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Sjogren Syndrome


Synonyms, Key=20 Words, and Related Terms: keratoconjunctivitis sicca, = xerostomia=20
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 eMedicine Journal = > Ophthalmology > Connective Tissue = Disorders > Sjogren = Syndrome=20
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AUTHOR INFORMATION = Section 1 of 10    <= IMG=20 height=3D10 alt=3D"Click here to go to the next section in this = topic"=20 src=3D"http://www.emedicine.com/images/next3.gif" width=3D31 = align=3Dmiddle=20 border=3D0>

Authored by = James V Aquavella, MD, Director of Corneal Research = Laboratory=20 and Corneal Fellowship Program, Professor of Ophthalmology, Department = of=20 Ophthalmology, University of Rochester School of Medicine

Coauthored by Shobha Boghani, MD, Assistant = Professor,=20 Department of Ophthalmology, Strong Memorial Hospital, University of = Rochester

James V Aquavella, MD, is a member of the following medical = societies: American Academy of Ophthalmology, American College of Surgeons, American Medical Association, Association for Research in Vision and=20 Ophthalmology, Contact Lens = Association of=20 Ophthalmologists, and International=20 College of Surgeons

Edited by Fernando H Murillo-Lopez, MD, Instructor,=20 Department of Ophthalmology, Bolivian National Institute of = Ophthalmology;=20 Donald S Fong, MD, MPH, Assistant Clinical Professor of = Ophthalmology, UCLA School of Medicine; Consulting Physician, Department = of=20 Ophthalmology, Southern California Permamente Medical Group; = Christopher=20 J Rapuano, MD, Co-Chairman of Refractive Surgery Department, = Associate=20 Professor, Cornea Service, Wills Eye Hospital, Jefferson Medical = College;=20 Lance L Brown, OD, MD, Ophthalmologist, Regional Eye = Center,=20 Affiliated With Freeman Hospital and St John's Hospital, Joplin, = Missouri; and=20 Hampton Roy, Sr, MD, Clinical Associate Professor, = Department=20 of Ophthalmology, University of Arkansas for Medical Sciences=20

Author's = Email: James=20 V Aquavella, MD 3D"Click
Editor's = Email: Fernando=20 H Murillo-Lopez, MD

eMedicine Journal, July 11 2002, Volume 3, = Number=20 7
INTRODUCTION = Section 2 of 10    3D"Click

Background= :=20 Sj=F6gren syndrome is an autoimmune disorder consisting of=20 keratoconjunctivitis sicca (KCS) and xerostomia (ie, dry mouth), which = often=20 involves nasal and vaginal mucous membranes. Other systemic = manifestations, most=20 commonly rheumatoid arthritis or systemic lupus erythematosus, can be=20 associated. Although there were several reports of this condition in the = late=20 1800s, it was the classic monograph written in 1933 by Henrik Sj=F6gren, = the=20 Swedish ophthalmologist, who described the clinical and pathological = findings of=20 this syndrome affecting menopausal women.

Pathophysiology: Two types of Sj=F6gren syndrome = exist,=20 primary and secondary. Primary Sj=F6gren syndrome has 2 subsets, as = follows:=20 patients who have systemic immune dysfunction but no defined connective = tissue=20 dysfunction, and patients who lack evidence of systemic immune = dysfunction or a=20 defined connective tissue disease.=20

Secondary Sj=F6gren syndrome includes patients who have a defined = connective=20 tissue disease, most commonly rheumatoid arthritis.=20

Besides rheumatoid arthritis and systemic lupus erythematosus, other=20 autoimmune diseases less commonly seen with Sj=F6gren syndrome are = progressive=20 systemic sclerosis, Hashimoto thyroiditis, polymyositis, polyarteritis = nodosa,=20 and Waldenstr=F6m macroglobulinemia.=20

Patients with Sj=F6gren syndrome are at an increased risk for = developing=20 lymphomas and other lymphoproliferative disorders. This increased risk = has been=20 attributed to a reduction of natural killer cell activity.

Frequency:

  • Internationally: One epidemiologic study in = Sweden=20 reported the prevalence of Sj=F6gren syndrome as approximately 0.4%. =

Mortality/Morbidity: Severe dry eyes can cause = corneal=20 scarring, ulceration, infection, and even perforation.=20

Sex: Female-to-male ratio is 9:1.=20

Age: Although primarily a disease of postmenopausal = women,=20 age can range from 22-70 years, with the average age being 43 years. = Sj=F6gren=20 syndrome has been reported in children who developed recurrent parotid = gland=20 enlargement.
CLINICAL Section 3 of 10   <= IMG=20 height=3D10 alt=3D"Click here to go to the previous section in = this topic"=20 src=3D"http://www.emedicine.com/images/back3.gif" width=3D31 = align=3Dmiddle=20 border=3D0> =

History:=20 Ocular signs and symptoms of Sj=F6gren syndrome are similar to = those seen=20 in dry eye states.

    • Burning
    • Stinging
    • Itching
    • Foreign body sensation
    • Lid irritation and swelling
    • Photophobia
    • Ocular fatigue
    • Mucoid discharge

Physical: Two important clues that the patient may = have dry=20 eyes include diurnal fluctuation of symptoms and exacerbation of = symptoms during=20 specific activities or environmental conditions. It is common for = symptoms to=20 become worse at night or upon awakening because tear production = decreases during=20 sleep. Air conditioning, smoky or windy conditions, and airplane travel = may=20 worsen the symptoms by creating excessive drying of the deficient tear = film.=20 Activities, such as reading, working at the computer, or watching = television,=20 may make the patient more symptomatic, as the blink rate decreases with=20 prolonged visual effort.

  • Sj=F6gren syndrome consists of a triad of dry eyes, dry mouth, and = an=20 autoimmune disease. At least 2 of the 3 clinical components need to be = present=20 to qualify for diagnosis. For a definitive diagnosis of Sj=F6gren = syndrome, all=20 criteria below should be met; however, 3 of the 4 criteria are = sufficient for=20 a presumptive diagnosis. The most comprehensive diagnostic criteria = include=20 the following:
    • An abnormally low Schirmer test with clinical evidence of KCS = defined by=20 the presence of rose bengal or fluorescein staining
    • Objective evidence of decreased salivary gland = flow
    • Evidence of lymphocytic infiltration of the labial salivary = glands,=20 proven by a biopsy specimen containing at least 4 glandular lobules = with an=20 average of at least 2 foci of 50 or more lymphocytes/4 = mm2 of=20 tissue
    • Evidence of a systemic autoimmune process as manifested by the = presence=20 of serum autoantibodies, including antinuclear antibody (ANA), = rheumatoid=20 factor (RF), or Sj=F6gren syndrome specific antibodies (ie, anti-Ro = [SS-A],=20 anti-La [SS-B]).
  • Three objective findings are useful in determining the ocular = component of=20 Sj=F6gren syndrome.
    • Absence of nasal-lacrimal reflex tearing
    • Degree of ocular surface alteration by rose bengal or = fluorescein=20 staining
    • Presence of autoantibodies in the serum
  • Nasal stimulation may increase tearing dramatically in patients = who do not=20 have Sj=F6gren syndrome.

Causes:

