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Cutaneous foreign body granulomas associated with intravenous drug abuse
Cutaneous foreign body granulomas associated with intravenous drug abuse* Donald I. Posner, M.D.,** and Lieutenant Colonel Marshall A. Guill III, M C , USA*** Augusta and Fort Gordon, GA Intravenous drug abuse is a serious medical problem in the United States. We report a new cutaneous manifestation of drug abuse: the development of foreign body granulomas. These may develop months to years after the last intravenous injection and should be considered a possible cutaneous manifestation of systemic talc granulomatosis. (J AM ACADDERMATOL 13:869-872, 1985.)
Intravenous drug abuse is a serious medical problem of epidemic proportions in some areas of the United States. It is estimated that there are 450,000 to 600,000 opiate-dependent individuals currently living in the United States. ~.2During the 3-year period of 1980 to 1982, a total of 266 deaths occurred in the District of Columbia because of intravenous heroin use. 3 Most recently, physicians have noted the significant association of intravenous drug abuse and acquired immunodeficiency syndrome (AIDS). Approximately 17% of AIDS patients admit to previous intravenous drug use. 4 As dermatologists, we may see the cutaneous evidence of drug addiction. Needle tracks with scarring, subcutaneous abscesses, and venous thromboses are commonly seen and easily associated with intravenous drug abuse, s.6 Other skin manifestations include hyperpigmentation over veins, " s o o t " tattoos, urticaria¢ necrotic ulcers, From the Department of Dermatology, Medical College of Georgia, Augusta,** and the Dermatology Section, Dwight D. Eisenhower Army Medical Censer, Fort Gordon.*** Presented at the meeting of the Association of Military Dermatologists and at the Zola-Cooper Clinicopathologic Seminar in 1981. Reprint requests to: Dr. Donald I. Posner, Department of Dermatology, Medical College of Georgia, Augusta, GA 30912. *The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the view of the Department of the An-ny or the Department of Defense.
pigmented lesions of the tongue, palpable purpura as a result of leukocytoclastic vasculitis, and diffuse erythema with subsequent desquamation of the fingertips as a result of toxic shock syndrome?-~ All of these skin findings are temporally related to recent intravenous drug use. We report a new cutaneous manifestation of drug abuse, a case in which foreign body granulomas developed at the sites of intravenous injections of medication intended for oral use.
CASE REPORT A 22-year-old man presented to the Eisenhower Army Medical Center Dermatology Clinic, complaining of multiple, tender cutaneous nodules that had developed intermittently over the last 2 years. There was no family history of similar skin lesions. His general health was good, and a review of systems was negative. On physical examination, numerous firm nodules were noted over dorsal and ventral areas of his hand and arms (Figs. 1 to 3). These nodules were firm, movable, and did not appear to be attached to tendons. They ranged from 1 to 4 cm in diameter. They were located in close proximity to superficial veins. An excisional biopsy of one of the lesions was performed. Histologically, the nodule was located in the deep dermis. It was composed of adipose and fibrous connective tissue with interspersed bundles of epithelioid histiocytes and giant cells consistent with a foreign body granuloma. Polarized microscopy revealed diffuse birefringent crystals scattered throughout the granuloma
869
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Posner and Guill
Journal of the American Academy of Dermatology
Fig. 1. Two nodules on dorsum of right hand. Fig. 2. Large subcutaneous nodule on ventral surface of left wrist. Fig. 3. Numerous nodules on left forearm. Fig. 4. Granuloma formation in dermis with several large giant cells. (Hematoxylin-eosin stain; original magnification, x 52.) Fig. 5. Similar tissue as in Fig. 4, seen through polarized microscope. Birefringent crystals are scattered throughout granuloma.
