Intravenous administration of colchicine.

LETTERS
Figure 1. Pemio-like reaction
Unusual pernio-like reaction to sulindac
To the Editor:
I wish to report an unusual pernio-like reaction
to sulindac (Clinoril) that should be of interest to rheumatologists, since the reaction may resemble certain
cryophenomena seen in vasculitic and connective tissue
disorders.
A 48-year-old man began to have arthralgias in
shoulders, wrists, and small joints of the hands and feet
in late 1978. Results of an examination were normal, as
were sedimentation rate, rheumatoid factor, and antinuclear antibody tests. Despite trials of salicylates and
naproxen, he developed progressive morning stiffness,
fatigue, and definite synovitis of several metatarsophalangeal joints.
In January 1979, he was placed on sulindac 200
mg twice a day. Ten days later he reported painful tips
of the second and third toes bilaterally. He reported no
unusual cold exposure, other than normal Minnesota
winter living. He was receiving no other medications,
had no previous similar episodes, and had no history of
diabetes, claudication, Raynaud’s phenomenon, or upper extremity symptoms.
Examination revealed changes as shown in Figure 1, consisting of swelling, purple discoloration, red
papules, and desquamation of the distal aspects of several toes. Complete blood count, cold agglutinins,
cryoglobulins, cryofibrinogens, sedimentation rate, and
serologic test for syphilis were all either normal or negative. Sulindac was discontinued, and the lesions resolved over 2 weeks.
During the next year, he developed typical seronegative rheumatoid arthritis. He used a number of
1215
other antiinflammatory drugs without any similar reaction. In November 1980, he took 3 doses of 200 mg of
sulindac out of curiosity. Within 24 hours he developed
identical reactions in several toes. Again, there was no
associated unusual cold exposure. The changes resolved
in 1 week without residua.
The manufacturers of sulindac are aware of reports of similar reactions in 2 women who developed
Raynaud-like changes in the hands after brief exposure
to sulindac (S. L. Kasdin, personal communication). My
patient’s reaction was not Raynaud’s-like but rather resembled pernio, or “chilblains” (Herman EW, Kezis JS,
Silvers DN: A distinctive variant of pernio. Arch Dermatol 1 17:26-28, 1981).
Physicians should be aware of this reaction in
patients on Clinoril, particularly patients in whom such
“cryophenomena” might cause diagnostic confusion.
JAMESL. REINERTSEN,
MD
Department of Rheumatology
St. Louis Park Medical Center
5000 West Thirty-Ninth Street
Minneapolis, MN 55416
Intravenous administration of colchicine
To the Editor:
The intravenous administration of colchicine is
an accepted therapeutic modality for patients with
gouty arthritis (1,2). In addition, recent reports suggest
that intravenous colchicine may be the treatment of
choice in acute pseudogout (3,4). Our rheumatology
service saw an alcoholic patient who presented with
acute gouty arthritis. Since the patient had gastritis, we
felt that it would be prudent to avoid oral administration of colchicine or nonsteroidal antiinflammatory
agents which might irritate the gastrointestinal tract. Intravenous colchicine appeared to be the appropriate alternative.
Colchicine solution is extremely caustic (sodium
hydroxide may be added to adjust the pH). Accidental
extravasation of the solution may cause severe local irritation and tissue necrosis (5). Thus, it has been standard
practice to dilute the solution prior to injection (6) and
often, to administer it through an established intravenous line. To our surprise, a resident physician directed our attention to the current product labeling for
injectable colchicine which states that “colchicine injection should not be diluted with or injected into intravenous tubing containing 0.9% sodium chloride, 5%
LETTERS
1216
dextrose injection or any other fluid which would even
slightly change the pH of the colchicine solution since
this may cause precipitation.”
Because this is a revision of previous package labeling, we directed inquiries to the Eli Lilly Company,
the only pharmaceutical concern currently supplying
colchicine for intravenous use. We were informed that
this change resulted from communications to them from
physicians who had noted precipitates in solutions following dilution of colchicine with dextrose or saline. As
a consequence, the company restudied batches of injectable colchicine produced over the last several years but
to date has been unable to identify a specific contaminant. Using normal saline as diluent, they have not
found significant precipitation. It has been decided to
shorten the “out-date’’ time to 4 years, and we have
been informed that future product inserts will state that
if the solution of colchicine is to be diluted, 0.9% Sodium Chloride Solution USP XX be used, while recommending against the use of 5% dextrose solution or any
solution containing a bacteriostatic agent (7).
Physicians should, of course, discard any solution in which a precipitate is noted. Precipitate is best
seen by holding a solution against a dark background
with light directed at the solution from the side. In any
event, it would be judicious to use an intravenous system equipped with a final filter when giving diluted colchicine.
DAVID
J. NASHEL,
MD
Chief, Rheumatology Section
Veterans Administration Medical Center
50 Irving Street, N W
Washington, DC 20422
1. McCarty DJ: Pathogenesis and treatment of crystal-induced inflammation, Arthritis and Allied Conditions. Edited by DJ McCarty. Philadelphia, Lea & Febiger, 1979, p
1257
2. Kelley WN: Gout and related disorders of purine metabolism, Textbook of Rheumatology. Vol. 2. Edited by WN
Kelley, ED Harris, S Ruddy, CB Sledge. Philadelphia, WB
Saunders, 1981, p 1421
3. Tabatabia MR,Cummings NA: Intravenous colchicine in
the treatment of acute pseudogout. Arthritis Rheum
23:370-374, 1980
4. Spilberg I, McLain D, Simchowitz L, Berney S: Colchicine
and pseudogout. Arthritis Rheum 23: 1062-1063, 1980
5 . Wallace SL: The treatment of gout. Arthritis Rheum
15:317-323, 1972
6. Wyngaarden JB, Kelley WN: Gout and Hyperuricemia.
New York, Grune and Stratton, 1976, pp 466471
7. Dyke R: Eli Lilly Company, personal communication
Table 1. Incidence of HLA-B27 in J R A patients
Onset.
No. patients
B27+
96
6
11
14
-
-
1
8
50
Males and females
A
P
0
I
Males only
A
P
0
*A
-
acute onset; P = polyarticular, 0 = oligoarticular.
On the heterogeneity of HLA association in
juvenile rheumatoid arthritis
To the Editor:
In response to a recent article entitled “Heterogeneity of HLA Associations in Systemic Onset Juvenile
Rheumatoid Arthritis” by Glass and Litvin (I), we
would like to contribute some information about the
presence of different HLA antigens in the various subgroups of juvenile rheumatoid arthritis (JRA).
The results described in this letter were already
discussed at our Rheumatology Congress in 1978 (2).
Our experience was based on the typing of 31
JRA patients, 6 with the acute onset form, 11 with the
polyarticular form, and 14 with oligoarticular form. Diagnosis conformed to American Rheumatism Association criteria (3); most antisera used for HLA typing
have been accepted by the international workshop.
B27 antigen was present in 27% of patients of the
entire group. Its incidence rose to 85% in males with oligoarticular form and tended to be higher in patients
older than 10 (Table 1). Bw35 incidence was higher in
patients with the acute form ( 5 of 6) as shown in Table
2. We did not take into account this result, however, because of the small number of subjects and the high incidence of this antigen in our control group (32.09%).At
the present time, our cases have almost doubled, and
Bw35 is present in 6W0 of the patients with acute onset
JRA (4); therefore, our previous report about the incidence of B27 in the oligoarticular form is substantially
confirmed (5).
Table 2. Acute onset J R A