Sjogren's syndrome - oral and dental considerations in HIV/AIDS patients
Rheumatologic and Musculoskeletal Manifestations of HIV
Nancy Lane, MD, University of California San FranciscoOctober 1998
HIV-Associated Salivary Gland Disease (Sjogren's Syndrome and Diffuse Infiltrative Lymphocytosis)
[credit: http://www.hiv.va.gov/vahiv?page=pr-kb-00&post=0&kb=kb-04-01-15&tp=Clinical%20Manifestations&tpage=prtop05-00-rr&sec=06 retrieved with permission.]
A syndrome superficially resembling Sjogren's syndrome has been found in adult and pediatric patients infected with HIV or human T-cell leukemia virus type I (HTLV-I). It is characterized by massive parotid enlargement and xerostomia and is referred to as diffuse idiopathic lymphocytic syndrome (DILS).( 33-42 ) DILS can appear at any stage of HIV disease (at any CD4 level). The actual incidence of DILS in children or adults is unknown; over 50 cases have been reported in the literature.
Clinical Presentation
Exocrine gland manifestations of DILS include xerophthalmia (dry eyes), xerostomia (dry mouth), salivary gland enlargement, and arthralgias.
The extraglandular involvement in DILS may include lymphocytic hepatitis due to CD8 lymphocytic infiltration of the liver. Infiltration of the lung causing lymphocytic interstitial pneumonitis (LIP) is the most serious manifestation of this disorder; it can progress to pulmonary insufficiency. Other organs and systems affected include the gastrointestinal tract, kidney (most commonly as type IV renal tubular acidosis), thymus, and nervous system.( 41 ) Gastric infiltration may result in a syndrome resembling linitis plastica. Lymphadenopathy is a frequent finding.
Sjögren's syndrome or DILS in HIV-infected patients differs from idiopathic Sjögren's syndrome in the following ways:
· Most reported cases are in males (which reflects the predominance in the United States of HIV infection in males)
· There can be massive parotid swelling and large neck masses
· Arthritis is absent
· There is somewhat less xerophthalmia and more frequent extrasalivary lymphoid infiltration, including lymphocytic interstitial pneumonitis, and lymphocytic infiltration of the gastrointestinal, neurologic, and reticuloendothelial systems
· Results of serologic studies are negative (including tests for cytoplasmic RNA antibodies and Ro and La antibodies)
· There are increased numbers of CD8+ (suppressor-cytotoxic) T cells in the blood and tissue
· There is no associated increase in HLA-DR2 or DR3 cell-surface antigens
Pathogenesis
DILS seems to reflect a distinct host immune response occurring in persons with the cell-surface antigen type HLA-DR5.( 43 ) Although clinically it resembles classic Sjogren's syndrome, DILS is distinguished by a CD8+ and CD29+ lymphocyte infiltrate, extraglandular visceral involvement, a paucity of autoantibodies, and a strong association with HLA-DR5 in African American patients with DILS, and with HLA-DR6 and HLA-DR7 in Caucasian patients. The extent of CD8 lymphocyte infiltration in the lungs and parotid glands correlates with the numbers of peripheral circulating CD8 cells.
CD8 lymphocytes that bear CD29 suppress replication of HIV in simian immunodeficiency virus (SIV) in vitro ( 44,45 ); therefore circulating CD8 cells in patients with DILS may suppress HIV replication.( 26 )
Differential Diagnosis of Sicca Syndrome in HIV-Infected Patients
The differential diagnosis of chronic salivary gland enlargement in HIV-infected patients includes bacterial sialoadenitis, viral infections (such as mumps, Epstein-Barr virus, and possibly HIV), tumors, and DILS. The clinician should recommend HIV testing in a patient with a chronic Sjogren-like syndrome.
All evaluations of patients complaining of dry eyes or dry mouth should include a careful drug history to rule out iatrogenic illness, such as from drugs like tricyclic antidepressants and antihistamines.