Volume 13 Number 5, Part 2 November, 1985 (Figs. 4 and 5). X-ray spectrophotometer studies revealed this material to be composed of magnesium, silica, phosphorus, and chloride. These are materials found in talc. After the biopsy results were reviewed, the patient was questioned more closely and disclosed that he had abused multiple drugs, including heroin and amphetamines. He denied drug abuse since the onset of the first tender cutaneous nodule, some 2 years previously. Results of chest x-ray and pulmonary function tests were normal. Complete blood Count and results of automated blood chemistry studies were within normal limits. Since the patient was asymptomatic, further invasive studies to assess systemic involvement were not done. COMMENT Drug abuse in this case Was suspected because of the histopath0t0gic features of the tissue and was confirmedii~[yqater by.the patient. Many drug abusers, whether the abuse be of alcohol or intravenous drugs, can function relatively well in dayto-day living and try to hide their addiction from persons around them. It is interesting that our patient continued to develop new skin lesions up to 2 years after his last injection. The patient admitted to abuse of heroin, amphetamines, and other "recreational'.' drugs. The foreigri body granulomas were probably due to the abuse of amphetamines and other drugs in tablet form. Heroin arriving in the United States is relatively pure. However, before it reaches the user, it is " c u t " with many adulterants that resemble the pure powder both physically and in its solubilizing properties. This is necessary because heroin is administered either intravenously or subcutaneously by heroin addicts. 8 Some common heroin diluents include quinine, dextrose, lactose, mannito!, and baking soda? "s'~ These chemicals are not thought to cause foreign body granulomas. 12 Amphetamines and other oral drugs are usually packaged in tablet form for oral use but are frequently crushed and suspended in solution for intravenous injection by drug addicts. The tablets contain filler material to hold the tablet together. The principal filler is talc (hydrous magnesium silicate: Mg3 Si4 O1o (OH)z). ~3For example, pen-
Cutaneous foreign body granulomas 871
tazocine tablets (Talwin) are 75% talc by weight. 14 Other pharmaceuticals that are packaged in tablet form but are abused intravenously include methylphenidate (Ritalin), prop0xyphene (Darvon), methadone, morphine, and tripelennamine. ~5 We postulate that our patient extravasated suspended drug into his skin while attempting intravenous injection. This extravasated material led to foreign body granuloma s in the skin. "Skin popping," or subcutaneous inject!on, could also have PrOduced these lesions, although this method of abuse frequently leads to abscess formation: '8 However, our patient denied this form of drug injection. Intravenous injection of a suspension o f crushed tablets also leads to pulmonary talc granulomatosis. 13-t5Most of these patients complain of dyspnea. The foreign body granul0matous reactions produce pulmonary fibrosis, which leads to puimonary hypertension, right-sided heart failure, and even tleath in some individuals. ~SIn some patients with a long history of intravenous abuse, granulomas and minute talc crystals are not limited to the lungs but have been found i n the liver, spleen, bone marrow, and lymph nodes at autopsy: Larger crystals apparently become lodged in the lungs, whereas Smaller crystals m a y pass through the pulmonary vascular tree, either because the advanced pulmonary fibrosis and angiofibrosis lead to the formation of arteriovenous shunts or because a preexisting cardiac defect may allow fight-to-left shunting. The presence of talc crystals in the urine of these patients demonstrates that crystals can pass through the gl0merular filterl ~5 Typically there is a long interval between deposition of talc crystals and development of a gran 7 uloma. Because of this latency period, it may be as long as 40 to 50 years before the first granulorna appears. ~3It is known that large particles of silica do not Produce granulomas but that smaller particles, between 1 and 100 n m in the colloidal form, produce granulomas in all persons. The conversion of silica (i.e., sand) or silicates (i.e., talc) to this colloidal form may take many years, which could explain the delayed granuloma formation in our patient. It is important for dermatologists to be aware
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of all the Cutaneous manifestations of drug abuse because of the benefits of early diagnosis and therapeutic intervention. Cutaneous foreign body granulomas m a y be a more c o m m o n manifestation than is realized ., since in the past these lesions m a y have been simply passed over as benign cysts. Since systemic talc-induced granulomatosis is potentially lethal, it is important to identify persons at risk. Cutaneous talc granulomas in drug abusers m a y be an important cutaneous manifestation of systemic illness. REFERENCES 1. Hollister LE: Drug abuse in the United State~: The past decade. Drug Alcohol Depend 11:49-53, 1983. 2. U.S. Bureau of the Census: Statistical Abstract of the United States: 1984, ed. 104. Washington, D.C., 1983, the Bureau. 3. Centers for Disease Control: Heroin: Related deaths-District of Columbia, 1980-1982. MMWR 32:321-324, 1983. 4. Centers for Disease Control: Update: Acquired immunodeficiency syndrome (AIDS)--United States, MMWR 32:688-69 I, 1984. 5. Young AW, Rosenberg FR: Cutaneous stigmas of heroin addiction. Arch Dermatol 104:80-86, 1971.
