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Oral contraceptives and ANA positivity.

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7. Papoian R, Pillarisetty R, and Tala1 N: Immunologic regulation of spontaneous antibodies to DNA and RNA. I I .
Sequential switch from IgM to IgG in NZB/NZW FI mice.
Immunology 32:75, 1977
8. Ravechk ES, Klassen L, Steinberg AD: Sex differences in
the formation of anti-T cell antibodies. Arthritis Rheum
(abstract) 20: 132, 1977
9. Cram DL, Epstein JH, Tuffanelli DL: Lupus erythematosus and porphyria. Arch Dermatol 108:779-784. 1973
Failure of Cobra Venom Factor to Inhibit
Antigen-Induced Arthritis
To the Editor:
A component of cobra venom (CoF) is known to
deplete complement in serum ( 1 ). Previous work has
shown that complement depletion by C o F can inhibit
chemotaxis into inflammatory fluid ( 2 ) . Since an immune complex arthritis can be created in rabbit knee
joints (3), we investigated the effect of complement depletion by C o F on antigen-induced arthritis in rabbits.
A total of 13 New Zealand white rabbits were
used. All were sensitized by repeated subcutaneous injections of bovine serum albumin (BSA) combined with
Freund’s adjuvant. After 8 weeks serum levels of antibody to BSA were measured by radial immunodiffusion
and revealed satisfactory titers in each rabbit, ranging
from 0.93 to 4.05 mg/ml. During this sensitization period purified CoF was prepared and assayed according
to Ballow (4).
Six of the animals received 300 units/kg of CoF
intraperitoneally. The following day all the animals were
sedated and given an injection of 1 mg of BSA into one
knee joint space and saline into the other knee. Three of
the rabbits that received CoF.and 4 that did not were
sacrificed 24 hours later. The other 3 rabbits that had
received CoF initially were given daily intravenous injections of 100 units/kg of CoF, while the other 3 rabbits were given intravenous injections of saline during
the next 2 weeks. At the end of this time period all
remaining rabbits were sacrificed.
Serum samples obtained just prior to sacrifice
revealed no change in complement levels in the control
animals, whereas those receiving the C o F had depletions
of complement to about 20% or less of levels present at
the start of the investigation. Histological examination
of the knee joints revealed no significant difference in the
degree of inflammation between the animals (either
acute or prolonged regimen) that received the CoF and
those that received saline. Perhaps higher doses of systemic C o F or local instillation would have lowered complement levels to a point where the inflammatory re-
sponse would be noticeably reduced. The difficulties of
both approaches (economic and technical) precluded
their evaluation in aborting this form of experimental
Department of Pathology
HSC, SUNY at Stony Brook
Stony Brook, NY I I794
This work was performed under a grant by the New
York Chapter of The Arthritis Foundation.
Nelson RA Jr.: A new concept of immunosuppression in
hypersensitivity reactions and in transplantation immunity.
Surv Ophthalmol I1:498-505, 1966
Wiener, S. Lendvai S, Rogers B, et al: Nonimmune chemotaxis in vivo-inhibition by complement depletion with
cobra factor. Am J Pathol 73:807-815, 1973
Steinberg M E , McCrae CR, Cohen LD, et al: Pathogenesis
of antigen-induced arthritis. Clin Orthop 97:248-260, 1973
Ballow M , Cochrane CG: Two anticomplementary factors
in cobra venom: hemolysis of guinea pig erythrocytes by
one of them. J lmmunol 103:944-952, 1969
Oral Contraceptives
and ANA Positivity
To the Editor:
Oral contraceptives are suspected of causing a
positive ANA with or without symptoms of SLE. We
report of a patient with localized scleroderma who,
while on an oral contraceptive agent, ethynodiol diacetate with mestranol, developed arthralgias, rapid sedimentation rate, and a positive ANA, all of which subsided when the birth control pill was discontinued.
A 25-year-old woman presented with arthralgias
of the knees, hands, wrists, and ankles. The pain worsened with activity and subsided with rest. An acute
episode of arthritis of the hands, feet, and knees had
developed 3 months earlier when she had been given
penicillin to treat fever and sore throat. The swelling
subsided but muscular pain persisted. The only medication she had been taking was the birth control pill which
she had taken since 1968. She did not have Raynaud’s
phenomenon, chest symptoms, sun or drug sensitivities,
mucocutaneous lesions, or renal or CNS disease.
Skin changes and muscle atrophy of the right
lower leg had been present since 13 years of age. A niece
has similar skin changes.
Fig 1. Fioe views (?\'the legs of a 25-year-old
wotiian with localized linear sclcrodertna.
Examination revealed muscle atrophy of the medial aspect of the right lower leg. On the overlying skin
there were atrophic and hyperpigmented patches. A few
telangiectatic spots were visible on the right upper arm
and chest. The dorsum of the left wrist and the skin
above the eyebrows were hyperpigmented.
Laboratory data included a sedimentation rate of
45 and A N A positive X 2. Renal function studies were
within normal limits, C-3 128 mg%.