The identification of a Sjogren-like illness in a young patient with atypical or uncommon clinical features should suggest HIV-associated salivary gland disease. Clinical and laboratory features suggesting this condition include young age (under 40 years of age), high-risk group (homosexual, bisexual, injection drug user, transfusion recipient, hemophiliac), male gender (79% of non-HIV-related Sjogren's syndrome occurs in females), generalized lymphadenopathy, and negative autoimmune serologic results.
Treatment
Treatment of HIV-associated Sjogren's syndrome is mostly symptomatic. Artificial saliva, used 2 to 3 times per day, reduces symptoms of dry mouth. Patients should avoid sugar because of the high incidence of cavities and periodontal disease associated with inadequate salivary flow. Artificial tears applied 2 to 3 times per day can help prevent corneal ulcerations. Also, due to salivary gland enlargement, recurrent sinus, middle ear, and oral cavity infections can occur. Treatment with antibiotics appropriate to the culture and infection site is usually effective for these problems.
Immunosuppressive therapy should be used only when patients are in life-threatening situations such as pulmonary insufficiency or renal disease. One report described DILS patients with pulmonary involvement and respiratory insufficiency who responded to treatment with prednisone (1 mg/kg/day) and chlorambucil.( 41 ) Three patients showed clinical improvement and resolution of pulmonary infiltrates; none developed opportunistic infections. A number of HIV-infected patients with salivary gland enlargement showed striking decreases in parotid enlargement when treated with zidovudine (AZT),( 41 ) and there are anecdotal reports that patients with lymphocytic interstitial pneumoniae respond to AZT. We suggest that HIV-infected patients with DILS receive anti-HIV drugs.
References:
33. Pahwa S, Kaplan M, Fikrig S, Pahwa R, Sarngadharan MG, Popovic M, Gallo RC.
Spectrum of human T-cell lymphotropic virus type III infection in children. Recognition of symptomatic, asymptomatic, and seronegative patients. JAMA. 2299-305
[PubMed ID: 3007791*]
34.Ulirsch RC, Jaffe ES.
Sjogren's syndrome-like illness associated with the acquired immunodeficiency syndrome-related complex. Hum Pathol. 1063-8
[PubMed ID: 3653877*]
35.Couderc LJ, D'Agay MF, Danon F, Harzic M, Brocheriou C, Clauvel JP.
Sicca complex and infection with human immunodeficiency virus. Arch Intern Med. 898-901
[PubMed ID: 3579441*]
36. DeClerck LS, Coultenye MM, DeBroe ME, et al. Acquired immunodeficiency syndrome mimicking Sjögren's syndrome and systemic lupus erythematosus. Arthritis Rheum 1988;31:272-275.
37.Gordon JJ, Golbus J, Kurtides ES.
Chronic lymphadenopathy and Sjogren's syndrome in a homosexual man. N Engl J Med. 1441-2
[PubMed ID: 6333638*]
38.Lecatsas G, Houff S, Macher A, Gelman E, Steis R, Reichert C, Masur H, Sever JL.
Retrovirus-like particles in salivary glands, prostate and testes of AIDS patients. Proc Soc Exp Biol Med. 653-5
[PubMed ID: 2984694*]
39.Ryan JR, Ioachim HL, Marmer J, Loubeau JM.
Acquired immune deficiency syndrome--related lymphadenopathies presenting in the salivary gland lymph nodes. Arch Otolaryngol. 554-6
[PubMed ID: 4026669*]
40.Jaffe ES, Ulirsch RC.
Salivary gland lymphadenopathies associated with AIDS: reply. Hum Pathol. 1120
[PubMed ID: 3417296*]
41. Itescu S, Brancato LJ, Buxbaum J, et al. Sjögren's syndrome associated with HIV infection. Clin Res 1988;36:599A.
42. Itescu S, Brancato LJ, Gregersen PK, et al. Diffuse infiltrative CD8 lymphocytosis in HIV infection is associated with a particular subtype of HLA-DR5. Clin Res 1989;37:412A
Nancy Lane, MD, University of California San FranciscoOctober 1998
HIV-Associated Salivary Gland Disease (Sjogren's Syndrome and Diffuse Infiltrative Lymphocytosis)
[credit: http://www.hiv.va.gov/vahiv?page=pr-kb-00&post=0&kb=kb-04-01-15&tp=Clinical%20Manifestations&tpage=prtop05-00-rr&sec=06 retrieved with permission.]
A syndrome superficially resembling Sjogren's syndrome has been found in adult and pediatric patients infected with HIV or human T-cell leukemia virus type I (HTLV-I). It is characterized by massive parotid enlargement and xerostomia and is referred to as diffuse idiopathic lymphocytic syndrome (DILS).( 33-42 ) DILS can appear at any stage of HIV disease (at any CD4 level). The actual incidence of DILS in children or adults is unknown; over 50 cases have been reported in the literature.
Clinical Presentation
Exocrine gland manifestations of DILS include xerophthalmia (dry eyes), xerostomia (dry mouth), salivary gland enlargement, and arthralgias.
The extraglandular involvement in DILS may include lymphocytic hepatitis due to CD8 lymphocytic infiltration of the liver. Infiltration of the lung causing lymphocytic interstitial pneumonitis (LIP) is the most serious manifestation of this disorder; it can progress to pulmonary insufficiency. Other organs and systems affected include the gastrointestinal tract, kidney (most commonly as type IV renal tubular acidosis), thymus, and nervous system.( 41 ) Gastric infiltration may result in a syndrome resembling linitis plastica. Lymphadenopathy is a frequent finding.
Sjögren's syndrome or DILS in HIV-infected patients differs from idiopathic Sjögren's syndrome in the following ways:
· Most reported cases are in males (which reflects the predominance in the United States of HIV infection in males)
· There can be massive parotid swelling and large neck masses
· Arthritis is absent
· There is somewhat less xerophthalmia and more frequent extrasalivary lymphoid infiltration, including lymphocytic interstitial pneumonitis, and lymphocytic infiltration of the gastrointestinal, neurologic, and reticuloendothelial systems
· Results of serologic studies are negative (including tests for cytoplasmic RNA antibodies and Ro and La antibodies)
· There are increased numbers of CD8+ (suppressor-cytotoxic) T cells in the blood and tissue
· There is no associated increase in HLA-DR2 or DR3 cell-surface antigens
Pathogenesis
DILS seems to reflect a distinct host immune response occurring in persons with the cell-surface antigen type HLA-DR5.( 43 ) Although clinically it resembles classic Sjogren's syndrome, DILS is distinguished by a CD8+ and CD29+ lymphocyte infiltrate, extraglandular visceral involvement, a paucity of autoantibodies, and a strong association with HLA-DR5 in African American patients with DILS, and with HLA-DR6 and HLA-DR7 in Caucasian patients. The extent of CD8 lymphocyte infiltration in the lungs and parotid glands correlates with the numbers of peripheral circulating CD8 cells.
CD8 lymphocytes that bear CD29 suppress replication of HIV in simian immunodeficiency virus (SIV) in vitro ( 44,45 ); therefore circulating CD8 cells in patients with DILS may suppress HIV replication.( 26 )
Differential Diagnosis of Sicca Syndrome in HIV-Infected Patients
The differential diagnosis of chronic salivary gland enlargement in HIV-infected patients includes bacterial sialoadenitis, viral infections (such as mumps, Epstein-Barr virus, and possibly HIV), tumors, and DILS. The clinician should recommend HIV testing in a patient with a chronic Sjogren-like syndrome.
All evaluations of patients complaining of dry eyes or dry mouth should include a careful drug history to rule out iatrogenic illness, such as from drugs like tricyclic antidepressants and antihistamines.