Journal of the American Academy of Dermatology
6. VollumDI: Skin lesions in drug addicts. Br Med J 2:647650, 1970. 7. Minkin W, Cohen HI: Dermatologic complications of heroin addiction. N Engl J Meal 277:473-475, 1967, 8. White WB, Barrett S: Penile ulcer in heroin abuse: A case report. Cutis 29:62-63, 69, 1982. 9. Westerhof W, Wolters EC, Brookbakker JTW, et ah Pigmented lesions of the tongue in heroin addicts: Fixed drug eruption. Br J Dermatol 109:605-610, 1983. i0. Gendelman H, Linzer M, Barland P, Bezahler GH: Leukocytoclastic vasculitis in an intravenous heroin abuser. NY State J Med 83:984-986, 1983. 11. Chapman RL, Colville JM, Lauter CB: Toxic-shock syndrome related to intravenous heroin use. N Engl J Med 307:820-821, 1982. 12. Hirsh BC, Johnson WC: Concepts of granulomatous inflammation. Int J Dermatol 23:90-100, 1984. 13. Pucevich MV, Rosenberg EW, Bale GF, Terzakis JA: Widespread foreign-body granulomas and elevated serum angiotensin-converting enzyme. Arch Dermatol 119: 229-234, 1983. 14. Farber HW, Fairman RP, Glauser FL: Talc granulomatosis: Laboratory findings similar to sarcoidosis. Am Rev Respir Dis 125:258-261, 1982. 15. Mariani-Costantini R, Jannotta FS, Johnson FB: Systemic visceral talc granulomatosis associated with miliary tuberculosis in a drug addict. Am J Clin Pathol 78:785789, 1982.
Intravenous drug abuse is a serious medical problem of epidemic proportions in some areas of the United States. It is estimated that there are 450,000 to 600,000 opiate-dependent individuals currently living in the United States. ~.2During the 3-year period of 1980 to 1982, a total of 266 deaths occurred in the District of Columbia because of intravenous heroin use. 3 Most recently, physicians have noted the significant association of intravenous drug abuse and acquired immunodeficiency syndrome (AIDS). Approximately 17% of AIDS patients admit to previous intravenous drug use. 4 As dermatologists, we may see the cutaneous evidence of drug addiction. Needle tracks with scarring, subcutaneous abscesses, and venous thromboses are commonly seen and easily associated with intravenous drug abuse, s.6 Other skin manifestations include hyperpigmentation over veins, " s o o t " tattoos, urticaria¢ necrotic ulcers, From the Department of Dermatology, Medical College of Georgia, Augusta,** and the Dermatology Section, Dwight D. Eisenhower Army Medical Censer, Fort Gordon.*** Presented at the meeting of the Association of Military Dermatologists and at the Zola-Cooper Clinicopathologic Seminar in 1981. Reprint requests to: Dr. Donald I. Posner, Department of Dermatology, Medical College of Georgia, Augusta, GA 30912. *The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the view of the Department of the An-ny or the Department of Defense.
pigmented lesions of the tongue, palpable purpura as a result of leukocytoclastic vasculitis, and diffuse erythema with subsequent desquamation of the fingertips as a result of toxic shock syndrome?-~ All of these skin findings are temporally related to recent intravenous drug use. We report a new cutaneous manifestation of drug abuse, a case in which foreign body granulomas developed at the sites of intravenous injections of medication intended for oral use.
