J Am Board Fam Pract: first published as 10.3122/jabfm.5.1.85 on 1 January 1992. Downloaded from Recurrent Leg : Pathogenesis, Tre.atment, And Prevention

Roben P. Pierce, M.D., and Allen]. Daugird, M.D.

Recurrent cellulitis can develop in a variety of therapy. Subsequently, she developed chronic bi­ settings. Recurrent febrile episodes associated lateral lower leg before her first hospital­ with arm or leg infections, sometimes described ization at our institution. as erysipelatous, have been noted for years to Upon admission, she denied fever, chills, nau­ occur in the setting of filarial, postoperative, or sea, vomiting, shortness of breath, or chest pain. idiopathic chronic . I More recently, She reported bilateral tubal ligation and ovarian recurrent cellulitis has been described as a late cyst removal more than 20 years ago. Five years complication of coronary artery bypass venec­ ago she had a radical mastectomy for adenocarci­ tomy,2-8 pelvic surgery, such as vulvectomy with noma of the breast but had negative lymph nodes lymphadenectomy9 or hysterectomy with lym­ and underwent no further treatment. There was ph adenectomy, 10 or of pelvic irradiation after hys­ no history of cellulitis of the right arm after the terectomy.11,12 The cause of recurrent cellulitis mastectomy. She denied any other pelvic surgery, has not been precisely defined but appears to be leg surgery, or abdominal or pelvic irradiation. multifactorial, involving mechanical, infectious, On examination, her temperature was 37.4°C and immune-mediated factors. We present a case (99.32°F), blood pressure 144/84 mmHg, pulse 80 of a woman with recurrent cellulitis of the legs beats per minute, and respirations 24/minute. She and briefly review the literature concerning the was an obese woman in no acute distress. Her pathogenesis, treatment, and prevention of this head, eyes, ears, throat, heart, lungs, and abdo­ perplexing problem. men were normal. There was pitting edema (3+) in the legs bilaterally and marked erythema, Case Report warmth, and tenderness of the right calf. The A 78-year-old obese, hypertensive woman was circumference 15 em below the patella measured admitted to the hospital after 2l;2 days of redness, 54 em on the right, 38 em on the left. There were swelling, and pain in the right leg. She reported a no vesicles, bullae, ulcers, or erythematous http://www.jabfm.org/ history of "phlebitis" in her legs in the distant streaks. Absent were any fissures, maceration, or past. Fifteen years before admission to our hospi­ other changes suggestive of tinea pedis. The tal, she was admitted to another facility with white cell count wa's 13.8 X 109/L (13,800/mm3) swelling, pain, eczematous changes, and blebs of with a differential showing 0.83 segmented neu­ the left leg. She was discharged 1 month later, her trophils and 0.05 band forms.

condition diagnosed as "cellulitis superimposed She was given and cefawlin intra­ on 28 September 2021 by guest. Protected copyright. over old postphlebitic leg." Six: years before ad­ venously. A venogram showed no deep venous mission to our hospital she was again treated for but was suggestive of previous throm­ cellulitis, this time in the right leg. Streaking bophlebitis involving the lesser saphenous and suggestive oflymphangitis, redness, small blisters, anterior tibial veins with multiple incompetent and right lower extremity edema (2 to 3 +) were communicators. On the 2nd hospital day, the noted at the time of that admission. She devel­ patient's temperature rose to 38.7°C (101.7°F), oped bullous lesions during the hospitaliza­ but her fever quickly dropped, and she remained tion, but she gradually improved with antibiotic afebrile for the remainder of the hospitalization. The leg redness and warmth gradually resolved but the edema remained. She was discharged on Submitted, revised, 13 August 1991. From the Department of Family and Community Medicine, the 8th hospital day to complete an additional University of Missouri, Columbia. Address reprint requests to week of oral cephalexin therapy. Roben P. Pierce, M.D., MAl03 Medical Sciences Building, Uni­ Sixteen weeks later she had the first of five versity of Missouri Hospital and Clinics, One Hospital Drive, Columbia,MO 65212. readmissions for cellulitis of the legs. These hos-