  • Recent developments in the fields of immunology and molecular = biology have=20 contributed significantly to the understanding of the pathogenesis of = Sj=F6gren=20 syndrome. One report in 1985 showed human leukocyte antigen DR = (HLA-DR)=20 expression in epithelial cells of salivary gland biopsy specimens = taken from=20 patients with Sj=F6gren syndrome. The predominant lymphocytic = infiltration=20 consisted of helper T cells. Other studies found that = lymphoproliferation in=20 the lacrimal glands consisted predominantly of B and CD4 lymphocytes = along=20 with a small percentage of CD8 lymphocytes.
  • The exact etiology for the pathologic changes that occur in = Sj=F6gren=20 syndrome has not been determined. Epstein-Barr virus (EBV) may play a = role.=20 One study found that parotid saliva samples and salivary gland biopsy=20 specimens from 8 of 20 patients with Sj=F6gren syndrome contained EBV = DNA by=20 slot blot hybridization. Another study using polymerase chain reaction = (PCR)=20 reported detection of EBV genomic sequences in peripheral blood = mononuclear=20 cells, lacrimal glands, and tears of primary Sj=F6gren = syndrome.
  • EBV genomes can be detected in 35% of normal lacrimal glands. EBV = genotype=20 analysis by PCR revealed that only type I EBV genomes could be = detected in 35%=20 of normal lacrimal glands. EBV genotype analysis by PCR revealed that = only=20 type II EBV nuclear antigens (EBNA-2-deleted) gene sequences were = amplified=20 from normal lacrimal glands. In contrast, type I, but not = EBNA-2-deleted EBV=20 sequences, were amplified from Sj=F6gren syndrome lacrimal gland = biopsy. All of=20 this information suggests that persistent EBV infection plays a role = in the=20 lacrimal gland pathology of Sj=F6gren syndrome.
  • Two types of pathologic changes have been observed in the salivary = glands,=20 the benign epithelial lesion occurring primarily in the parotid = glands, and=20 focal lymphocytic sialadenitis occurring in other major and minor = salivary=20 glands. These benign lymphoepithelial lesions may be associated with = or=20 transform into lymphomas.
  • Immunogenetics
    • In 1977, human leukocyte antigen DR3 (HLA-DR3)(DW3) was reported = to be=20 associated with Sj=F6gren syndrome. Another study found that primary = Sj=F6gren=20 syndrome had a significantly increased frequency of human leukocyte = antigen=20 B8 (HLA-B8) and DR3 antigens, whereas patients with secondary = Sj=F6gren=20 syndrome had an increased frequency of DR4 antigens.
    • HLA-type is correlated strongly with the production of SS-A (Ro) = and=20 SS-B (La) autoantibodies. Both Ro and La positivity is seen most = commonly=20 with primary Sj=F6gren syndrome, and these patients usually have = HLA-B8=20 haplotype.
DIFFERENTIALS = Section 4 of 10   3D"Click

Blepharitis, Adult =
Dry Eye Syndrome =
Uveitis, Juvenile = Rheumatoid=20 Arthritis


Other Problems to be Considered:

Superficial punctate keratopathy
Filamentary = keratopathy
Neurotrophic=20 keratopathy
Exposure keratopathy

WORKUP Section 5 of 10   =

Lab Studies:

    • Tear osmolarity
    • Fluorescein clearance test
    • Tear function index
  • All of these tests have variable specificity and sensitivity. = Controversy=20 surrounds the validity of many of these objective tests.

Imaging Studies:

  • Parotid flow rate can determine xerostomia. Radionuclide scan and=20 sialography of the parotid glands are other methods to assess salivary = gland=20 function.

Other Tests:

  • Clinical tests may be useful to establish an aqueous tear=20 deficiency.
    • Reduced tear break-up time
    • Schirmer test
    • Rose bengal staining
    • Lissamine green B
    • Hamano pheno/red thread test
  • All of these tests have variable specificity and sensitivity. = Controversy=20 surrounds the validity of many of these objective tests.

Procedures:

  • Biopsy of accessory salivary glands is preferred over biopsy of = lacrimal=20 glands, because it is easily accessible and less potential for = complications=20 exists. Under local infiltration with 2% lidocaine with epinephrine, 5 = or 6=20 lobules of accessory salivary glands are removed and fixed in=20 formalin.
Histologic Findings: Impression = cytology of=20 buccal mucosa may be helpful. In one study, this technique showed a 97%=20 agreement with labial salivary gland biopsy. Conjunctival impression = cytology in=20 early onset of Sj=F6gren syndrome may show an increased number of goblet = cells. In=20 severe and long-standing cases, the conjunctiva shows loss of goblet = cells and=20 squamous metaplasia.=20

In addition, histopathology of conjunctival specimens may show = evidence of=20 squamous metaplasia and keratinization of the conjunctival epithelium.=20 Lymphocytic infiltration of the accessory lacrimal glands also may = occur.

