Volume 27 Number 3 September 1992
Correspondence 487
In 1985 I wrote a letter to the Editor ofthis JOURNAL about "Erythema chronicum migrans: Afzelius and Lipschiitz,"\ referring to an article by Schorr et al. 2 In turn, Dr. Alfred Hollander commented on my remarks. 3 In my letter I reported a tick bite and subsequent erythema chronicum migrans in myself, from August 1984. Checking the old calendars, I found that the tick bite and erythema must have occurred between Aug. 14 and Sept. 16, 1984. Admittedly, the remote possibility of coming into the country with both tick and (dormant) disease on Aug. 14,1984 cannot be ruled out with certainty. Given my daily routine of cycling into the Judean Hills and subsequent showering makes it unlikely that a tick bite in the groin would have escaped my attention more than one day or two. (This location had prevented me from photographically documenting the case.) As stated in my letter, \ the eruption cleared after penicillin. No histopathologic examination or Borrelia serology was done. A recent check for unrelated reasons did not reveal any antibodies to Borrelia burgdorferi. Consequently there is no confirmation of my self-diagnosis. On the other hand, the history, the tick bite (the tick being removed by myself), the characteristic clinical appearance of the erythema chronicum migrans anc,i the prompt response to penicillin favor the original diagnosis. Thus there might have been a case of Lyme disease before the "first case" as reported by Abraham et al.
Karl Holubar, MD Department of the History of Medicine Wahringer Strasse 25 A-I090 Vienna, Austria
REFERENCES 1. Holubar K. Erythema chronicum migrans: Afzelius and LipschUtz [Letter]. JAM ACAD DERMATOL 1985;13:663-4. 2. Schorr WF, Tauschek AL, Dickson KB, et al. Eosinophilic cellulitis (Wells' syndrome): histologic and clinical features in arthropod bite reactions. JAM ACAD DERMATOL 1984; 11:1043-9.
3. Hollander A. Erythema chronicum migrans: Afzelius and LipschUtz [Letter reply). J AM ACAD DERMAToL 1985; 13:664.
Leg ulcers
To the Editor: I have just read the excellent review on leg ulcers by Phillips and Dover (J AM ACAD DERMAToL 1991 ;25:961-87). Several important aspects on the pathophysiology of venous ulceration are omitted by the authors. A proper understanding of the pathophysiology is important in planning the treatment of patients with venous ulcers. The calf muscle pump of the leg is the mechanism the body has to return blood from the leg to the heart. The calf pump mechanism consists of the calf muscles, the deep
venous compartment or pump chamber, a superficial compartment connected to the deep veins via perforators, and an outflow tract (popliteal vein). During systole (i.e., calf muscle contraction), blood in the pump chamber moves cephalad through the outflow tract. During diastole (i.e., calf muscle relaxation) blood fills the emptied pump chamber with flow from the superficial veins via perforators and from the distal deep veins. Normal valvular function prevents reflux and permits one-way flow from superficial to deep and from distal to proximal. Calf pump dysfunction may occur because ofdeep venous insufficiency (primary or postthrombotic), deep venous obstruction, perforator insufficiency, superficial venous insufficiency, arteriovenous fistlilas, neuromuscular dysfunction, or a combination of the above. The result ofcalf pump dysfunction is a failure to lower venous pressure with exercise in the distal veins of the leg, a condition referred to as ambulatory venous hypertension. Ambulatory venous hypertension causes microcirculatory abnormalities, which, ifsevere enough, are believed to result in venous ulceration. As already noted, any of the components of the calf pump may contribute to calf pump dysfunction. However, the main factodn calfpump failure is usually venous insufficiency. The authors state that ''venous ulcers are usually associated with deep venous insufficiency." However, it has been shown that it is the magnitude of the reflux that is related to ulceration, regardless of whether it originates in the superficial or deep venous system. I Hanrahan et al. 2 demonstrated that 66% of the venous ulcer patients they studied with duplex imaging had multisystem disease, whereas 27% had single-system disease. Involvement of the superficial system only was found in 17%; 8% were found to have only perforator incompetence. Deep venous insufficiency, either isolated or in combination with other system disease, was found in only 49% of patients. Others have demonstrated that superficial venous insufficiency can be the sole cause of venous ulceration in a significant number of patients.3 This has important implications for therapy. Ifa venous ulcer patient has hemodynamically significant superficial venous disease, either isolated or in combination with other system disease, important hemodynamic improvement will be obtained by treating the varicose veins and the long~term prognosis greatly improved. This is generally done by sclerotherapy, surgery, or both. The same holds true for incompetent perforators, although most experienced phlebologists would advocate sclerotherapy as the treatment of choice. The treatment of deep venous insufficiency is lifelong compression. However, it is widely held among phlebologists that sclerotherapy for periulcer varicose veins and incompetent perforators will significantly improve local venous hemodynamics and speed ulcer healing. 4 Queral et al. 5 and Fronek (personal communication) found that adjunctive sclerotherapy for incompe-
Journal of the American Academy of Dermatology
488 C7orrespondence tent periulcer venous channels in deep venous insuffi.ciency significantly enhanced ulcer healing. As emphasized by the authors, it is important to exclude arterial disease in the ulcer patient. In this regard, they appropriately discuss the ankle-brachial index, although they fail to mention that this index may be falsely normal in diabetic patients because ofvessel wall stiffness. In such cases, one should be familiar with arterial waveform abnormalities. Regarding the microcirculation, the authors state that "high venous pressure is associated with capillary proliferation." Franzeck et a1.,6 using videomicroscopy, have shown that capillarydensity is reduced in extremities with advanced chronic venous insufficiency. These authors suggest that the tortuosity of the affected capillaries may result in a falsely high capillary count in histologic section and account for previous conclusions about capillary proliferation. The specifics of how the microcirculatory abnormalities produce ulceration remain to be elucidated. As mentioned by the authors two current theories are the fibrin cuff theory (oxygen diffusion barrier) and the white cell trapping theory (perfusion defect). Several recent articles have cast doubt on the hypothesis that pericapillary fibrin cuffs act as an oxygen diffusion barrier.7- IO In conclusion, although compression should serve as the cornerstone of treatment in venous ulcers, one must define the basic underlying abnormality of the venous system to form a rational individualized management plan. Steven E. Zimmet, MD Austin Regional Clinic 3708 Jefferson St. Austin, TX 78731
REFERENCES 1.
2. 3. 4. 5. 6.
7. 8.
Christopoulous D, Nicolaides AN. Noninvasive diagnosis and quantitation of popliteal reflux in the swollen and ulcerated leg. J Cardiovasc Surg 1988;29:535-9. Hanrahan LM, Araki CT, Rodriguez AA, et a1. Distribution of valvular incompetence in patients with venous stasis ulceration. J VascSurg 1991;13:805-11, Hoare MC, Nicolaides AN, Miles CR, et a1. The role of primary varicose veins in venous ulceration. Surgery 1982; 92:450-3. Stemmer R. Sclerotherapy of varicose veins. St. Gallen: Oanzoni & Cie, 1990:32. Queral LA, Criado FJ, Lilly MP, et a1. The role of sclerotherapy as an adjunct to Unna's boot for treating venous ulcers: a prospective study. J Vasc Surg 1990;11:572-5. Franzeck UK, BollingerA, Hasch R, et a1. Transcutaneous oxygen tension and capillary morphologic characteristics and density in patients with chronic venous insufficiency. Circulation 1984;70:806-11. Stibe E, Cheatle TR, Coleridge Smith PD, et a1. Liposclerotic skin: A diffusion block or perfusion problem? Phlebology 1990;5:231-6. Cheatle TR, McMullin OM, Farrah J, et a1. Skin damage in chronic venous insufficiency: Does an oxygen diffusion barrier really exist? J R Soc Med 1990;83:48-9.