Recurrent Leg Cellulitis 85 J Am Board Fam Pract: first published as 10.3122/jabfm.5.1.85 on 1 January 1992. Downloaded from

pitalizations occurred during the next 15 months. seven reports of more than 80 episodes of celluli­ Four of the episodes occurred in the right leg, one tis in 31 venectomy patients, cultures were ob­ in the left. The interval between episodes tained during acute episodes from skin 6 times averaged 11 weeks (range 6 to 18 weeks). Her and from blood 28 times.2,8 Only 7 times were symptoms typically appeared during a 2 -day time pathogens isolated, 3 times from skin and 4 times period. On two occasions she had symptoms sug­ from blood.2,6 When a causative organism is iso­ gesting systemic toxicity. Her temperature upon lated from tissue, it is most often nongroup A admission averaged 38.6°C (l01.5°F) (range (3-hemolytic streptococcus (groups B, C, and 37.6°C [99.7°F] to 39.8°C [103.6°F)), and leuko­ G).2,9,1l,12 Staphylococcus has also been im­ cyte counts averaged 11.4 X I09JL (11,400/mm3) plicated, though to a much lesser degree.l,s In (range 7.1 to 14.5 X 1Q9JL). A left shift was gener­ many instances, no portal of entry for these ally present. Tinea pedis was noted on only one pathogens is identified. In other cases, breaks in hospitalization. At that time, topical miconazole the skin barrier resulting from dermatophytosis cream was applied, and her dermatophytosis may be the portal of entry, as tinea pedis infec­ resolved. Treatment with the topical antifun­ tions have been found in a significant number of gal agent was continued daily, but she none­ patients with recurrent cellulitis.2,s,6,14 theless developed recurrent cellulitis 6 weeks There is indirect evidence that host immune later. Attempts to reduce her chronic edema responses also playa role in the development of mechanically with compression stockings were some patients' recurrent cellulitis. There are case also unsuccessful. reports of patients with recurrent cellulitis who After the sixth hospitalization she was pre­ improve without antimicrobial therapy.3,9 Older scribed a prophylactic daily oral dose of 1 g of reports describe immediate local reactions to in­ penicillin V potassium. Although her marked leg tradermal injection of trichophytin extract in pa­ edema has remained unchanged, she has had no tients with recurrent erysipelas-like reactions and recurrences of cellulitis in 48 weeks of treatment. fungal infections of the feet. 14,IS The role of tinea pedis therefore may not only be to provide a Discussion portal of entry for streptococcal or other organ­ The role of impaired venous drainage in the isms through breaks in the skin, but also to pathogenesis of recurrent cellulitis is suggested by stimulate a dermatophytid immune response. Im­ the presence of the disease in patients who have mune responses to bacterial exotoxins have been had saphoneous venectomy during coronary ar­ implicated in the pathogenesis of recurrent cellu­ http://www.jabfm.org/ tery bypass grafting.3,4 Impaired lymphatic drain­ litis as well. Older reports describe patients with age may be even more important in the pathogen­ recurrent erysipelas who develop an erysipelas­ esis of recurrent cellulitis, as the protein-rich like reaction in the area of their recurrences fol­ lymphatic fluid serves as an excellent culture me­ lowing the injection of sterile streptococcal fil­ dium for bacteria. Mechanical disruption of lym­ trates at a distant site. 16 In more recent animal

phatic flow from lymph node resections or radia­ studies, streptococcal exotoxins produced ery­ on 28 September 2021 by guest. Protected copyright. tion therapy may be the process that increases the thematous, edematous skin reactions once an ani­ likelihood of recurrent cellulitis after these pro­ mal was sensitized,17 Furthermore, streptococcal cedures. Filarial processes destroy lymphatic exotoxin appears to enhance hypersensitivity re­ channels and increase likelihood of cellulitis epi­ action to other antigens, such as PPD,17 leading sodes,l3 Although less well described, bacterial one author to speculate that the pathogenesis of processes, such as a single episode of cellulitis or recurrent cellulitis may involve streptococcal exo­ lymphangitis, may destroy lymphatic channels toxin-enhanced hypersensitivity to fungal anti­ through direct toxic effects. The subsequent dis­ gens.2 Finally there is indirect evidence that im­ ruption of normal lymphatic flow may predispose paired vascular drainage can result in increased some patients, such as the one we describe, with­ local concentrations of allergen to which a host out surgical risk factors or a history of radiation, may be sensitized, increasing the allergic response to recurrent cellulitis. 3,13 in the area of poor drainage.18 Bacterial pathogens in patients with recurrent The clinical manifestations described in each of cellulitis have proved difficult to recover.4,IO In the various series of recurrent cellulitis are simi-