The oral contraceptive was discontinued. A
month later the A N A was negative and the sedimentation rate had slowed to 21. Her arthralgias ceased.
In a prospective study, the relation between oral
contraceptive agents and a positive A N A was in-
vestigated. Four of 82 patients developed ANA while on
oral contraceptives. There were, however, no controls
( I ) . Rodnan found no convincing evidence of internal
involvement in the localized forms of scleroderma or of
overlap between these conditions and progressive systemic sclerosis (2). Dubois has reported 3 patients with
both localized scleroderma and SLE (3). Familial scleroderma is rare; only several documented instances have
been reported (4).
Grunow Memorial Medical Building
926 East McDowell Road
Phoenix, Arizona 85006
Dubois EL: Lupus Erythematosus. Second edition. Los
Angeles, University of Southern California Press, 1974, p
2. Rodnan G P Progressive systemic sclerosis (scleroderma),
Arthritis and Allied Conditions. Eighth edition. Edited by
J L Hollander, DJ McCarty Jr. Philadelphia, Lea & Febiger, 1972, pp 962-1005.
3. Dubois EL, Chandor S, Friou GJ, et al: Progressive systemic sclerosis (PSS) and localized scleroderma (morphea)
with positive LE cell test. Medicine 50199-222. 1900
4. Wuthrich RC, Roenigk HH Jr, Steck WD: Localized
scleroderma. Arch Dermatol 3:98-100, 1900
Homozygosity for HLA-B27 in Psoriatic
Arthritis and Spondylitis
To the Editor:
The Journal published a recent report on homozygosity at the B locus for allele B27 and impact on
rheumatic disease expression ( I ) . We would like to present the case of a young man with severe psoriatic arthritis and spondylitis who is homozygous for HLA-B27.
A 29-year-old French Canadian male developed
psoriasis at age 22 beginning with his elbows, knees, and
scalp and was treated successfully with coal tars. When
he was 25, asymmetric polyarthritis began in his knees
and ankles associated with low back and neck pain and
stiffness. The arthritis progressed, causing him to stop
working at age 26. He was hospitalized in 1974 and his
arthritis was treated with salicylates, with mild improvement. His arthritis and psoriasis both flared in 1976 and
he was again hospitalized. There was no history of
urethritis, uveitis, or conjunctivitis.
Physical examination revealed generalized psoriasis with the exception of his hands. Pitting of his nails
was noted. The complete fusion of his cervical and lumbar spine resulted in marked disability. Little active
synovitis was present, but there were flexion deformities
of both shoulders, elbows, hips, and right knee. In addition there was a severe valgus deformity of his right knee
and left foot.
Laboratory studies showed a hematocrit of 38%.
white blood count of 11,800, and Wintrobe sedimentation rate of 52 mm/hour. His urinalysis, latex fixation,
and antinuclear antibody were negative. HLA typing
revealed the phenotype of AW 31, B27. X-rays of the
axial skeleton demonstrated fusion of the cervical and
lumbar spine and both sacroiliac joints. Asymmetric
erosions were evident in the PIP joints, wrists, shoulders, knees, ankles, and feet. There was narrowing of the
right hip joint, collapse of the right medial tibia1 plateau,
and dislocation of the M P joints of the left foot.
The patient was started on methotrexate 2.5 mg
4 1 2 hr for three doses weekly. This has produced considerable improvement in both his rash and his functional ability.
The patient’s mother, father, and sister were interviewed and examined. None had a history of psoriasis, musculoskeletal complaints, or any abnormalities
on examination. HLA typing revealed his mother to be
AW 25, A W 3 I , B 18, B27: the father and sister were AW
24, AW 31, B7, B27. it is of interest that the patient’s
grandmothers were second cousins. Two way mixed
lymphocyte cultures were performed. There was no reaction between the patient and either of his parents.
This patient had severe axial and peripheral psoriatic arthritis. Of 50 patients with psoriatic arthritis
seen in the past 3 years at our institution he has the most
severe case. He is also the only patient found to be
homozygous for B27. I n addition this patient also demonstrated homozygosity at the A and D loci. The influence of homozygosity for A locus antigens on disease
is unknown. I n fact, disease associations with HLAAW31 antigen have not been described, and none of
our other patients with psoriatic arthritis had this allele.
The possibility of disease associated with D locus antigens exists. A recent paper by Chused showed that Sjo
grens syndrome is primarily associated with HLA-DWj
and only secondarily with HLA B8 (2). However in
anklylosing spondylitis, D locus antigen association has
not been found (3). Similar studies in psoriatic arthritis
have not been done.
Thus definite consideration must be given to our
patient’s homozygosity at the B locus as being significant. HLA-B27 has been reported in 60% of patients
with psoriatic spondylitis but only in 11% of those with
peripheral arthritis alone (4).
A study on British Columbian Coastal Indians
has documented a remarkably high prevalence of anky-
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contraceptive, positivity, ana, oral
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