CASE REPORTS

Polychondritis Resulting from Intravenous Substance Abuse ROBERTG. BERGER, M.D. ChapeiHi//, Northcarolina

R elapsing polychondritis is a relatively rare rheu- matic disease characterized by recurrent episodes

of inflammation involving nasal, auricular, and tra- cheal cartilage [1,2]. Non-erosive polyarthritis, vesti- buloauditory dysfunction, scleritis, aortitis, and small vessel vasculitis occur in a significant number of pa- tients with this illness [3]. Although immunologically mediated animal models of chondritis have been de- veloped [4-61, and antibodies to type II collagen have been demonstrated in patients with active chondritis [7,8], pathogenicity of these antibodies has not been established. This article describes a patient in whom acute polychondritis developed with identical features of the rheumatic disease after recreational intrave- nous injection of a multiple substance “cocktail.” The characteristics of the illness suggested a biochemical rather than immunologic mechanism for cartilage in- jury, and provided a unique opportunity for observa- tion of a human model of polychondritis.

CASE REPORT A previously healthy 26-year-old white man pre-

sented for evaluation 24 hours after intravenous self- administration of a bizarre combination of materials. For unknown reasons, the patient and his cousin be- lieved that the materials would provide a euphoric state. The patient denied previouslyusing intravenous drugs, though the cousin admitted to occasional intra- venous drug abuse with common “street” drugs. The “recipe” used included the following substances: 1 ta- blespoon of 31 percent hydrochloric acid (obtained by using a commercial brick cleaning agent); 1 tablespoon of ethyl ether (carburetor fluid); 1 tablespoon of tap water; and the waxy internal matrix of a mentholated nasal inhaler (Vicks inhaler containing l-desoxyephe- drine 50 mg, menthol, camphor, and bornyl acetate). The nasal inhaler material was dissolved into the other ingredients in a small metal bowl by warming using a cigarette lighter. The patient and his cousin injected approximately 1 to 2 ml of this mixture into antecubi- tal veins. Both stated that they experienced an imme- diate “rush.” One hour after injection, pain and discol- oration of several fingers distal to the injection site developed in the cousin. Approximately 24 hours after the injection, reddened painful eyes and headache de- veloped in both men. Shortly thereafter, the patient noted fever; generalized arthralgia that included the anterior costochondral junctions; swelling, pain, and redness of his nose and ears; and mild vertigo. Al- though these symptoms did not occur in the cousin, both men sought medical attention.

From the Division of Rheumatology/Immunology, University of North Car- olina School of Medicine, Chapel Hill, North Carolina. Requests for reprints

Office Building, Chapel Hill, North Carolina 27514. Manuscript recerved May 5. 1988. and accepted in revised form June 17, 1988.

On examination, the cousin was noted to have mod- erate scleritis and cyanosis of the index and middle fingers of the right hand with normal radial and ulnar pulses. The remainder of the examination was normal. Results of the laboratory examination were normal except for a slightly elevated white blood cell count. The outcome of digital arteriography was normal, and the patient was believed to have inadvertently per- formed an intra-arterial injection of the “recipe.” No further symptoms developed in the cousin other than skin sloughing of the involved fingers.

Physical examination of the patient 48 hours after injection was remarkable for a temperature of 38.4”C, intense bilateral scleritis, and marked erythema and edema of auricular pinna bilaterally and nasal carti- lage (Figure 1). Marked synovitis was present in all small and large joints including feet, hands, wrists, knees, and shoulders (Figure 2). Sternomanubrial, sternoclavicular, and costochondral areas were in- tensely inflamed, and the patient was unable to turn over or use his extremities secondary to his joint pain. The results of the neurologic examination revealed bilateral rotatory nystagmus and ataxia, and the pa- tient was unable to sit upright secondary to severe vertigo. Abnormal laboratory findings on admission included a white blood cell count of 26,000/mm3, a differential of 75 percent polymorphonuclear neutro- phils, 20 percent lymphocytes, and 5 percent mono- phils, and mildly elevated levels of serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and lactate dehydrogenase. The results of urinalysis were normal. Arthrocentesis of the left knee yielded inflammatory fluid with a white blood cell count of 23,000/mm3 (75 percent polymorphonu- clear neutrophils) and was negative for crystals under cross-polarized microscopic examination. Lumbar puncture was normal. Antinuclear antibody and rheu- matoid factor were negative. Total hemolytic comple- ment and serum immunoelectrophoresis were normal. Bacterial and fungal cultures of blood, cerebrospinal fluid, and synovial fluid yielded no growth. Biopsy examination of the right ear pinna showed loss of baso- philia and nuclear pyknosis of chondrocytes with peri- chondral mild inflammation, consistent with chondri- tis. Antibodies to type II collagen, measured by Dr. David Trentham using a modification of an enzyme- linked immunoassay developed for measurement of antibodies in the rat model of polychondritis [9], were not demonstrable in the patient’s serum.