TREATMENT Section 6 of 10   

Medical = Care:=20

  • To avoid toxicity from preservatives (eg, benzalkonium chloride),=20 preservative-free, small-dose units offer an alternative. Lubricating=20 ointments play an important role in moistening the ocular surface = during sleep=20 when the tear production is decreased. Using the ointment during the = day can=20 blur the vision significantly. Sustained release lubricant = preparations (eg,=20 Lacrisert) were tried in hope that they would dissolve slowly over a = 12-hour=20 period; however, problems of blurry vision and displacement = occurred.
  • Existing tears of the patient can be conserved by using punctal = occlusion=20 to decrease the drainage of the tears. A small lateral tarsorrhaphy = can=20 decrease the ocular surface area and provide significant relief.=20 Humidification of the environment also improves patient comfort = significantly.=20 It can be achieved by wearing swimmer's goggles or taping a plastic = shield or=20 wrap over the eyelids.
  • Agents to increase tear secretion, such as bromhexine and = 3-isobutyl=20 1-methylxanthine (IBMX), have been tried outside of the US. No = decrease in=20 rose bengal staining or subjective improvement in ocular irritation = was noted=20 with the use of bromhexine.
  • Cyclosporin A, a powerful suppressor of T-cell function, has been=20 evaluated for treatment of Sj=F6gren syndrome. In one report, oral = cyclosporin A=20 (5 mg/kg/d) or placebo was used in a double-masked trial for treatment = of=20 primary Sj=F6gren syndrome. A subjective improvement of the dry mouth = symptoms=20 in most of the patients occurred; however, only 20% of the patients = noted=20 improvement in ocular irritation. No difference in aqueous tear = production by=20 Schirmer testing between the 2 groups was reported.
  • A pilot trial of 1% cyclosporin A ophthalmic ointment showed = marked=20 subjective improvement in symptoms control compared to the placebo = group.=20 Patients treated with topical cyclosporin A had less ocular surface = rose=20 bengal staining than control subjects, but no difference in Schirmer = test=20 values or tear break-up times between the 2 groups occurred. Topical = 2%=20 cyclosporin A solution has been reported to successfully treat para = central=20 corneal ulcers in patients with rheumatoid arthritis and secondary = Sj=F6gren=20 syndrome. Cyclosporin A is a secretogogue for the lacrimal gland; the = exact=20 mechanism is unknown.=20

  • Systemic use of corticosteroids or androgen hormones may suppress = the=20 immune-mediated lacrimal gland disease of Sj=F6gren syndrome and may = improve=20 lacrimal gland secretory function.=20

  • In 1985, Tseng et al reported the use of tretinoin (all=20 trans-retinoic acid) ointment for treating various dry eye=20 conditions, which included a group who had keratitis sicca associated = with=20 Sj=F6gren syndrome. This trial was nonrandomized, and all of the = research=20 subjects reported a subjective improvement and a reduction of rose = bengal=20 staining and squamous metaplasia. However, this finding was not = duplicated in=20 a multicenter, placebo-controlled, double-masked study. This trial = failed to=20 find a beneficial effect of tretinoin.

Consultations:

  • A consultation with an internist or rheumatologist may be = warranted if a=20 systemic autoimmune process is suspected.
  • Patients with Sj=F6gren syndrome have a higher incidence of dental = and=20 gynecological problems and should be seen for routine dental and = gynecological=20 care.
MEDICATION = Section 7 of 10   

Artificial = tears and=20 lubricating ointments are widely available as nonprescription items. = Individual=20 formulations have proprietary pH, osmolarity, viscosity, and retention = time=20 characteristics. In general, these items are available compounded with=20 preservatives or in a nonpreserved sterile state. For individuals who = are=20 sensitive, nonpreserved preparations frequently are selected. Most = practitioners=20 feel that 4-6 times a day utilization of the liquid tear substitutes = with=20 preservatives is not unreasonable, but at higher utilization levels, the = nonpreservative forms may provide less ocular surface toxicity over the = long=20 term.=20

Tretinoin was found to be effective in increasing comfort and = reducing rose=20 bengal staining in squamous metaplasia in one study. Numerous subsequent = studies=20 have failed to confirm any positive benefit of this medication when used = independently or in conjunction with surface lubricants.=20

In the form of small soluble rods, these can be placed in the = inferior fornix=20 and are expected to dissolve and biodegrade over a 12-hour period. = Problems=20 associated with insertion, comfort, blurred vision, and the tendency for = displacement have rendered this an infrequently used form of therapy.=20

Bromhexine and IBMX are used outside of the United States. While they = are=20 available in Europe, there is no documentation that their use is = associated with=20 subjective or objective improvement. The mode of action is to directly = affect=20 the lacrimal gland, increasing secretion. Oral pilocarpine also has been = used as=20 a secretory agent to increase lacrimal gland production but is not = approved in=20 the United States for such use.

