Hydrallazine-induced Sjögren's syndrome
2
Hydrallazine-induced Sj6gren's syndrome A. Darwaza, P-J. Lamey and J. M. C. Connell Department of Oral Medicine and Pathology, Glasgow Dental Hospital and School and Department of Medicine, Western infirmary, Glasgow, Scotland A. Darwaza, P.-J. Lamey and J. M. C. Connell: Hydrallazine-induced Sjtgren's syndrome. Int. J. Oral Maxillofac. Surg. 1988; 17." 92-93. Abstract. 4 years after initiation of therapy with hydrallazine hydrochloride (for treatment of hypertension), a 60-year-old male patient developed clinical features of Sj6gren's syndrome, with immunological features of drug-induced systemic lupus erythematosus. In addition, the patient described rheumatoid arthritis-like symptoms and had reduced lacrimal and parotid salivary flow, but lacked the typical features of Sj6gren's syndrome on labial gland biopsy. 1 year after discon- tinuation of hydrallazine therapy, the clinical parameters returned to normal. Key words: Sj6gren's syndrome; autoimmuni- ty, hydrallazine Accepted for publication 14 September 1987 Sj6gren's syndrome occurs most fre- quently in females of middle age, has a female to male ratio of around 10:117 and the concept of autoimmunopathy is often implicated in its aetiology l°. Cur- rent nomenclature differentiates be- tween primary Sjtgren's (dry eyes and dry mouth) and secondary Sj6gren's syndrome (dry eyes or dry mouth with a connective tissue disorder) 8. Rheuma- toid arthritis is the most common sys- temic accompaniment of secondary Sj6gren's syndrome 16 with a reported in- cidence of 30% 60% 1 . Immunological findings in serum include antigamma- globulin antibodies, antinuclear anti- bodies, and rheumatoid factor (in 75% of cases) even if a connective tissue dis- ease is not presentIL Antibodies directed against salivary gland duct cell have been reported in 50% of patients I and the LE test is positive in about 20% of patients in addition to hypergammaglo- bulinaemia 7. Case report A 60-year-old male had been attending the Medical Clinic at the Western Infirmary, Glasgow, for some years with hypertension, and had been treated for 4 years with hydral- lazine hydrochloride 50 mg t.i.d., an anti- hypertensive agent. Previous medical history revealed treated renal tuberculosis in 1978 and 4 operations to the right eye after retinal detachment. Hydrallazine was discontinued in July, 1984because of joint pain, principally affecting the metocarpophalangeal joints, and proximal inter-phalangeal joints. There- after, these symptoms resolved. At that time, antinuclear factor was positive at a titre of 1/256, although DNA-binding capacity was normal. He was then referred to the Oral Medicine Unit at Glasgow Dental Hospital with the complaint of a dry mouth and eye dis- comfort. The dry mouth was confirmed by maximal stimulated partotid salivary flow rates using a Cadsson Crittenden cup and 1 ml of 10% citric acid. This demonstrated a flow of 0.5 ml/min from the right parotid and 0.2 ml/min from the left parotid which are below the lower normal limit (0.7 ml/min) 2. In addition, by the Schirmer test, he had decreased lacrimal flow rates with only 4 mm wetting in 5 rain from the right eye, and 6 mm wetting in 5 rain from the left eye. The antinuclear factor titre was 1/1000 homogen- ous and membranous; DNA binding capacity was 25.5% which is normal. By sulphadimi- dine testing, his acetylator status was 41% (slow acetylator). A labial gland biopsy of 5 gland lobules showed the presence of mild, non-specific chronic sialadenitis only. The patient received artificial tears (Tears naturelle Alcon) and saliva replacement ther- apy (Saliva Orthana Nydegaard, UK). Over the next year, salivary gland flow rates and Schirmer testing of lacrimal gland function returned to normal. In March 1986, the stimulated salivary flow rates were 1.9 ml/ rain from both the right and left parotid. The Schirmer test gave results of 15 mm wetting in 5 min from both eyes. Discussion Several reports have been published in the past few years presenting cases of drug-induced Sicca syndrome (primary Sj6gren's). In one such case, a 67-year- old male patient developed clinical and laboratory features of Sicca syndrome 2 weeks after initiation of therapy with 1.2 mg per day of quinidine