The patient was treated with high-dose prednisone, which resolved the synovitis, auricular and nasal chon- dritis, and scleritis over three days. The ataxia and vertigo continued, and a severe sensorineural hearing loss developed. When prednisone was tapered after two weeks, the scleritis returned and prednisone was increased. The patient did not return for further ap- pointments and was lost to follow-up.

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POLYCHONDRITIS FROM INTRAVENOUS SUBSTANCE ABUSE / BERGER

COMMENTS This patient’s illness represents an acute polychon-

dritis with many of the signs and symptoms that occur in relapsing polychondritis. The intense nasal and au- ricular chondritis combined with scleritis and vestibu- loauditory symptoms are well described in relapsing polychondritis [lo-131. No other precipitating event for the chondritis other than the injection of the intra- venous mixture could be demonstrated by bacteriolog- ic or serologic evaluation. His arthritis and marked inflammation of costochondral and sternal cartilage were of greater intensity than the arthropathy associ- ated with relapsing polychondritis [14]. Synovial fluid analyses have not previously been reported in relaps- ing polychondritis. The synovial fluid in this patient was moderately inflammatory with a predominance of polymorphonuclear leukocytes, not unexpected in view of the intensity of his arthritis. The response of his cartilaginous inflammation to corticosteroid treat-

Figure 2. Inflammatory synovitis present in all small foot joints.

Figure 1. Intense scleral, ricular inflammation pre physic al examination.

nasal, and au- sent on initial

ment was consistent with the improvement described in previous series of patients with relapsing polychon- dritis [3]. The response of the scleritis proved to be dose dependent, and the vertigo and hearing loss were not steroid responsive.

Polychondritis in experimental animals has been in- duced by peritoneal injection of type II collagen with adjuvant. Biopsy examination of the auricular chon- dritis that occurs demonstrates immunoglobulin and complement deposition in involved cartilage [5]. Cir- culating IgG antibodies specific for type II collagen can be found in the serum of these animals and are believed to be pathogenic [6]. It is less clear that auto- immunity is causative in the human disease. Antibod- ies to type II collagen can be demonstrated in a major- ity of patients with active chondritis, but immune deposition in the involved cartilage itself is rare [5,8]. Small vessel vasculitis involving skin and kidney can occur but this is by no means universal, and immuno- chemical studies of these lesions are non-specific [15]. It is possible that the precipitating event in human polychondritis is biochemical, and the autoimmune phenomenon is a secondary occurrence.

This is the first report of a toxic exposure causing polychondritis. Several factors indicate that the carti- lage damage and resulting inflammation he demon- strated were caused by a direct biochemical effect of the “cocktail” he injected, rather than an immunologi- cally mediated mechanism. The illness occurred quite rapidly after injection of the material. The time course was much too short for a primary immune response, although an anamnestic immune response could have occurred within 24 to 48 hours. However, the patient denied prior sensitization to this combination of chemicals by previous intravenous abuse (though he had used a mentholated nasal inhaler topically be- fore); the results of serum complement studies were normal throughout his hospital course, and assay for antibodies against type II collagen in his serum were negative. In the patient’s cousin, only scleritis devel- oped and cartilage inflammation or vestibular symp- toms did not occur. The inadvertent intra-arterial in-

