Case repo rt Eruptive xanthomas in hyperlipoproteinemia Eruptive xanthomos as reveo,ling sign qf type r hyperlipoproteinemia in a patient with a p.rrchotic cfY/ldrome E. Sordi, M. Concetta Fargnoli, O. Sordi and K. Peris SUMMARY We describe a 33-year-old man affected with a psychotic syndrome, who developed eruptive xantho- mas on the knees, elbows, buttocks and neck. In addition, diabetes mellitus, obesity and alcohol abuse but no family history of hyperlipidemia could be identified, suggesting the diagnosis of type V pattern of hyperlipoproteinemia. Complete regression of cutaneous lesions was observed 12 weeks after di- etary restrictions and medica! management of diabetes. Six months after disappearance of eruptive xanthomas, the patient is still under treatment and no recurrence has been observed. Introduction Xanthomas are localized deposits oflipids in the skin and more rarely in the subcutaneous tissue, which are frequently associated w itl1 disturbances of lipoprotein metabolism (1). Metabolic lipoprotein abnormalities may be seen as manifestation of specific genetic disor- ders (prima1y hyperlipoproteinemias) or as an associ- ated phenomenon secondary to an underlying disease such as diabetes melli tus, hypothyroidism, primary bil- iaty cirrhosis, nephrotic syndrome and pancreatitis (sec- onda1y hyperlipoproteinemias). Xanthomas have been clinically classified as tendi- nous, emptive, tuberous , planar and generalized on the basis of anatomic distribution and mode of develop- ment (1). Eruptive xanthomas occur mainly in tl1e set- ting of severe hypertriglyceridemia , high semm con- centrations of chylomicrons and/ or very low density lipoproteins (VLDL) and contain greater amounts of trig- lycerides than other types of xanthomas. They appear as pin-head or larger yellowish papules, with a slightly erythematous base, preferentially located over pres- sure sites such as extensor surfaces of the upper and lower extremities and buttocks _(2). They are not rarely . associated with pruritus. Histologic features of eruptive xanthomas include a dermal infiltrate composed of his- tiocytes with foamy cytoplasm admixed with neutro- phils, mononuclear cells and sometimes multinucleated giant cells. We describe a 33-year-old patient affected with a psychotic disorder who developed eruptive xantho- mas caused by a severe hypertriglyceridemia second- ary to diabetes mellitus; obesity and alcohol abuse were also noted. Complete regression of cutaneous lesions was observed after dietary restrictions and medica! man- agement of diabetes. Acta Dermatoven APA Vol 11, 2002, No 1 ------------- - - - -2.J Eruptive xanthomas in hyperlipoproteinemia Figure 1. Eruptive xanthomas over the buttocks (a); complete regression of cutaneous lesions after dietary restrictions and medical management of diabetes (b). Case report A 33-year old male was examined for a disseminated, asymptomatic papular eruption, which had appeared in crops over the previous 5 months (Fig. la). His medica! history included a psychotic disorder fulfilling DSM IV cri- teria for schizophrenia and has been treated since the age of 23 with chlorpromazine hydrochloride (50 mg/ day). The patient was alcoholic and a heavy smoker. Family history was negative for meta bo lic and psychiatric disor- clers . Physical examination revealed obesity with hun- dreds of pink to yellowish, soft papules located over the buttocks, knees, elbows and neck. Hepatomegaly was also expressed. Laboratory findings inclucled a grossly lipernic serum with markedly elevated serum levels of triglycerides 3248 mg/ dl (n.v.: 50-200 mg/dl) , choles- terol 609 mg/dl (n.v.: 50-200 mg/dl), serum glucose 328 mg/dl (n.v.: 70-110 mg/dl) and ALT levels 61 U/I (n.v.: 0- 40 U/ I). Serum lipoprotein electrophoresis showed a marked increase in chylomicrons and in the leve[ ofVLDL 700 mg/dl (n.v.: up to 40 mg/cll) as well as a decrease in high-density lipoprotein leve) (HDL) 23 ,7 mg/dl (n.v.: 35-120 mg/ dl). Increase of apo-lipoprotein-B levels 264 mg/ dl (n.v.: 55-135 mg/cll) was also observed. The analy- sis of urine disclosed 3+ glucose, 1 + protein, 1 + hemoglo- bin and 1 + ketonic compound. In addition, by ophthal- mologic examination lipemia retinalis was detected and by ultrasonography hepatic steatosis. Histopathologic examination of the skin biopsy specimen from the but- tock showed a mixed clermal inflammatory infiltrate com- posed of numerous, large foamy cells surrounded by lym- phocytes and histiocytes (Fig. 2). A multidisciplina1y approach including the psychia- trists and the cliabetologists was introduced. The pa- cient was treated with insulin 5 to 20 IU/ day and a hypo caloric diet in addition to 50 mg/day of chlorpromazine hydrochloride. Improvement of cutaneous lesions was observecl after 5 weeks of combinecl treatment, and complete regression was achieved within 12 weeks (Fig. lb). Serum levels of triglycerides and cholesterol significantly clecreased after 4 weeks of treatment and a reduction of hepatic steatosis was detectecl by ultra- sonography after 12 weeks. The patient is currently under treatment including dieta1y rescrictions and 5 IU/ day of insulin, no recurrence of cutaneous lesions has been observed twelve months after clearing. Figure 2. "Foamy cells" admixed with an inflam- matory infiltrate in the superficial dermis (Hemato- xylin-Eosin stain; original magnification x250). Case repo rt 26 Acta Dermatoven APA Vol 11, 2002, No 1 Case repo rt Discussion Eruptive xanthomas are frequently observed in the hypertriglyceridemic syndromes such as type I and V primary hyperlipoproteinemias (1-3). Type I primary hyperlipoproteinemia is an autosomal recessive dis- ease, occurring at an early age, and is caused by an impaired lipoprotein lipase activity with defective se- rum removal of chylomicrons, resulting in severe hyper- chylomicronemia. In type V hyperlipoproteinemia, the dual defect in triglycerides metabolism, overproduc- tion of VLDL and defective removal of triglycerides- rich lipoproteins, results in a combined elevation of chy- lomicron and VLDL levels. In addition to eruptive xan- thomas, of a marked hyperchylomicronemia can include abdominal pain associated with acute pancreatitis , hepatosplenomegaly and lipemia retinalis. Eruptive xanthomas have been rarely observed in patients with type IV primary hyperlipoproteinemia characterized by an accelerated hepatic production ofVLDL. Finally, eruptive xanthomas have been reported in patients with acquired forms ofhypertriglyceridemia secondary to uncontrolled diabetes mellitus, nephrotic syndrome, alcohol and drug abuse (estrogens, corticosteroids and 13-cis retinoic acid) at sites of a prior injury (1 , 4-7). In our patient diabetes mellitus and obesity in addition to alcohol abuse suggested the diagnosis of seconda1y hypertriglyceridemia. Anamnestic data and serum lipid levels of other members of the patient's family excluded a familial occurrence. There is growing evidence that insulin deficiency and/ or resistance associated w ith un- 17 1"FE• R E i'\ T r, E. i;:, l. ."!.t . . . ..,/ . . t . . JJ.' t..,1 _:..; 1...:) Eruptive xanthomas in hyperlipnproteinemia controlled diabetes and insulin resistance secondary to obesity can induce hepatic overproduction ofVLDL as well asa defective lipolysis ofVLDL and chylomicrons. In addition , ethanol ingestion by stimulating VLDL trig- lycerides !iver production further accentuates the lipemia (1). Treatment of eruptive xanthomas consists of dietary restrictions and anti-hyperlipidemic drugs (8). In our patient, insulin administration in addition to diet and weight reduction induced complete regression of cuta- neous lesions. In 1994, Sartori et al. described a similar case of a 32-year-old patient affected by psychosis, who developed eruptive xanthomas in the presence of type V hyperlipoproteinemia (9). In contrast to our patient a regression of cutaneous lesions was not achieved due to the low patient's compliance to therapy (9). Conclusion Eruptive xanthomas can occur in primary and sec- ondary hyperlipoproteinemias, therefore a careful per- sonal and family history as well as laboratory investiga- tions are recommended in order to detect an underly- ing metabolic disorders . Acknowledgements The Authors wish to thank Pasquale Antignani, MD, De- pa1tment of Psychiatric.~, and Giuseppe Campagna, MD, Department ofintemal Medicine, Frosinone Hospital, Italy, for helping in the clinical management of the patient. l. Parker F. Xanthomas and hyperlipidemias. J Am Acad Dermatol 1985; 13: 1-30. AUTHORS' ADDRESSES 2. Cruz PD, East C, Bergstresser PR. Dermal, subcutaneous, and tendon xanthomas: diagnostic markers for specific lipoprotein disorders. J Am Acad Dermatol 1988; 19: 95-111. 3. Fredrickson DS, Levy RI , Lees RS. Fat transport in lipoproteins - an integrated approach to mecha- nisms and disorders. N Engl J Med 1967; 276: 32-42, 94-103, 148-56, 215-25, 273-81. 4. Teltscher J, Silverman RA, StorkJ. Eruptive xanthomas in a child with the nephrotic syndrome. J Am Acad Dermatol 1989; 21: 1147-9. ' 5. Dicken CH, Connolly SM. Eruptive xanthomas associated with isotretinoin (13-cis-retinoic acid) . Arch Dermatol 1980; 116: 951-2. 6. Roederer G, Xhignesse M, Davignon J. Eruptive and tubero-eruptive xanthomas of the skin arising on sites of prior injury. JAMA 1988; 260: 1282-3. 7. Miwa N, Kanzaki T. The Koebner phenomenon in eruptive xanthoma. j Dermatol 1992; 19: 48-50. 8. Crowe MJ, Gross DJ. Eruptive xanthoma. Cutis 1992; 50: 31-2. 9. Sartori P, Stinco G, Trevisan G. Xantomatosi eruttiva in un paziente psicotico con iperlipoproteinemia di lipo V. G Ital Dermatol Venereol 1994; 129: 433-6. Emiliano Sordi, MD, Department of Dermatology, University ofl'Aquila, Via Vetoio-Coppito 2, 6 7100 l'Aquila, Italy ConcettaFargnoli, MD, same address Ketty Peris, MD, same address - corr. author, e-mail: telederm @univaq.it Greste So rdi, MD, Department oj Dermatology, Ospedale Civile di Frosinone, Viale Mazzini, 03100 Frosinone, Italy Acta Dermatoven APA Vol 11, 2002, No 1 - --- --- - -------- - - - - - - 27