Drug Category: Immunosuppressants -- = Cyclosporin=20 A has been used orally to suppress T-cell function in patients who have = had=20 organ transplants. In Sj=F6gren syndrome, its use is experimental and = reports have=20 not been encouraging. One or two percent cyclosporin A in liquid or = ointment=20 form has been used topically following the initial report that its use = increased=20 lacrimal gland function in dogs.
Drug Name
 Cyclosporin A (Sandimmune, = Neoral) --=20 Acts to suppress T-cell formation and, while not currently FDA = approved,=20 has been used clinically to increase lacrimal gland function in = Sj=F6gren=20 syndrome.
Until the FDA approved drug is available, it must = be=20 compounded and thus does not have a preservative, increasing the = risk for=20 secondary infection.
Adult Dose Apply 1 or 2% solution (in = olive oil or=20 corn oil); frequency not established; 2-6 times/d suggested
Pediatric Dose Not established
Contraindications Documented hypersensitivity; = uncontrolled=20 hypertension or malignancies; do not administer concomitantly with = PUVA or=20 UVB radiation in psoriasis since it may increase risk of cancer
Interactions Carbamazepine, phenytoin, = isoniazid,=20 rifampin, and phenobarbital may decrease cyclosporine = concentrations;=20 azithromycin, itraconazole, nicardipine, ketoconazole, = fluconazole,=20 erythromycin, verapamil, grapefruit juice, diltiazem, = aminoglycosides,=20 acyclovir, amphotericin B, and clarithromycin may increase = cyclosporine=20 toxicity; acute renal failure, rhabdomyolysis, myositis, and = myalgias=20 increase when taken concurrently with lovastatin
Pregnancy C - Safety for use during = pregnancy has=20 not been established.=20
Precautions Evaluate renal and liver = functions often=20 by measuring BUN, serum creatinine, serum bilirubin and liver = enzymes; may=20 increase risk of infection and lymphoma; reserve IV use only for = those who=20 cannot take PO
Drug Category:=20 Corticosteroids -- Systemic corticosteroids have been = used in a=20 variety of inflammatory conditions for many years. Because of the = limited=20 efficacy and the high incidence of complication, they are not widely = used.=20 Topical corticosteroids are widely available in a variety of dosages, = often=20 combined with antibiotic and preservatives, and may be useful for the = short term=20 in treatment of associated ocular surface inflammatory conditions. They = are=20 usually available in 5, 10, or 15 mL dispenses or in 1/8 ounce ointment = form.
Drug Name
 Prednisolone (Pred Forte) -- = Not=20 advocated for long-term use in Sj=F6gren syndrome. Acute episodes = of ocular=20 surface inflammation or secondary uveitis may require short-term = or=20 periodic usage.
Adult Dose 1-2 gtt 1-6 times/d
Pediatric Dose Not established; 1-4 gtt/d = suggested
Contraindications Documented hypersensitivity; = viral,=20 fungal, or tubercular infections
Interactions None reported
Pregnancy C - Safety for use during = pregnancy has=20 not been established.=20
Precautions Caution in hypertension; known = to cause=20 cataract formation with chronic use; fungal invasion should be = suspected=20 in any persistent corneal ulceration where a corticosteroid has = been used=20 or is in use (fungal cultures should be taken when=20 appropriate)
FOLLOW-UP Section 8 of 10    =

Further Outpatient Care:

Deterrence/Prevention:

  • Wearing spectacles or goggles is beneficial in preventing ocular = surface=20 drying secondary to exposure.
  • The placement of air conditioning or heating ducts at home and at = the=20 workplace should be considered.
  • Avoidance of desiccating environments, such as proximity of open=20 fireplaces or smoke-filled rooms, should be considered.
  • Systemic medications also can adversely affect the ocular surface. = Reduction or elimination of such medications could decrease the drying = of the=20 ocular surface.

Complications:

  • Severe dry eyes can cause corneal scarring, ulceration, infection, = and=20 even perforation.

Prognosis:

  • While the prognosis is good for most patients, eyes with corneal=20 infection, ulceration, or perforation have a much more guarded=20 prognosis.