CASE REPORT A 22-year-old man presented to the Eisenhower Army Medical Center Dermatology Clinic, complaining of multiple, tender cutaneous nodules that had developed intermittently over the last 2 years. There was no family history of similar skin lesions. His general health was good, and a review of systems was negative. On physical examination, numerous firm nodules were noted over dorsal and ventral areas of his hand and arms (Figs. 1 to 3). These nodules were firm, movable, and did not appear to be attached to tendons. They ranged from 1 to 4 cm in diameter. They were located in close proximity to superficial veins. An excisional biopsy of one of the lesions was performed. Histologically, the nodule was located in the deep dermis. It was composed of adipose and fibrous connective tissue with interspersed bundles of epithelioid histiocytes and giant cells consistent with a foreign body granuloma. Polarized microscopy revealed diffuse birefringent crystals scattered throughout the granuloma
869
870
Posner and Guill
Journal of the American Academy of Dermatology
Fig. 1. Two nodules on dorsum of right hand. Fig. 2. Large subcutaneous nodule on ventral surface of left wrist. Fig. 3. Numerous nodules on left forearm. Fig. 4. Granuloma formation in dermis with several large giant cells. (Hematoxylin-eosin stain; original magnification, x 52.) Fig. 5. Similar tissue as in Fig. 4, seen through polarized microscope. Birefringent crystals are scattered throughout granuloma.
Volume 13 Number 5, Part 2 November, 1985 (Figs. 4 and 5). X-ray spectrophotometer studies revealed this material to be composed of magnesium, silica, phosphorus, and chloride. These are materials found in talc. After the biopsy results were reviewed, the patient was questioned more closely and disclosed that he had abused multiple drugs, including heroin and amphetamines. He denied drug abuse since the onset of the first tender cutaneous nodule, some 2 years previously. Results of chest x-ray and pulmonary function tests were normal. Complete blood Count and results of automated blood chemistry studies were within normal limits. Since the patient was asymptomatic, further invasive studies to assess systemic involvement were not done. COMMENT Drug abuse in this case Was suspected because of the histopath0t0gic features of the tissue and was confirmedii~[yqater by.the patient. Many drug abusers, whether the abuse be of alcohol or intravenous drugs, can function relatively well in dayto-day living and try to hide their addiction from persons around them. It is interesting that our patient continued to develop new skin lesions up to 2 years after his last injection. The patient admitted to abuse of heroin, amphetamines, and other "recreational'.' drugs. The foreigri body granulomas were probably due to the abuse of amphetamines and other drugs in tablet form. Heroin arriving in the United States is relatively pure. However, before it reaches the user, it is " c u t " with many adulterants that resemble the pure powder both physically and in its solubilizing properties. This is necessary because heroin is administered either intravenously or subcutaneously by heroin addicts. 8 Some common heroin diluents include quinine, dextrose, lactose, mannito!, and baking soda? "s'~ These chemicals are not thought to cause foreign body granulomas. 12 Amphetamines and other oral drugs are usually packaged in tablet form for oral use but are frequently crushed and suspended in solution for intravenous injection by drug addicts. The tablets contain filler material to hold the tablet together. The principal filler is talc (hydrous magnesium silicate: Mg3 Si4 O1o (OH)z). ~3For example, pen-
Cutaneous foreign body granulomas 871
tazocine tablets (Talwin) are 75% talc by weight. 14 Other pharmaceuticals that are packaged in tablet form but are abused intravenously include methylphenidate (Ritalin), prop0xyphene (Darvon), methadone, morphine, and tripelennamine. ~5 We postulate that our patient extravasated suspended drug into his skin while attempting intravenous injection. This extravasated material led to foreign body granuloma s in the skin. "Skin popping," or subcutaneous inject!on, could also have PrOduced these lesions, although this method of abuse frequently leads to abscess formation: '8 However, our patient denied this form of drug injection. Intravenous injection of a suspension o f crushed tablets also leads to pulmonary talc granulomatosis. 13-t5Most of these patients complain of dyspnea. The foreign body granul0matous reactions produce pulmonary fibrosis, which leads to puimonary hypertension, right-sided heart failure, and even tleath in some individuals. ~SIn some patients with a long history of intravenous abuse, granulomas and minute talc crystals are not limited to the lungs but have been found i n the liver, spleen, bone marrow, and lymph nodes at autopsy: Larger crystals apparently become lodged in the lungs, whereas Smaller crystals m a y pass through the pulmonary vascular tree, either because the advanced pulmonary fibrosis and angiofibrosis lead to the formation of arteriovenous shunts or because a preexisting cardiac defect may allow fight-to-left shunting. The presence of talc crystals in the urine of these patients demonstrates that crystals can pass through the gl0merular filterl ~5 Typically there is a long interval between deposition of talc crystals and development of a gran 7 uloma. Because of this latency period, it may be as long as 40 to 50 years before the first granulorna appears. ~3It is known that large particles of silica do not Produce granulomas but that smaller particles, between 1 and 100 n m in the colloidal form, produce granulomas in all persons. The conversion of silica (i.e., sand) or silicates (i.e., talc) to this colloidal form may take many years, which could explain the delayed granuloma formation in our patient. It is important for dermatologists to be aware
872
Posner and Guill
of all the Cutaneous manifestations of drug abuse because of the benefits of early diagnosis and therapeutic intervention. Cutaneous foreign body granulomas m a y be a more c o m m o n manifestation than is realized ., since in the past these lesions m a y have been simply passed over as benign cysts. Since systemic talc-induced granulomatosis is potentially lethal, it is important to identify persons at risk. Cutaneous talc granulomas in drug abusers m a y be an important cutaneous manifestation of systemic illness. REFERENCES 1. Hollister LE: Drug abuse in the United State~: The past decade. Drug Alcohol Depend 11:49-53, 1983. 2. U.S. Bureau of the Census: Statistical Abstract of the United States: 1984, ed. 104. Washington, D.C., 1983, the Bureau. 3. Centers for Disease Control: Heroin: Related deaths-District of Columbia, 1980-1982. MMWR 32:321-324, 1983. 4. Centers for Disease Control: Update: Acquired immunodeficiency syndrome (AIDS)--United States, MMWR 32:688-69 I, 1984. 5. Young AW, Rosenberg FR: Cutaneous stigmas of heroin addiction. Arch Dermatol 104:80-86, 1971.
Journal of the American Academy of Dermatology
6. VollumDI: Skin lesions in drug addicts. Br Med J 2:647650, 1970. 7. Minkin W, Cohen HI: Dermatologic complications of heroin addiction. N Engl J Meal 277:473-475, 1967, 8. White WB, Barrett S: Penile ulcer in heroin abuse: A case report. Cutis 29:62-63, 69, 1982. 9. Westerhof W, Wolters EC, Brookbakker JTW, et ah Pigmented lesions of the tongue in heroin addicts: Fixed drug eruption. Br J Dermatol 109:605-610, 1983. i0. Gendelman H, Linzer M, Barland P, Bezahler GH: Leukocytoclastic vasculitis in an intravenous heroin abuser. NY State J Med 83:984-986, 1983. 11. Chapman RL, Colville JM, Lauter CB: Toxic-shock syndrome related to intravenous heroin use. N Engl J Med 307:820-821, 1982. 12. Hirsh BC, Johnson WC: Concepts of granulomatous inflammation. Int J Dermatol 23:90-100, 1984. 13. Pucevich MV, Rosenberg EW, Bale GF, Terzakis JA: Widespread foreign-body granulomas and elevated serum angiotensin-converting enzyme. Arch Dermatol 119: 229-234, 1983. 14. Farber HW, Fairman RP, Glauser FL: Talc granulomatosis: Laboratory findings similar to sarcoidosis. Am Rev Respir Dis 125:258-261, 1982. 15. Mariani-Costantini R, Jannotta FS, Johnson FB: Systemic visceral talc granulomatosis associated with miliary tuberculosis in a drug addict. Am J Clin Pathol 78:785789, 1982.