9. Michel CC. Oxygen diffusion in oedematous tissue and through pericapillary fibrin cuffs. Phlebology 1990;5:22330. 10. C1audy AL, Mirshahi M, Suria C, et a1. Detection of undegraded fibrin and tumor necrosis factor-a in venous leg ulcers. JAM ACAD DERMATOL 1991;25:623-7.
Leg ulcers To the Editor: In their otherwise excellent review of the management of leg ulcers (J AM ACAD DERMATOL 1991;25:961-87),Phillips and Dover neglected to mention the importance of sodium restriction and the use of diuretics in the management of edema from stasis. Certainly, patients with mild edema will often respond to elevation and compression, in combination with dietary restriction of salt. Patients with more severe and advanced disease benefit from pharmacologic management directed toward edema control. This is especially true in patients who suffer from both arterial and venous insufficiency in whom vasodilator therapy is contemplated because these patients are predisposed to secondary volume retention. I believe that the neglect of any discussion of diuretic therapy, even brief, is an important omission in an otherwise valuable article. David L. Swanson, MD 500 Janalyn Circle Golden Valley, MN 55416
Reply To the Editor: We thank Drs. Zimmett and Swanson for their letters. Dr. Zimmett elegantly describes calf muscle pump dysfunction. The pathophysiologic mechanism of venous ulcers is complex and not yet fully understood. As we stated in our article, venous ulcers are usually associated with deep venous insufficiency, and, as Hanrahan et al. l demonstrated, multisystem incompetence is the most common finding. Although phlebologists may use sclerotherapy to treat venous ulcers, most vascular surgeons find this approach controversial. Prospective studies have shown that surgeryachieves significantly better results. 2 Dr. Zimmett's comment about the ankle-brachial index in diabetic patients underscores our discussion about this problem. As we stated in our article, the systolic blood pressure at the ankle studied with a Doppler flowmeter can sometimes be misleadingly high in the diabetic patient because of medial calcification of the arteries. In these patients, measurement of pulse amplitude with an oscillometer or plethysmograph is helpful. We agree that the role of resting and ambulatory venous function, calf muscle pump function, lymphatic
Correspondence 487
In 1985 I wrote a letter to the Editor ofthis JOURNAL about "Erythema chronicum migrans: Afzelius and Lipschiitz,"\ referring to an article by Schorr et al. 2 In turn, Dr. Alfred Hollander commented on my remarks. 3 In my letter I reported a tick bite and subsequent erythema chronicum migrans in myself, from August 1984. Checking the old calendars, I found that the tick bite and erythema must have occurred between Aug. 14 and Sept. 16, 1984. Admittedly, the remote possibility of coming into the country with both tick and (dormant) disease on Aug. 14,1984 cannot be ruled out with certainty. Given my daily routine of cycling into the Judean Hills and subsequent showering makes it unlikely that a tick bite in the groin would have escaped my attention more than one day or two. (This location had prevented me from photographically documenting the case.) As stated in my letter, \ the eruption cleared after penicillin. No histopathologic examination or Borrelia serology was done. A recent check for unrelated reasons did not reveal any antibodies to Borrelia burgdorferi. Consequently there is no confirmation of my self-diagnosis. On the other hand, the history, the tick bite (the tick being removed by myself), the characteristic clinical appearance of the erythema chronicum migrans anc,i the prompt response to penicillin favor the original diagnosis. Thus there might have been a case of Lyme disease before the "first case" as reported by Abraham et al.
Karl Holubar, MD Department of the History of Medicine Wahringer Strasse 25 A-I090 Vienna, Austria
REFERENCES 1. Holubar K. Erythema chronicum migrans: Afzelius and LipschUtz [Letter]. JAM ACAD DERMATOL 1985;13:663-4. 2. Schorr WF, Tauschek AL, Dickson KB, et al. Eosinophilic cellulitis (Wells' syndrome): histologic and clinical features in arthropod bite reactions. JAM ACAD DERMATOL 1984; 11:1043-9.