Patient Education:

  • Patients should know to seek ophthalmic care if their eyes become = red or=20 painful, or if they develop a mucopurulent discharge.
MISCELLANEOUS = Section 9 of 10    <= IMG=20 height=3D10 alt=3D"Click here to go to the next section in this = topic"=20 src=3D"http://www.emedicine.com/images/next3.gif" width=3D31 = align=3Dmiddle=20 border=3D0>

Medical/Legal Pitfalls:

  • In any of these individuals who are treated with = immunosuppression, it is=20 extremely important that the ophthalmologist be aware of the patient's = status=20 regarding follow-up laboratory studies. It is also important for these = patients to have contact with their internist and/or immunologist. = This should=20 be noted clearly on the medical record at each patient = visit.
  • Should nonpreserved medications be used and/or hydrophilic bandage = lenses,=20 one must always be aware of the significant potential for secondary = infection.=20 These risks should be explained to the patient prior to initiating = these forms=20 of therapy. The utilization of a prophylactic antibiotic is the = standard of=20 care.
  • In the presence of a significantly compromised ocular surface, = there is=20 some reluctance to used topical anesthetic and applanation tonometry. = While=20 the intraocular pressure recording may not be necessary at each = particular=20 visit, it should clearly be performed and its results indicated on the = chart=20 at periodic intervals. Additionally with the anterior segment ocular = surface=20 disorder, routine follow-up care of the posterior segment also may be=20 compromised. Care should be taken to perform either dilated fundus=20 examinations or, at the very least, fundus examinations without = dilatation at=20 intervals that are appropriate for the patient's age and general=20 status.
BIBLIOGRAPHY = Section 10 of 10   =

