- Email: [email protected]
Kaposi's sarcoma: An unusual cause of persistent bilateral leg edema in old age
European Geriatric Medicine 3 (2012) 114–116
Available online at
www.sciencedirect.com
EGM clinical case
Kaposi’s sarcoma: An unusual cause of persistent bilateral leg edema in old age S. Aras a,*, M. Varli a, A. Yalcin a, O. Karaaslan a, A.B. Caglar b, T. Atli a a b
Department of Geriatric Medicine, Ankara University School of Medicine, Cebeci, Ankara 06110, Turkey Department of Dermatology, Ankara University School of Medicine, Sıhhiye, Ankara 06110, Turkey
A R T I C L E I N F O
2. Case presentation
Article history: Received 4 January 2012 Accepted 16 January 2012 Available online 29 February 2012
A 65 years old man admitted to our geriatric department with complaint of bilateral lower extremity swelling of 3 months duration. The leg edema worsened in the last month despite treatments with the sodium restriction, diuretics and venous insufficiency medications. Our patient had been examined by the other specialists in several hospitals, but cause of the leg edema had not been clarified. The patient was hospitalized for further evaluation and treatment because of persistent edema. He had hypertension, chronic obstructive pulmonary disease, obesity and type 2 diabetes mellitus. He was a non-smoker and he had no known history of trauma, deep venous thrombosis or recent surgeries. He had no symptoms of angina, orthopnea or paroxysmal nocturnal dyspnea. He was a former truck driver traveling abroad. His family history was unremarkable except that his father had diabetes mellitus. The patient’s medications included acetylsalicylic acid, telmisartan/hydrochlorothiazide, metformin, glimepride, acarbose, spironolactone, inhaler formoterol plus budenoside at the time of hospitalization. A physical examination revealed prolonged expirium, hepatomegaly (1–2 cm) and firm, mild red, non-pitting and painless edema of both feet and lower legs, reaching knees. His right leg edema was more prominent than his left leg edema. He had no evidence of chronic venous stasis changes in both lower extremities, and no collateral veins were present. Findings on examination of the heart were unremarkable. He had mild anemia (hemoglobin; 11.2 g/dL). A total protein and albumin levels were 6.2 and 3.1 g/dL, respectively. Hepatitis B surface antigen was found positive. In addition, serologic testing for HIV was negative. The other laboratory test results, including leukocyte and thrombosit counts, blood sugar, liver and renal function tests, electrolytes, urinalysis, prostate specific antigen and thyroid function tests were within normal limits. Chest radiograph was notable for slight increased bronchovascular branching in each basal zone. There was no pulmonary congestion or pleural effusion. Left ventricular hypertrophy signs were found in electrocardiogram. Cardiac functions were further evaluated by echocardiography. The echocardiographic evaluation revealed left ventricular concentric hypertrophy and normal left ventricular ejection fraction (62%). Furthermore, there were no signs of ischemic changes, pulmonary hypertension, diastolic dysfunction or right ventricular failure. Bilateral lower extremity venous doppler ultrasonography revealed no evidence of DVT and venous insufficiency. The only finding was subcutaneous edema.
Keywords: Kaposi’s sarkoma Leg edema Elderly
1. Introduction Bilateral leg edema is common among the elderly patients and a major concern in geriatric medicine. Symmetric leg edema is generally due to chronic venous insufficiency. Other systemic diseases such as congestive heart failure, renal or liver disease are the next common causes. In addition, unilateral edema is usually associated with an underlying condition such as lymphatic obstruction secondary to tumor (e.g., prostate cancer, ovarian cancer, lymphoma) or radiation treatment and deep vein thrombosis (DVT) [1]. The classical form of Kaposi’s sarcoma (KS) is a rare vascular tumor affecting elderly men of Mediterranean and Eastern European. Patients with KS usually present with skin lesions or lymph nodes involvement of the lower extremities. Visceral involvement, particularly in the lung and gastrointestinal tract occurs less frequently. In addition, human immunodeficiency virus (HIV) associated with KS is the most common tumor affecting the patients with acquired immunodeficiency syndrome (AIDS). In contrast to other presentations of the disease, it is usually a systemic disorder [2]. We report a rare case of KS in a 65-year-old male patient with bilateral leg edema, which is refractory to conventional therapy and without evidence of HIV.