3. Hollander A. Erythema chronicum migrans: Afzelius and LipschUtz [Letter reply). J AM ACAD DERMAToL 1985; 13:664.
Leg ulcers
To the Editor: I have just read the excellent review on leg ulcers by Phillips and Dover (J AM ACAD DERMAToL 1991 ;25:961-87). Several important aspects on the pathophysiology of venous ulceration are omitted by the authors. A proper understanding of the pathophysiology is important in planning the treatment of patients with venous ulcers. The calf muscle pump of the leg is the mechanism the body has to return blood from the leg to the heart. The calf pump mechanism consists of the calf muscles, the deep
venous compartment or pump chamber, a superficial compartment connected to the deep veins via perforators, and an outflow tract (popliteal vein). During systole (i.e., calf muscle contraction), blood in the pump chamber moves cephalad through the outflow tract. During diastole (i.e., calf muscle relaxation) blood fills the emptied pump chamber with flow from the superficial veins via perforators and from the distal deep veins. Normal valvular function prevents reflux and permits one-way flow from superficial to deep and from distal to proximal. Calf pump dysfunction may occur because ofdeep venous insufficiency (primary or postthrombotic), deep venous obstruction, perforator insufficiency, superficial venous insufficiency, arteriovenous fistlilas, neuromuscular dysfunction, or a combination of the above. The result ofcalf pump dysfunction is a failure to lower venous pressure with exercise in the distal veins of the leg, a condition referred to as ambulatory venous hypertension. Ambulatory venous hypertension causes microcirculatory abnormalities, which, ifsevere enough, are believed to result in venous ulceration. As already noted, any of the components of the calf pump may contribute to calf pump dysfunction. However, the main factodn calfpump failure is usually venous insufficiency. The authors state that ''venous ulcers are usually associated with deep venous insufficiency." However, it has been shown that it is the magnitude of the reflux that is related to ulceration, regardless of whether it originates in the superficial or deep venous system. I Hanrahan et al. 2 demonstrated that 66% of the venous ulcer patients they studied with duplex imaging had multisystem disease, whereas 27% had single-system disease. Involvement of the superficial system only was found in 17%; 8% were found to have only perforator incompetence. Deep venous insufficiency, either isolated or in combination with other system disease, was found in only 49% of patients. Others have demonstrated that superficial venous insufficiency can be the sole cause of venous ulceration in a significant number of patients.3 This has important implications for therapy. Ifa venous ulcer patient has hemodynamically significant superficial venous disease, either isolated or in combination with other system disease, important hemodynamic improvement will be obtained by treating the varicose veins and the long~term prognosis greatly improved. This is generally done by sclerotherapy, surgery, or both. The same holds true for incompetent perforators, although most experienced phlebologists would advocate sclerotherapy as the treatment of choice. The treatment of deep venous insufficiency is lifelong compression. However, it is widely held among phlebologists that sclerotherapy for periulcer varicose veins and incompetent perforators will significantly improve local venous hemodynamics and speed ulcer healing. 4 Queral et al. 5 and Fronek (personal communication) found that adjunctive sclerotherapy for incompe-
Journal of the American Academy of Dermatology
488 C7orrespondence tent periulcer venous channels in deep venous insuffi.ciency significantly enhanced ulcer healing. As emphasized by the authors, it is important to exclude arterial disease in the ulcer patient. In this regard, they appropriately discuss the ankle-brachial index, although they fail to mention that this index may be falsely normal in diabetic patients because ofvessel wall stiffness. In such cases, one should be familiar with arterial waveform abnormalities. Regarding the microcirculation, the authors state that "high venous pressure is associated with capillary proliferation." Franzeck et a1.,6 using videomicroscopy, have shown that capillarydensity is reduced in extremities with advanced chronic venous insufficiency. These authors suggest that the tortuosity of the affected capillaries may result in a falsely high capillary count in histologic section and account for previous conclusions about capillary proliferation. The specifics of how the microcirculatory abnormalities produce ulceration remain to be elucidated. As mentioned by the authors two current theories are the fibrin cuff theory (oxygen diffusion barrier) and the white cell trapping theory (perfusion defect). Several recent articles have cast doubt on the hypothesis that pericapillary fibrin cuffs act as an oxygen diffusion barrier.7- IO In conclusion, although compression should serve as the cornerstone of treatment in venous ulcers, one must define the basic underlying abnormality of the venous system to form a rational individualized management plan. Steven E. Zimmet, MD Austin Regional Clinic 3708 Jefferson St. Austin, TX 78731
REFERENCES 1.