  • Aguilar AJ, Fonseca L, Croxatto JO: Sjogren's syndrome: a = comparative=20 study of impression cytology of the conjunctiva and buccal mucosa, and = salivary gland biopsy. Cornea 1991 May; 10(3): 203-6[Medline].=20
  • Bloch KJ, Buchanan WW, Wohl MJ, Bunim JJ: Sjogren's syndrome. A = clinical,=20 pathological, and serological study of sixty-two cases. 1965. Medicine = (Baltimore) 1992 Nov; 71(6): 386-401; discussion 401-3[Medline].=20
  • Chused TM, Kassan SS, Opelz G, et al: Sjogren's syndrome = association with=20 HLA-Dw3. N Engl J Med 1977 Apr 21; 296(16): 895-7[Medline].=20
  • Daniels TE: Benign lymphoepithelial lesion and Sjogren's syndrome. = In:=20 Ellis GL, AuClair PL, eds. Surgical Pathology of the Salivary Glands. = WB=20 Saunders; 1991.=20
  • Drosos AA, Skopouli FN, Costopoulos JS, et al: Cyclosporin A (CyA) = in=20 primary Sjogren's syndrome: a double blind study. Ann Rheum Dis 1986 = Sep;=20 45(9): 732-5[Medline].=20
  • Fox RI, Robinson CA, Curd JG, et al: Sjogren's syndrome. Proposed = criteria=20 for classification. Arthritis Rheum 1986 May; 29(5): 577-85[Medline].=20
  • Fox RI, Pearson G, Vaughan JH: Detection of Epstein-Barr = virus-associated=20 antigens and DNA in salivary gland biopsies from patients with = Sjogren's=20 syndrome. J Immunol 1986 Nov 15; 137(10): 3162-8[Medline].=20
  • Lindahl G, Hedfors E, Klareskog L, Forsum U: Epithelial HLA-DR = expression=20 and T lymphocyte subsets in salivary glands in Sjogren's syndrome. = Clin Exp=20 Immunol 1985 Sep; 61(3): 475-82[Medline].=20
  • Manthrope R, Frost, Larsen K: Sjogren's Syndrome: A review with = emphasis=20 on immunological features. Allergy 1981; 36: 139-153.=20
  • Miyasaka N, Seaman W, Bakshi A, et al: Natural killing activity in = Sjogren's syndrome. An analysis of defective mechanisms. Arthritis = Rheum 1983=20 Aug; 26(8): 954-60[Medline].=20
  • Mizuno Y, Hara T, Hatae K, et al: Recurrent parotid gland = enlargement as=20 an initial manifestation of Sjogren syndrome in children. Eur J = Pediatr 1989=20 Feb; 148(5): 414-6[Medline].=20
  • Moutsopoulos HM, Chused TM, Mann DL, et al: Sjogren's syndrome = (Sicca=20 syndrome): current issues. Ann Intern Med 1980 Feb; 92(2 Pt 1): = 212-26[Medline].=20
  • Murillo-Lopez F, Pflugfelder SC: Disorders of tear production and = the=20 lacrimal system. In: Krachmer JH, ed. Cornea. Mosby Year Book; 1997: = 663-686.=20
  • Pepose JS, Akata RF, Pflugfelder SC, Voigt W: Mononuclear cell = phenotypes=20 and immunoglobulin gene rearrangements in lacrimal gland biopsies from = patients with Sjogren's syndrome. Ophthalmology 1990 Dec; 97(12): = 1599-605[Medline].=20
  • Pflugfelder SC, Huang AJ, Feuer W, et al: Conjunctival cytologic = features=20 of primary Sjogren's syndrome. Ophthalmology 1990 Aug; 97(8): 985-91[Medline].=20
  • Pflugfelder SC: Lacrimal gland epithelial and immunopathology of = Sjogren's=20 syndrome. In: Homma M ed. Proceedings of the IV International = Sjogren's=20 Syndrome Symposium, Kugler. Am Steleveen 1994.=20
  • Pflugfelder SC, Crouse C, Pereira I, Atherton S: Amplification of=20 Epstein-Barr virus genomic sequences in blood cells, lacrimal glands, = and=20 tears from primary Sjogren's syndrome patients. Ophthalmology 1990 = Aug; 97(8):=20 976-84[Medline].=20
  • Pflugfelder SC, Crouse CA, Monroy D, et al: Epstein-Barr virus and = the=20 lacrimal gland pathology of Sjogren's syndrome. Am J Pathol 1993 Jul; = 143(1):=20 49-64[Medline].=20
  • Pflugfelder SC, Whitcher JP, Daniels T: Sjogren's syndrome. In: = Pepose J=20 Holland G, Wilhelmin K, eds, Ocular Infection and Immunity. St. Louis: = Mosby.=20
  • Prause JV: Lacrimal and salivary secretion in Sjogren's syndrome: = The=20 effect of systemic treatment with Bromhexine. Acta Ophthalmol (Copen) = 1984;=20 62: 489-497.=20
  • Shearn MA: Sjogren's Syndrome. Major Problems in Internal = Medicine. Vol 2.=20 WB Saunders; 1971.=20
  • Sjogren, HS: Zur Kenntnis der Keratoconjunctivitis sicca (Kratitis = folliforms bei hypojunktion der tramemdrusen). Acta Ophthalmol = (Copenh) 1933;=20 11: 1-151.=20
  • Tabbara KF, Ostler HB, Daniels TE, et al: sjogren's syndrome: a=20 correlation between ocular findings and labial salivary gland = histology. Trans=20 Am Acad Ophthalmol Otolaryngol 1974 May-Jun; 78(3): OP467-78[Medline].=20
  • Tabbara KF: Clinical diseases of tear film. In: Smolin G, Thoft R, = eds.=20 Cornea: Scientific Foundations and Clinical Practice. 2nd ed. Little = Brown and=20 Co; 1987: 477-483.=20
  • Tsubota K: The importance of the Schirmer test with nasal = stimulation. Am=20 J Ophthalmol 1991 Jan 15; 111(1): 106-8[Medline].

NOTE:
Medicine is a constantly = changing=20 science and not all therapies are clearly established. New = research=20 changes drug and treatment therapies daily. The authors, editors, = and=20 publisher of this journal have used their best efforts to provide=20 information that is up-to-date and accurate and is generally = accepted=20 within medical standards at the time of publication. However, as = medical=20 science is constantly changing and human error is always = possible,=20 the authors, editors, and publisher or any other party involved = with the=20 publication of this article do not warrant the information in this = article=20 is accurate or complete, nor are they responsible for omissions or = errors=20 in the article or for the results of using this information. The = reader=20 should confirm the information in this article from other sources = prior to=20 use. In particular, all drug doses, indications, and = contraindications=20 should be confirmed in the package insert. FULL = DISCLAIMER=20
eMedicine Journal,=20 July 11 2002, Volume 3, Number 7

Sjogren= Syndrome=20 excerpt

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