* Corresponding author. 446, Sokak Dog˘ukent Caddesi, Vadi ikizleri sitesi 3B/7, Birlik, Ankara, Turkey. Tel.: +90 31 25 95 68 97; fax: +90 31 23 62 34 41. E-mail address: [email protected] (S. Aras).
1878-7649/$ – see front matter ß 2012 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved. doi:10.1016/j.eurger.2012.01.008
S. Aras et al. / European Geriatric Medicine 3 (2012) 114–116
Fig. 1. Kaposi’s sarcoma on the lower extremities with edema.
On admission to our hospital, skin examination was normal, except for edema. After a short period of hospitalization, multiple, purple-colored, palpable plaques and nodules appeared on anterior parts of both legs and feet (Fig. 1). A skin biopsy was performed for initial diagnosis of cutaneous lesions. Spindle cell mesenchymal tumor was observed in biopsy specimens. After immunohistochemical stain, CD31 (+) was found strongly positive. There is also nuclear staining with Human herpes virus type 8 (HHV8). Histological and immunohistological findings were consistent with a diagnosis of HIV negative KS. Other diagnostic evaluations, including upper gastrointestinal endoscopy, colonoscopy and positron emission tomography (PET) scan were performed to determine the possible spread of the disease to other sites. Endoscopy and colonoscopy was normal, but PET scan showed increased activity at subcutaneous tissue and subcutaneous fat tissue on distal parts of both lower extremities. In our patient, since the skin lesions were multiple, widespread and varied in size, there was no chance for surgical cure. Therefore, three million units per day interferon alpha-2b therapy three times a week was given. The lower extremity edema gradually improved during the first weeks of treatment with interferon. The patient was also referred to radiation oncology clinic for local radiotherapy in conjunction with interferon therapy. 3. Discussion Lower limb edema is a common problem in older patients, with a wide range of possible causes. The differential diagnosis includes systemic illnesses such as heart failure, liver and renal diseases, malnutrition, and thyroid disorder, or local conditions such as pelvic tumors, infections, trauma, and venous thrombosis. Medications, particularly calcium-channel-blockers, nonsteroidal anti-inflammatory drugs, corticosteroids can induce leg edema [3]. This case reports on a rare case of KS in the older patient with bilateral leg edema. KS was uncommon, but it can lead to serious complications. There are four types according to the histological classification: classical, epidemic (AIDS-related), endemic and posttransplant [4]. Nodular or severe skin lesions without visceral involvement or severe disease with visceral involvement are two different clinical courses of KS. Classical KS is generally known as a slowly progressive tumor involving the skin surfaces of lower extremities [5].
115
In the present case, the patient complained of symmetric leg edema without symptoms of venous insufficiency, heart failure, renal and liver disease. In most cases, edema etiology was easily found by history, physical examination and basic laboratory tests but in some cases, it is difficult to determine the etiology of edema [1]. In this case, the definitive diagnosis of edema could not been made with conventional laboratory tests because skin lesions of KS were interestingly appeared approximately 3 months later from development of leg edema. In some cases, the edema may be observed in the absence of cutaneous lesions and may obscure the diagnosis. Furthermore, skin lesions may occur late in the course of KS. [6] In our case, there was only skin involvement but no visceral involvement and he had symmetric, firm, non-pitting lymphedema. Pitting or non-pitting feature of edema may be important in differential diagnosis [1]. The blockage of lymphatic drainage due to the lymphatic involvement or the external compression of lymphatics by cutaneous lesions is probably responsible for refractory edema in the lower limbs. As in our case, the presence of KS lesions may be the only distinguishing feature. KS lesions may emerge small, innocuouslooking skin blemishes that are easily overlooked or