sulphate and resolution followed discontinuation of the drug 12. Busulfan (0.5 to 6 mg/ day) given to a patient with chronic my- eloleukaemia for 9 years resulted in a severe Sicca syndrome with an Addison- ian-like syndrome in a 52-year-old woman 15. Thiabendazole, an antihel- minthic drug, was implicated in in- ducing intraheptic cholestasis and Sicca syndrome in a 55-year-old man 14. Sicca complex and cholangiostatic jaundice was also reported in 2 members of a family treated by thiabendazole and all the manifestations disappeared after discontinuation of the drug 5. Systemic lupus erythematosus (SLE) is a known side-effect of hydrallazine therapy3.6,13, particularly after long-term therapy with more than 100 mg/day 3. Drug-induced lupus erythematosus syn- dromes as caused by hydrallazine, pro- cainamides and isoniazid may be due to circulating immune complexes4. In this case, the drug or a reactive metabolite may have interacted with nuclear ma- terial to allow the formation of antinu- clear antibodies. Hydrallazine-induced lupus is very uncommon in fast acetyl- ators 4, 9 and this "~s consistent with the slow acetylator status of the present case. The clinical and laboratory findings of this case initially were of low salivary flow rates, low lacrimal flow rates (Schirmer test), an antinuclear factor tit- re of 1/1000 membranous and hom- ogenous, all of which strongly suggest the presence of Sj6gren's syndrome as- sociated with SLE. However, the nor- mal DNA binding capacity points to a drug-induced condition, as does the lack of typical features of Sj6gren's syn- drome in labial gland biopsy.
Transcript of Hydrallazine-induced Sjögren's syndrome
Hydrallazine-induced Sj6gren's syndrome
A. Darwaza, P-J. Lamey and J. M. C. Connell Department of Oral Medicine and Pathology, Glasgow Dental Hospital and School and Department of Medicine, Western infirmary, Glasgow, Scotland
A. Darwaza, P.-J. Lamey and J. M. C. Connell: Hydrallazine-induced Sjtgren's syndrome. Int. J. Oral Maxillofac. Surg. 1988; 17." 92-93.
Abstract. 4 years after initiation of therapy with hydrallazine hydrochloride (for treatment of hypertension), a 60-year-old male patient developed clinical features of Sj6gren's syndrome, with immunological features of drug-induced systemic lupus erythematosus. In addition, the patient described rheumatoid arthritis-like symptoms and had reduced lacrimal and parotid salivary flow, but lacked the typical features of Sj6gren's syndrome on labial gland biopsy. 1 year after discon- tinuation of hydrallazine therapy, the clinical parameters returned to normal.
Key words: Sj6gren's syndrome; autoimmuni- ty, hydrallazine
Accepted for publication 14 September 1987
Sj6gren's syndrome occurs most fre- quently in females of middle age, has a female to male ratio of around 10:117 and the concept of autoimmunopathy is often implicated in its aetiology l°. Cur- rent nomenclature differentiates be- tween primary Sjtgren's (dry eyes and dry mouth) and secondary Sj6gren's syndrome (dry eyes or dry mouth with a connective tissue disorder) 8. Rheuma- toid arthritis is the most common sys- temic accompaniment of secondary Sj6gren's syndrome 16 with a reported in- cidence of 30% 60% 1 . Immunological findings in serum include antigamma- globulin antibodies, antinuclear anti- bodies, and rheumatoid factor (in 75% of cases) even if a connective tissue dis- ease is not presentIL Antibodies directed against salivary gland duct cell have been reported in 50% of patients I and the LE test is positive in about 20% of patients in addition to hypergammaglo- bulinaemia 7.
Case report
A 60-year-old male had been attending the Medical Clinic at the Western Infirmary, Glasgow, for some years with hypertension, and had been treated for 4 years with hydral- lazine hydrochloride 50 mg t.i.d., an anti- hypertensive agent. Previous medical history revealed treated renal tuberculosis in 1978 and 4 operations to the right eye after retinal detachment. Hydrallazine was discontinued in July, 1984 because of joint pain, principally affecting the metocarpophalangeal joints, and proximal inter-phalangeal joints. There- after, these symptoms resolved. At that time, antinuclear factor was positive at a titre of 1/256, although DNA-binding capacity was normal.