86 JABFP Jan.-Feb.1992 Vol. 5 No.1 J Am Board Fam Pract: first published as 10.3122/jabfm.5.1.85 on 1 January 1992. Downloaded from lar. Chronic lymphedema is not always present, 3. Idem. Recurrent cellulitis after saphenous venectOmy but there is typically some evidence or history for coronary bypass surgery. Ann Intern Med 1982; 97:493-6. of venous or lymphatic compromise. Patients 4. Idem. Non-group A beta-hemolytic streptococcal generally present with high fever, systemic toxic­ cellulitis: association with venous and lymphatic ity, and leukocytosis. Although not seen in our compromise. AmJ Med 1985; 79:155-9. patient, there can be a delay of up to 24 hours 5. Hurwitz RM, TIsserand ME. Streptococcal cellulitis before the arm or leg shows typical findings of proved by skin biopsy in a coronary artery bypass graft patient. Arch Dermato11985; 121:908-9. cellulitis.8,9 Local erythema can start in the area of 6. Greenberg J, DeSanctis RW, Mills RM Jr. Vein­ a preexisting extremity or abdominal surgical scar, donor-leg cellulitis after coronary artery bypass sur­ or the erythema, as in this case, can arise without gery. Ann Intern Med 1982; 97:565-6. any other preceding skin lesions. The extremity 7. File TMJr, TanJS, Maseelall EA, Snyder RO. Re­ generally has erythema, swelling, and tenderness current cellulitis after bypass surgery associated with typical of any cellulitis, but some authors have psoriasis pener].JAMA 1984; 252:1681. noted a uniquely fat, irregular, nonindurated 8. Copeland RB, Simpson MT. Recurrent cellulitis: a 2 late complication of coronary artery bypass surgery. and well-demarcated border to the erythema. ,12 J MedAssocGa 1985; 74:325-6. Most series do not report any subsequent 9. BoumaJ, DankertJ. Recurrent acute leg cellulitis in desquamation. patients after radical vulvectomy. Gynecol Oncol The treatment of an acute attack of recurrent 1988; 29:50-7. cellulitis is essentially that of any cellulitis. Once 10. Dankert J, Bouma J. Recurrent acute leg cellulitis after hysterectomy with pelvic lymphadenectomy. Br the recurrent pattern is recognized and the acute J Obstet Gynaeco11987; 94:788-90. episode is controlled, treatment is directed at cel­ 11. Binnick AN, Klein RB, Baughman RD. Recurrent lulitis prevention. In several reports,2,5,6 control of erysipelas caused by group B streptococcus organ­ patients' tinea pedis resulted in control of their isms. Arch Dermato11980; 116:798-9. cellulitis recurrences. Our patient had clinically 12. Chmel H, Hamdy M. Recurrent streptococcal cellu­ litis complicating radical hysterectomy and radiation evident tinea pedis on only one occasion, how­ therapy. Obstet Gynecoll984; 63:862-4. ever, and its control did not prevent recurrence of 13. Marsden PD. Lymphoreticular filariasis. In: her disease. Penicillin did yield clinical improve­ Hoeprich PD, editor. Infectious diseases. 3rd ed. ment in our patient. When given orally or as a Philadelphia: Harper & Row, 1983:1282-5. monthly injection, penicillin has been shown in 14. Sulzberger MB, Rostenberg AJr, Goetze D. Recur­ rent erysipelas-like manifestations of the legs.JAMA

one other case report and in two case series to be http://www.jabfm.org/ 9 11 1937; 108:2189-93. effective in preventing disease recurrences - 15. Traub EF, Tolmach JA. An erysipelas-like eruption and, therefore, should be considered in patients complicating dermatophytosis. JAMA 1937; 108: with recurrent leg cellulitis. 2187-9. 16. Birkhaug KE. Erysipelas: VIII. Bacterial allergy to Streptococcus erysipeliltous in recurrent erysipelas. References JAMA 1928; 90:1997-2001. 17. Schlievert PM, Bettin KM, Watson DW. Reinter­ 1. Edwards EA. Recurrent febrile episodes and on 28 September 2021 by guest. Protected copyright. lymphedema.JAMA 1963; 184:858-62. pretation of the Dick test: role of group A strepto­ 2. Baddour LM, Bisno AL. Recurrent cellulitis after coccal pyrogenic exotoxin. Infect Immunol 1979; coronary bypass surgery: association with superficial 26:467-72. fungal infection in saphenous venectomy limbs. lB. Naide M. Allergic lesions following thrombophlebi­ JAMA 1984; 251:1049-52. tis. Arch Intern Med 1947; 80:388-96.

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