KS may be mistaken in the skin for ecchymoses, cellulitis, vasculitis, or arteriovenous malformations [2]. Therefore, a careful skin and physical examination should be performed in elderly patients with edema, in particular lympedema. Although KS is the most common tumor-affecting patients with AIDS, sporadic cases in HIV-negative patients have been reported [7]. Initiation of KS is associated with HIV infection and its mitogenic effects. Recent studies also show that HHV8 is obtained from blood and tissue samples of KS patients with a rate of 95% [8]. HHV8-infected cells play a key role in the pathogenesis of KS [9]. In the present case, HHV8 was detected on the skin biopsy specimens. There is no curative treatment of KS. Surgery or radiotherapy is suitable for localized skin or visceral lesions. Doxorubicin can be a choice as a single agent or with other anti-neoplastic or anti-viral agents for systemic disease [10]. Low dose interferon-a was found effective in some studies [11]. In our case, lesions were limited to the skin but surgery could not be performed because of widespread of skin lesions. Therefore, Interferon plus local radiotherapy was planned. 4. Conclusion This case included bilateral leg edema accompanied by the skin lesions manifested as an unusual condition of KS in old age. In daily practice, skin lesions are along with a number of clinical conditions and can be an important sign of systemic diseases. Thus, not only dermatologist but also other clinicians should be familiar with the skin lesions related to a variety of diseases. In some patients, skin lesions can be late finding of the systemic diseases and these lesions can also be overlooked or confused. A careful history and a physical examination with particular awareness are of special importance. If the clinically suspicious lesions are detected, biopsy and histological examination to identify these lesions should be considered. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Thaler HW, Wirnsberger G, Pienaar S, Roller RE. Bilateral leg edema in the elderly. Clinical considerations and treatment options. Eur Geriatr Med 2010;1:353–7. [2] Aboulafia DM. Kaposi’s sarcoma. Clin Dermatol 2001;19:269–83.
116
S. Aras et al. / European Geriatric Medicine 3 (2012) 114–116
[3] Ciocon JO, Fernandez BB, Ciocon DG. Leg edema: clinical clues to the differential diagnosis. Geriatrics 1993;48:34–40. [4] Fister M, Vogt B. Painless red-violet skin lesions during immunosupression. Ann Diagn Pathol 1997;1:57–64. [5] Schwartz RA. Kaposi’s sarcoma: an update. J Surg Oncol 2004;87:146–51. [6] Allen PJ, Gillespie DL, Redfield RR, Gomez ER. Lower extremity lymphedema caused by acquired immune deficiency syndrome-related Kaposi’s sarcoma: case report and review of the literature. J Vasc Surg 1995;22:178–81. [7] Kosmidis C, Efthimiadis C, Anthimidis G, Karayannopoulou G, Grigoriou M, Vassiliadou K, et al. Kaposi’s sarcoma of the hand mimicking squamous cell carcinoma in a woman with no evidence of HIV infection: a case report. J Med Case Reports 2008;2:213.
[8] Gao SJ, Kingsley L, Hoover DR, SpiraTJ, Rinaldo CR, Saah A, et al. Seroconversion to antibodies against Kaposi’s sarcoma associated herpes virus related latent nuclear antigens before the development of Kaposi’s sarcoma. N Engl J Med 1996;335:233–41. [9] Brambilla L, Tourlaki A, Ferrucci S, Brambati M, Boneschi V. Treatment of classic Kaposi’s sarcoma-associated lymphedema with elastic stockings. J Dermatol 2006;33:451–6. [10] Newell M, Milliken S, Goldstein D, Lewis C, Boyle M, Dolan G, et al. A phase II study of liposomal doxorubicin in the treatment of HIV-related Kaposi’s sarcoma. J Gen Virol 1999;80:549–55. [11] Tur E, Brenner S. Classic Kaposi’s sarcoma: low-dose interferon alfa treatment. Br J Haematol 1998;103:788–90.
Available online at
www.sciencedirect.com
EGM clinical case
Kaposi’s sarcoma: An unusual cause of persistent bilateral leg edema in old age S. Aras a,*, M. Varli a, A. Yalcin a, O. Karaaslan a, A.B. Caglar b, T. Atli a a b
Department of Geriatric Medicine, Ankara University School of Medicine, Cebeci, Ankara 06110, Turkey Department of Dermatology, Ankara University School of Medicine, Sıhhiye, