, flat hypoplastic face, short nose, enlarged tongue), transverse palmar crease, very dry skin, learning difficulties; formerly termed mongolism

  Edwards' syndrome trisomy 18, with congenital characteristic facies (micrognathia, low-set ears), rocker-bottom feet, severe learning difficulties; affected children often die in early childhood

• Ehlers-Danlos syndrome; Ehlers-Danlos diseases I-X hereditary connective tissue disorder characterized by collagen abnormality, marked generalized skin and blood vessel laxity, and joint hypermobility; skin is readily traumatized and heals slowly; see syndrome, hypermobility

• Franconi's syndrome a form of anaemia associated with renal tubule dysfunction; adult Franconi's syndrome shows synostosis with osteomalacia, and acquired Franconi's syndrome is associated with multiple myeloma

• Giles de la Tourette syndrome motor incoordination characterized by verbal, facial or limbic tics

• Gorlin's syndrome multiple naevus-like basal cell carcinomata, causing small pits and depressions of palmar and plantar skin

• Guillain-Barré syndrome; acute inflammatory polyneuropathy; acute idiopathic polyneuritis; infectious polyneuritis; postinfective polyneuropathy sudden-onset, acute, postviral polyneuritis; presents as distal pain, muscular weakness/flaccidity, paraesthesia; spreads proximally over 14-21 days; severe cases show spinal nerve involvement, with respiratory failure and limb paralysis (patient will require life support and anticoagulation to prevent deep-vein thrombosis); spontaneous recovery occurs over several weeks/months; some residual neuromotor effects may persist

• Haglund's syndrome prominence of posterior superior lateral area of calcaneum, retrocalcaneal bursitis, Achilles tendon thickening and Achilles tendinitis; diagnostic rearfoot radiographic features include positive parallel pitch lines, loss of retrocalcaneal recess (indicating retrocalcaneal bursitis), Achilles tendon thickening, loss of distinct interface between Achilles tendon and pre-Achilles fat pad

• heel pain syndrome see heel pain

• heel spur syndrome see heel spur

• Howel-Evans syndrome familial palmoplantar keratoderma, with increased risk of oesophageal cancer

• Hurler's syndrome; lipochondrodystrophy; dysostosis multiplex autosomal-recessive inherited generalized lipid disturbance and mucopolysaccharoidosis, affecting cartilage, bone, skin, subcutaneous tissues, brain, liver and spleen; characterized by short stature, shortness of neck, trunk and digits, kyphosis, reduced joint mobility, learning difficulties, characteristic facies (so-called gargoylism) and visual impairment

• hypermobility syndrome; joint hypermobility syndrome disordered collagen (types 1 and 3) structure, with associated decreased tensile strength of skin/structural tissues; characterized by generalized joint hypermobility, easy bruising, impaired healing, increasing incidence of joint/soft-tissue pain, joint dislocation and osteoarthritis; a presenting feature of benign familial joint hypermobility syndrome (BFJHS) (see Table 3), Ehlers-Danlos syndrome, Marfan syndrome and osteogenesis imperfecta

• iliotibial band syndrome; ITBS; iliotibial band friction syndrome; ITBFS overuse-associated, friction-induced inflammation of ITB and associated bursa, where ITB moves over lateral femoral condyle (Gerdy's tubercle); due to repeated knee flexion and extension, especially in athletes/cyclists; presents as ITB pain at heel strike progressing to constant ITB pain; early-stage treatment includes a daily stretching programme (see Table 4) and application of heat (pre-exercise) and ice (postexercise) (see Table 5)

• joint hypermobility syndrome see syndrome, hypermobility

• lobster-claw syndrome extreme form of ectrodactyly; characterized by absence of third and fourth rays

• Korsakoff's syndrome confusion and severe memory impairment with confabulation and Wernicke's syndrome, associated with chronic alcoholism

• Lyell's syndrome drug-induced, acute skin sensitivity reaction; characterized by acute erythema, urticaria, vasculitis, purpura, marked exfoliation (peeling), flaccid bullae formation, subepidermal separation/detachment

• Marfan's syndrome familial, autosomal-dominant, congenital changes in mesodermal and ectodermal tissues; characterized variably by musculoskeletal changes (e.g. increased height, excessive limb length, arachnodactyly; generalized tissue laxity and joint hypermobility), visual effects, and cardiovascular effects (e.g. aortic aneurysm)

• medial tibial stress syndrome; MTSS; tibial fasciitis; shin splint muscle fatigue, reduced shock absorption, traction enthesiopathy and periostitis along anterior and posterior medial lower one-third of tibia (see Table 6) secondary to overuse/underpreparation for exercise; exacerbated by exercising on hard surfaces, especially in individuals who pronate excessively; treated by muscle-strengthening exercises, pre-exercise flexibility programme, modification of overall sports exercise programme (see Table 7), in conjunction with gait analysis, orthoses and correct shoe selection

• Morquio's syndrome; type IV mucopolysaccharoidosis severe skeletal dysplasia including spine/thorax deformity, irregular epiphyses but normal shaft length of long bones, enlarged joints, flaccid ligaments, waddling gait and urinary abnormalities, due to autosomal-recessive error of mucopolysaccharide metabolism

• Morton's syndrome congenital shortening of first metatarsal with apparent shortening of hallux and associated metatarsalgia

• Munchausen's syndrome repeated fabrication of illness/symptoms of illness

• Munchausen's syndrome by proxy repeated reporting of spurious illness/symptoms of illness by one person about another

• musculoskeletal pain syndrome see polymyalgia rheumatica

• nail-patella syndrome; hereditary arthrodysplasia autosomal-dominant abnormality of finger/toenails, absent/hypoplastic patella, defects of head of radius and iliac horns, and iris discoloration

• nephrotic syndrome peripheral oedema, albuminuria, reduced plasma albumin (hypoalbuminaemia), refractory bodies in urine and raised blood cholesterol

• nerve entrapment syndromes local nerve trunk compression (e.g. tibial, medial calcaneal lateral, first lateral branch of calcaneal, lateral plantar, high tibial, popliteal, deep peroneal, superficial, saphenous, sural or medial common hallucal nerves), as in tarsal/carpal tunnel syndromes, plantar digital neuritis, Morton's neuroma; characterized by distressing distal dermatomal sensory (e.g. pain and paraesthesia) and/or motor symptoms (e.g. muscle atrophy) (see Table 8)

• Nievergelt-Pearlman syndrome rare autosomal-dominant bone disease causing lower-limb 'rhomboidal' tibia/fibula (crura rhomboidei), joint dysplasias, genu valgum, club foot, deformed toes; more common in males

• overlap syndromes see mixed connective tissue diseases

• patellofemoral joint syndrome see syndrome, runner's-knee

• peroneal cuboid syndrome loss of rearfoot eversion due to long-standing peroneal tendon dysfunction/tendinitis; characterized by plantar pain from cuboid to first metatarsal

• polycystic ovary syndrome see syndrome, Stein-Leventhal

• Raynaud's syndrome concomitant Raynaud's disease (always affecting hands, and frequently feet) in patients with connective tissue disorders, characterized by generalized digital cyanosis, localized painful vasculitic lesions of dorsal forefoot (30% of cases) and apices of toes (20-25% of cases); subcutaneous calcinosis (20% of cases) may masquerade as a seed corn

• Reiter's syndrome urethritis, iridocyclitis, arthritis, plantar enthesiopathy and heel spur formation, often triggered by earlier gastrointestinal Escherichia coli infection or exposure to a sexually transmitted disease (e.g. Chlamydia trachomatis); more common in human leukocyte antigen (HLA) B27 tissue-type males; see keratoderma blenorrhagicum

• restless-leg syndrome overwhelming need to move the lower limbs constantly; characteristic of chronic renal failure; thought to be triggered by accumulation of metabolites and uraemia

• Reye's syndrome cerebral oedema and death (in 50% of cases, usually children), provoked by aspirin therapy; aspirin is proscribed for children less than 16 years old

• Riley-Day syndrome; familial dysautonomia autosomal-dominant complete indifference to pain; also characterized by orthostatic hypotension, hyperhidrosis and hyporeflexic/absent deep tendon reflexes, pes cavus and trophic plantar ulceration

• Roussy-Levy syndrome; hereditary areflexic dystasia; Charcot-Marie-Tooth (CMT) disease type II essential tremor, sensory ataxia, poor coordination and judgement of movement, kyphoscoliosis and distal muscle atrophy (especially peronei); autosomal-dominant inherited disease similar to CMT disease type 1, but developing in early childhood

• runner's-knee syndrome mild lateral subluxation of patella in patellar groove; due to an increase in Q angle (i.e. >15°), often in association with excessive foot pronation, tibial varum, internal tibial torsion, weakened quadriceps group, malposition of vastus medialis, hard running surfaces or faulty sports shoes, leading to uneven pressure on anterolateral surface of femoral condyle and local pain; often affects female runners; treated by prescription orthoses to reduce torque, torsion and knee joint stress

• scalded-skin syndrome scaled/peeling appearance of skin overlying areas of infection, or associated with adverse drug reactions

• 'second-class travel' syndrome pulmonary thromboembolism due to prolonged periods of inactivity, e.g. passengers (who have been static for > 4 hours during long-haul intercontinental air flights) develop deep-vein thrombosis; the clot detaches, passing through venous circulation and heart, to block the pulmonary artery; characterized by sudden collapse and death; passengers on long-haul flights are advised to undertake leg muscle exercises regularly throughout the duration of the flight, wear 'antithrombotic' elasticated hosiery and consider medication with aspirin in the weeks before long-haul flight

• sinus tarsi syndrome sensation of unsteadiness when walking on gravel/uneven ground and ongoing pain in lateral tarsal area just distal to and level with lateral malleolus, subsequent to inversion sprain/excess rearfoot pronation (e.g. as in rearfoot rheumatoid arthritis); local symptoms are exacerbated by heel inversion/eversion; treated by non-steroidal anti-inflammatory drugs, local immobilization, orthoses or steroid injection

• SjÖgren's syndrome; sicca syndrome; keratoconjunctivitis sicca oral mucous membranes dryness, loss of lacrimal secretion, facial telangiectasias (i.e. butterfly rash), bilateral parathyroiditis (in younger women), strongly associated with rheumatoid arthritis and Raynaud's phenomenon

• Stein-Leventhal syndrome; polycystic ovary syndrome multiple ovarian cyst formation, with associated menstrual abnormalities, infertility, enlarged ovaries, insulin resistance, obesity, acne, evidence of masculinization (e.g. hirsuitism) and increased tendency to type 2 diabetes mellitus; responds to treatment with oral contraceptive pill and/or metformin

• Stevens-Johnson syndrome widespread bullous erythema multiforme of skin/mucous membranes; due to hypersensitivity/drug reaction

• talar compression syndrome posterior ankle pain when foot is maximally plantarflexed at ankle joint; due to compression of posterior tubercle of talus on posterior margin of distal end of tibia; note: similar condition occurs with os trigonum, which impinges on posteroinferior margin of tibia (see Table 9)

• tarsal tunnel syndrome; TTS pain, paraesthesia and numbness in sole of foot; due to tibial nerve compression within tarsal tunnel; associated with excess foot pronation or rearfoot rheumatoid arthritis; symptoms reproduced by tapping the skin overlying distal medial malleolar area (Tinel's sign positive); conservative treatment includes valgus filler pads, cobra pads and medial heel wedges, or control of excessive rearfoot pronation with moulded cushioned orthoses worn with bespoke shoes, together with non-steroidal anti-inflammatory drugs and/or disease-modifying antirheumatic drugs; surgical treatment includes decompression procedures to free posterior tibial nerve and excise local fibrous structures (see tarsal tunnel)

• distal tarsal tunnel syndrome isolated entrapment of medial/lateral plantar nerves; medial plantar nerve is compressed between navicular tuberosity and belly of abductor hallucis longus, causing 'jogger's foot'; first branch of lateral plantar nerve (Baxter's nerve) may be entrapped as it courses laterally between bellies of abductor hallucis and quadratus plantae (flexor accessories) muscles (see Table 10)

• proximal tarsal tunnel syndrome entrapment of posterior tibial nerve/its branches deep to flexor retinaculum; due to excessive subtalar joint pronation (with narrowing of tarsal tunnel, e.g. in rheumatoid foot) due to entrapment within attachments of flexor retinaculum, compression by an enlarged abductor hallucis muscle belly, enlarged navicular tuberosity, accessory navicular, presence of os tibialis externum, ischaemic compromise of posterior tibial nerve, or varicosities within tarsal tunnel

• trisomy 21 syndrome see syndrome, Down's

• Turner's syndrome sex-chromosome (XO) abnormality affecting 1:2500 females, with characteristic morphology (web neck, short stature), infantilism and amenorrhoea, coarctation of aorta and peripheral oedema; feet are oedematous, short and broad, show excess subtalar joint pronation and hyperextended halluces; nails tend to involution, and affected subjects are prone to ingrowing nails

• Werner's syndrome autosomal-recessive condition characterized by scleroderma-like skin, cataracts, progeria (premature senility), hypogonadism and diabetes mellitus

• Wernicke's syndrome; Wernicke-Korsakoff syndrome; Wernicke's encephalopathy brainstem ischaemia causing nystagmus and other ocular effects, tremors and ataxia, mental confusion, hypothermia and hypotension; more common in chronic alcoholics

• Wolff-Parkinson-White syndrome congenital atrioventricular interconnection causing tachycardia and characteristic electrocardiogram pattern

• yellow-nail syndrome see nail, yellow

Major criteria

Current/historic Brighton score of 4/9

Arthralgia for >3/12 in four or more joints

Minor criteria

Current/historic Brighton score of 1, 2 or 3/9 (0, 1, 2, 3/9 if >50 years old)

Arthralgia for minimum of 3 months in 1-3 joints, or back pain for minimum of 3 months, or spondylosis/spondylolysis/spondylolisthesis

Dislocation/subluxation of > one joint, or one episode of simultaneous dislocation/subluxation of more than one joint

Three or more lesions of soft-tissue rheumatism (e.g. spondylitis, tenosynovitis, bursitis)

Marfanoid habitus (i.e. tall, slim physique, span:height ratio >1.3, upper:lower segment ratio <0.89, arachnodactyly [+Steinberg/wrist signs])

Abnormal skin: striae, hyperextensibility, thin skin, papyraceous scarring

Eye signs: drooping eyelids, myopia, antimongoloid slant

Varicose veins or hernia or uterine/rectal prolapse

Note: BFJHS is diagnosed in the presence of two major criteria, or one major and two minor criteria, or four minor criteria (adapted from Grahame R, Bird HA, Child A, Dolan AL, Fowler-Edwards A, Ferrell W, Gurley-Green S, Keer R, Mansi E, Murray K, Smith E. The British Society Special Interest Group on Heritable Disorders of Connective Tissue Criteria for the Benign Joint Hypermobility Syndrome. "The Revised (Brighton 1998) Criteria for the Diagnosis of the BJHS". Journal of Rheumatology 2000; 27:1777-1779).

Table 2: Features of complex regional pain syndrome

Phase	Features
Acute phase (duration: 2-3 months) Reversible	Severe burning pain, warmth, swelling and joint stiffness within a limb: not confined to a dermatome or myotome Bone demineralization Symptoms (exacerbated by limb dependence, contact or stress) persist for 2-3 months
Chronic phase (duration: several months) Reversible	Pain continues The limb becomes cool, firm and cyanotic Radiographs show diffuse osteoporosis Digits develop flexure contractures Persists for several months
Atrophic phase Irreversible	Pain diminishes or becomes intractable Skin and subcutaneous tissues become atrophic Flexion contractures in foot become fixed Osteoporosis becomes advanced; bone has a 'ground-glass' appearance

Major criteria

Current/historic Brighton score of 4/9

Arthralgia for >3/12 in four or more joints

Minor criteria

Current/historic Brighton score of 1, 2 or 3/9 (0, 1, 2, 3/9 if >50 years old)

Arthralgia for minimum of 3 months in 1-3 joints, or back pain for minimum of 3 months, or spondylosis/spondylolysis/spondylolisthesis

Dislocation/subluxation of > one joint, or one episode of simultaneous dislocation/subluxation of more than one joint

Three or more lesions of soft-tissue rheumatism (e.g. spondylitis, tenosynovitis, bursitis)

Marfanoid habitus (i.e. tall, slim physique, span:height ratio >1.3, upper:lower segment ratio <0.89, arachnodactyly [+Steinberg/wrist signs])

Abnormal skin: striae, hyperextensibility, thin skin, papyraceous scarring

Eye signs: drooping eyelids, myopia, antimongoloid slant

Varicose veins or hernia or uterine/rectal prolapse

Note: BFJHS is diagnosed in the presence of two major criteria, or one major and two minor criteria, or four minor criteria (adapted from Grahame R, Bird HA, Child A, Dolan AL, Fowler-Edwards A, Ferrell W, Gurley-Green S, Keer R, Mansi E, Murray K, Smith E. The British Society Special Interest Group on Heritable Disorders of Connective Tissue Criteria for the Benign Joint Hypermobility Syndrome. "The Revised (Brighton 1998) Criteria for the Diagnosis of the BJHS". Journal of Rheumatology 2000; 27:1777-1779).

Table 4: Iliotibial band-stretching regime

Muscle group	Action (hold for 5-10 seconds; repeat ×5, three times a day)
Hip abductor	Stand erect, legs straight, feet together; stretch trunk (on frontal plane) towards the unaffected leg
Iliotibial band	Lie on a bench on the unaffected side, with the unaffected hip and knee slightly flexed, in order to maintain balance; flex the affected hip and straighten the affected knee so that the affected leg hangs off the bench; allow the iliotibial band of the affected leg to be stretched by gravitational pull Lie on a bench on the affected side with the affected leg in line with the body and the hip and knee locked; flex the unaffected (upper) leg; place the hands on the bench immediately under the shoulder and push the trunk upwards as far as possible to apply stretch to the lateral area of the affected leg
Upper iliotibial band	Stand erect; with affected leg behind normal leg; stretch trunk (on frontal plane) towards unaffected side
Lower iliotibial band	Stand erect as above, with the knee of the affected leg slightly flexed and hips rotated (on transverse plane) towards affected leg; stretch trunk (on frontal plane) towards the unaffected side
Iliotibial band and hamstrings	Stand erect, with the affected leg behind the normal leg so that the knee of the affected leg rests on the posterior aspect of the non-affected knee; rotate the trunk (on transverse plane) away from the affected leg and attempt to touch the heel of the affected leg

Table 5: Treatment regime for iliotibial band syndrome

	Visit	Action
1	Examination Including Nobel's and Ober's tests, and excluding other causes of knee joint pain Gait analysis - walking and running	Check for presence of tibial varum, tibial torsion, uncompensated rearfoot varus and limb length discrepancy (include shoe wear pattern) Instigate the iliotibial band stretching regime (see Table 11), with a quadriceps- and adductor-strengthening programme Ice massage to painful area at lateral aspect of knee Advise reduction in athletic activity
2	Commence physical therapies, e.g. cortisone iontorphoresis or ultrasound and ice massage	Stabilizing orthoses and/or foot and ankle taping, ± heel lift Continue stretching programme ± massage Non-steroidal anti-inflammatory (10-day course of 400 mg ibuprofen qds) Stop all athletic activity if pain does not resolve
3	Magnetic resonance imaging/computed tomographic scan to knee joint area	Refer to orthopaedics
Most cases will resolve with one treatment; more severe cases will require a second visit and some will require orthopaedic referral.

Table 6: Iliotibial band-stretching regime

Muscle group	Action (hold for 5-10 seconds; repeat ×5, three times a day)
Hip abductor	Stand erect, legs straight, feet together; stretch trunk (on frontal plane) towards the unaffected leg
Iliotibial band	Lie on a bench on the unaffected side, with the unaffected hip and knee slightly flexed, in order to maintain balance; flex the affected hip and straighten the affected knee so that the affected leg hangs off the bench; allow the iliotibial band of the affected leg to be stretched by gravitational pull Lie on a bench on the affected side with the affected leg in line with the body and the hip and knee locked; flex the unaffected (upper) leg; place the hands on the bench immediately under the shoulder and push the trunk upwards as far as possible to apply stretch to the lateral area of the affected leg
Upper iliotibial band	Stand erect; with affected leg behind normal leg; stretch trunk (on frontal plane) towards unaffected side
Lower iliotibial band	Stand erect as above, with the knee of the affected leg slightly flexed and hips rotated (on transverse plane) towards affected leg; stretch trunk (on frontal plane) towards the unaffected side
Iliotibial band and hamstrings	Stand erect, with the affected leg behind the normal leg so that the knee of the affected leg rests on the posterior aspect of the non-affected knee; rotate the trunk (on transverse plane) away from the affected leg and attempt to touch the heel of the affected leg