The identification of a Sjogren-like illness in a young patient with atypical or uncommon clinical features should suggest HIV-associated salivary gland disease. Clinical and laboratory features suggesting this condition include young age (under 40 years of age), high-risk group (homosexual, bisexual, injection drug user, transfusion recipient, hemophiliac), male gender (79% of non-HIV-related Sjogren's syndrome occurs in females), generalized lymphadenopathy, and negative autoimmune serologic results.
Treatment
Treatment of HIV-associated Sjogren's syndrome is mostly symptomatic. Artificial saliva, used 2 to 3 times per day, reduces symptoms of dry mouth. Patients should avoid sugar because of the high incidence of cavities and periodontal disease associated with inadequate salivary flow. Artificial tears applied 2 to 3 times per day can help prevent corneal ulcerations. Also, due to salivary gland enlargement, recurrent sinus, middle ear, and oral cavity infections can occur. Treatment with antibiotics appropriate to the culture and infection site is usually effective for these problems.
Immunosuppressive therapy should be used only when patients are in life-threatening situations such as pulmonary insufficiency or renal disease. One report described DILS patients with pulmonary involvement and respiratory insufficiency who responded to treatment with prednisone (1 mg/kg/day) and chlorambucil.( 41 ) Three patients showed clinical improvement and resolution of pulmonary infiltrates; none developed opportunistic infections. A number of HIV-infected patients with salivary gland enlargement showed striking decreases in parotid enlargement when treated with zidovudine (AZT),( 41 ) and there are anecdotal reports that patients with lymphocytic interstitial pneumoniae respond to AZT. We suggest that HIV-infected patients with DILS receive anti-HIV drugs.
References:
33. Pahwa S, Kaplan M, Fikrig S, Pahwa R, Sarngadharan MG, Popovic M, Gallo RC.
Spectrum of human T-cell lymphotropic virus type III infection in children. Recognition of symptomatic, asymptomatic, and seronegative patients. JAMA. 2299-305
[PubMed ID: 3007791*]
34.Ulirsch RC, Jaffe ES.
Sjogren's syndrome-like illness associated with the acquired immunodeficiency syndrome-related complex. Hum Pathol. 1063-8
[PubMed ID: 3653877*]
35.Couderc LJ, D'Agay MF, Danon F, Harzic M, Brocheriou C, Clauvel JP.
Sicca complex and infection with human immunodeficiency virus. Arch Intern Med. 898-901
[PubMed ID: 3579441*]
36. DeClerck LS, Coultenye MM, DeBroe ME, et al. Acquired immunodeficiency syndrome mimicking Sjögren's syndrome and systemic lupus erythematosus. Arthritis Rheum 1988;31:272-275.
37.Gordon JJ, Golbus J, Kurtides ES.
Chronic lymphadenopathy and Sjogren's syndrome in a homosexual man. N Engl J Med. 1441-2
[PubMed ID: 6333638*]
38.Lecatsas G, Houff S, Macher A, Gelman E, Steis R, Reichert C, Masur H, Sever JL.
Retrovirus-like particles in salivary glands, prostate and testes of AIDS patients. Proc Soc Exp Biol Med. 653-5
[PubMed ID: 2984694*]
39.Ryan JR, Ioachim HL, Marmer J, Loubeau JM.
Acquired immune deficiency syndrome--related lymphadenopathies presenting in the salivary gland lymph nodes. Arch Otolaryngol. 554-6
[PubMed ID: 4026669*]
40.Jaffe ES, Ulirsch RC.
Salivary gland lymphadenopathies associated with AIDS: reply. Hum Pathol. 1120
[PubMed ID: 3417296*]
41. Itescu S, Brancato LJ, Buxbaum J, et al. Sjögren's syndrome associated with HIV infection. Clin Res 1988;36:599A.
42. Itescu S, Brancato LJ, Gregersen PK, et al. Diffuse infiltrative CD8 lymphocytosis in HIV infection is associated with a particular subtype of HLA-DR5. Clin Res 1989;37:412A