He was then referred to the Oral Medicine Unit at Glasgow Dental Hospital with the complaint of a dry mouth and eye dis- comfort. The dry mouth was confirmed by maximal stimulated partotid salivary flow rates using a Cadsson Crittenden cup and 1 ml of 10% citric acid. This demonstrated a flow of 0.5 ml/min from the right parotid and 0.2 ml/min from the left parotid which are below the lower normal limit (0.7 ml/min) 2. In addition, by the Schirmer test, he had decreased lacrimal flow rates with only 4 mm wetting in 5 rain from the right eye, and 6 mm wetting in 5 rain from the left eye. The antinuclear factor titre was 1/1000 homogen- ous and membranous; DNA binding capacity was 25.5% which is normal. By sulphadimi- dine testing, his acetylator status was 41% (slow acetylator). A labial gland biopsy of 5 gland lobules showed the presence of mild, non-specific chronic sialadenitis only.
The patient received artificial tears (Tears naturelle Alcon) and saliva replacement ther- apy (Saliva Orthana Nydegaard, UK). Over the next year, salivary gland flow rates and Schirmer testing of lacrimal gland function returned to normal. In March 1986, the stimulated salivary flow rates were 1.9 ml/ rain from both the right and left parotid. The Schirmer test gave results of 15 mm wetting in 5 min from both eyes.
Discussion
Several reports have been published in the past few years presenting cases of drug-induced Sicca syndrome (primary Sj6gren's). In one such case, a 67-year- old male patient developed clinical and laboratory features of Sicca syndrome 2 weeks after initiation of therapy with 1.2 mg per day of quinidine sulphate and resolution followed discontinuation of the drug 12. Busulfan (0.5 to 6 mg/
day) given to a patient with chronic my- eloleukaemia for 9 years resulted in a severe Sicca syndrome with an Addison- ian-like syndrome in a 52-year-old woman 15. Thiabendazole, an antihel- minthic drug, was implicated in in- ducing intraheptic cholestasis and Sicca syndrome in a 55-year-old man 14. Sicca complex and cholangiostatic jaundice was also reported in 2 members of a family treated by thiabendazole and all the manifestations disappeared after discontinuation of the drug 5.
Systemic lupus erythematosus (SLE) is a known side-effect of hydrallazine therapy3.6,13, particularly after long-term therapy with more than 100 mg/day 3. Drug-induced lupus erythematosus syn- dromes as caused by hydrallazine, pro- cainamides and isoniazid may be due to circulating immune complexes 4. In this case, the drug or a reactive metabolite may have interacted with nuclear ma- terial to allow the formation of antinu- clear antibodies. Hydrallazine-induced lupus is very uncommon in fast acetyl- ators 4, 9 and this "~s consistent with the slow acetylator status of the present case.
The clinical and laboratory findings of this case initially were of low salivary flow rates, low lacrimal flow rates (Schirmer test), an antinuclear factor tit- re of 1/1000 membranous and hom- ogenous, all of which strongly suggest the presence of Sj6gren's syndrome as- sociated with SLE. However, the nor- mal DNA binding capacity points to a drug-induced condition, as does the lack of typical features of Sj6gren's syn- drome in labial gland biopsy.
Sj6gren's syndrome 93
There is some debate in relation to the criteria for the diagnosis o f Sj6gren's syndrome. Some authors consider a positive labial gland biopsy as pathog- nomic 18 while others would make the diagnosis on clinical grounds alone 19. However, the point has previously been made that labial gland biopsy is an ad- junctive parameter rather than a sine qua non for diagnosis z°.
Al though Sicca syndrome (primary Sj6gren's) has been previously reported as a drug-induced condit ion with sev- eral drugs, this case is particularly inter- esting as a case o f apparent hydrattazi- ne-induced secondary Sj6gren's syn- drome.
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Address: P.-J. Lamey Department of Oral Medicine and Pathology Glasgow Dental Hospital and School 378 Sauehiehall Street Glasgow, G2 3JZ Scotland