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jection he performed may have changed the tissue distribution of the materials and lessened the clinical syndrome he exhibited. Which component of the “cocktail” caused the damage or whether a new chemi- cal was created by the heating of camphor and other mentholated materials (the nasal inhaler matrix) with concentrated hydrochloric acid is an intriguing ques- tion we were not able to answer. None of the individual materials in the nasal inhaler has been reported to cause cartilage damage. Attempts at combining the “cocktail” materials using the patient’s recipe were made. Heating of the mixture resulted in volatilization of the ethyl ether and the formation of a thick brown- ish sludge that could not be further chemically charac- terized. It is doubtful that this mixture could have been injected intravenously, and likely that the exact length of heating and water content of the mixture were different when the patient and cousin prepared the concoction.

A human model for relapsing polychondritis was created inadvertently by an almost unbelievable at- tempt at recreational intravenous drug abuse. The symptoms mimicked the idiopathic disease and illus- trate that a direct biochemical insult can result in a similar syndrome.

ACKNOWLEDGMENT I would like to thank Dr. David Trentham for performing the assay for antibody to type II collagen, and Dr. Phil Cohen for his review of this manuscript.

REFERENCES 1. Michet CJ Jr, McKenna CH, Luthra HS, O’Fallon WM: Relapsing polychondritis. Survival and predictive role of early disease manifestations, Ann Intern Med 1986; 104: 74-78: 2. Estes SA: Relapsing polychondritis. A case report and literature review. Cutis 1983: 32: 471-474, 476. 3. McAdam LP. O’Hanlan MA. Bluestone A. Pearson CM: RelaDsina polvchondritis: prospective study of 23 patients and a review of the literature.Medicine (Balti- more) 1976; 55: 193-215. 4. Prieur DJ, Young DM, Counts DF: Auricular chondritis in fawn-hooded rats. A spontaneous disorder resembling that induced by immunization with type II colla- gen. Am J Pathol 1984; 116: 69-76. 5. Cremer MA, Pitcock JA, Stuart JM, Kang AH, Townes AS: Auricular chondritis in rats. An experimental model of relapsing polychondritis induced with type II colla- gen. J Exp Med 1981; 154: 535540. 6. McCune WJ, Schiller AL, Dynesius Trentham RA, Trentham DE: Type II collagen- induced auricular chondritis. Arthritis Rheum 1982; 25: 266-273. 7. Ebringer R. Rook G, Swana GT. Bottazzo GF, Doniach D: Autoantibodies to cartilage and type II collagen in relapsing polychondritis and other rheumatic diseases. Ann Rheum Dis 1981; 40: 473-479. 8. Foidart JM. Abe S. Martin GR. et at Antibodies to tvoe II collagen in relapsing polychondritis. N Engl J Med 1978; 299: 1203-1207.~’ - - 9. Trentham DE, Dynesius Trentham RA: Attenuation of an adjuvant arthritis by type II collagen. J immunology 1983; 139: 2689-2692 10. lsaak BL, Liesegang TJ, Michet CJ Jr: Ocular and systemic findings in relapsing polychondritis. Ophthalmology 1986; 93: 681-689. 11. Willis J, Atack EA, Kraag G: Relapsing polychondritis with multifocal neurologi- cal abnormalities. Can J Neurol Sci 1984; 11: 402-404. 12. Sundaram MB, Rajput AH: Nervous system complications of relapsing poly- chondritis. Neurology 1983; 33: 513-515. 13. Magargal LE, Donoso LA, Goldberg RE, Gonder J, Brodsky I: Ocular manifesta- tions of relapsing polychondritis. Retina 1981; 1: 96-99. 14. O’Hanlan M, McAdam LP, Bluestone R, Pearson CM: The arthropathy of re- lapsing polychondritis. Arthritis Rheum 1976; 19: 191-194. 15. Chang Miller A, Okamura M, Torres VE, et at Renal involvement in relapsing polychondritis. Medicine (Baltimore) 1987; 66: 202-217.

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