Table 7: Grades and characteristics of medial tibial stress syndrome (MTSS)

Grade	Characteristic
1	Pain on palpation of the anteromedial (or posteromedial) area of tibial crest No pain during activity or exercise
2	Pain after activity or exercise No pain during activity or exercise
3	Pain during activity or exercise Pain after activity or exercise
4	Pain and discomfort during normal walking Continual pain during activity or exercise

Table 8: Phased treatment approach to medial tibial stress syndrome (MTSS)

Presentation	Treatment
Phase 1: acute phase	Cessation of exercise activity until all pain resolves RICE(P)
Phase 2: rehabilitation phase	Deep compartment muscle exercise to strengthen the deep fascial-bone interface and reduce tension on the deep fascial insertion, in order to decrease pain and swelling and prevent fascial scarring
Phase 3: functional phase	Use of antipronatory/functional orthoses, strapping or taping in order to strengthen the fascial-bone interphase and prevent further excessive tension on the tibia
Phase 4: return to activity	Phased and gradual return to normal levels of activity

Table 9: Presentations of nerve trunk irritation in the foot

Neuroma/lesion	Involved nerve	Location
Proximal tarsal tunnel syndrome	Branches of the posterior tibial nerve	Medial ankle area
Distal tarsal tunnel syndrome Jogger's foot	Medial plantar nerve	Between navicular tuberosity and belly of abductor hallucis
Distal tarsal tunnel syndrome Baxter's neuritis	Lateral plantar nerve	Between bellies of abductor hallucis, quadratus plantae and abductor digiti quinti minimi
Joplin's neuroma	Medial plantar nerve proper	Medial area of first metatarsal head
Houser's neuroma	First plantar intermetatarsal nerve	Between 1 and 2 metatarsals
Heuter's neuroma	Second plantar intermetatarsal nerve	Between 2 and 3 metatarsals
Morton's neuroma	Third plantar intermetatarsal nerve	Between 3 and 4 metatarsals
Islen's neuroma	Fourth plantar intermetatarsal nerve	Between 4 and 5 metatarsals

Table 10: Accessory bones in the foot

Accessory bone in the foot	Location
Os tibiale externum (accessory navicular)	Within tibialis posterior tendon, adjacent to proximal part of navicular tuberosity
Os trigonum	Posterior margin of talus
Os peroneum	Within peroneus longus tendon, adjacent to inferior lateral border of cuboid/calcaneocuboid joint
Os vesalianum	Adjacent to fifth metatarsal base
Os intermetatarseum	Between bases of first and second metatarsals
Os interphalangeus	Within insertion of flexor hallucis longus tendon, adjacent to plantar area of hallux interphalangeal joint

Table 11: Presentations of nerve trunk irritation in the foot

Neuroma/lesion	Involved nerve	Location
Proximal tarsal tunnel syndrome	Branches of the posterior tibial nerve	Medial ankle area
Distal tarsal tunnel syndrome Jogger's foot	Medial plantar nerve	Between navicular tuberosity and belly of abductor hallucis
Distal tarsal tunnel syndrome Baxter's neuritis	Lateral plantar nerve	Between bellies of abductor hallucis, quadratus plantae and abductor digiti quinti minimi
Joplin's neuroma	Medial plantar nerve proper	Medial area of first metatarsal head
Houser's neuroma	First plantar intermetatarsal nerve	Between 1 and 2 metatarsals
Heuter's neuroma	Second plantar intermetatarsal nerve	Between 2 and 3 metatarsals
Morton's neuroma	Third plantar intermetatarsal nerve	Between 3 and 4 metatarsals
Islen's neuroma	Fourth plantar intermetatarsal nerve	Between 4 and 5 metatarsals

Sjögren's syndrome

a symptom complex marked by keratoconjunctivitis sicca and xerostomia often occurring in association with other inflammatory disorders such as immune-mediated arthritis and systemic lupus erythematosus. Reported in dogs.