2. 3. 4. 5. 6.
7. 8.
Christopoulous D, Nicolaides AN. Noninvasive diagnosis and quantitation of popliteal reflux in the swollen and ulcerated leg. J Cardiovasc Surg 1988;29:535-9. Hanrahan LM, Araki CT, Rodriguez AA, et a1. Distribution of valvular incompetence in patients with venous stasis ulceration. J VascSurg 1991;13:805-11, Hoare MC, Nicolaides AN, Miles CR, et a1. The role of primary varicose veins in venous ulceration. Surgery 1982; 92:450-3. Stemmer R. Sclerotherapy of varicose veins. St. Gallen: Oanzoni & Cie, 1990:32. Queral LA, Criado FJ, Lilly MP, et a1. The role of sclerotherapy as an adjunct to Unna's boot for treating venous ulcers: a prospective study. J Vasc Surg 1990;11:572-5. Franzeck UK, BollingerA, Hasch R, et a1. Transcutaneous oxygen tension and capillary morphologic characteristics and density in patients with chronic venous insufficiency. Circulation 1984;70:806-11. Stibe E, Cheatle TR, Coleridge Smith PD, et a1. Liposclerotic skin: A diffusion block or perfusion problem? Phlebology 1990;5:231-6. Cheatle TR, McMullin OM, Farrah J, et a1. Skin damage in chronic venous insufficiency: Does an oxygen diffusion barrier really exist? J R Soc Med 1990;83:48-9.
9. Michel CC. Oxygen diffusion in oedematous tissue and through pericapillary fibrin cuffs. Phlebology 1990;5:22330. 10. C1audy AL, Mirshahi M, Suria C, et a1. Detection of undegraded fibrin and tumor necrosis factor-a in venous leg ulcers. JAM ACAD DERMATOL 1991;25:623-7.
Leg ulcers To the Editor: In their otherwise excellent review of the management of leg ulcers (J AM ACAD DERMATOL 1991;25:961-87),Phillips and Dover neglected to mention the importance of sodium restriction and the use of diuretics in the management of edema from stasis. Certainly, patients with mild edema will often respond to elevation and compression, in combination with dietary restriction of salt. Patients with more severe and advanced disease benefit from pharmacologic management directed toward edema control. This is especially true in patients who suffer from both arterial and venous insufficiency in whom vasodilator therapy is contemplated because these patients are predisposed to secondary volume retention. I believe that the neglect of any discussion of diuretic therapy, even brief, is an important omission in an otherwise valuable article. David L. Swanson, MD 500 Janalyn Circle Golden Valley, MN 55416
Reply To the Editor: We thank Drs. Zimmett and Swanson for their letters. Dr. Zimmett elegantly describes calf muscle pump dysfunction. The pathophysiologic mechanism of venous ulcers is complex and not yet fully understood. As we stated in our article, venous ulcers are usually associated with deep venous insufficiency, and, as Hanrahan et al. l demonstrated, multisystem incompetence is the most common finding. Although phlebologists may use sclerotherapy to treat venous ulcers, most vascular surgeons find this approach controversial. Prospective studies have shown that surgeryachieves significantly better results. 2 Dr. Zimmett's comment about the ankle-brachial index in diabetic patients underscores our discussion about this problem. As we stated in our article, the systolic blood pressure at the ankle studied with a Doppler flowmeter can sometimes be misleadingly high in the diabetic patient because of medial calcification of the arteries. In these patients, measurement of pulse amplitude with an oscillometer or plethysmograph is helpful. We agree that the role of resting and ambulatory venous function, calf muscle pump function, lymphatic
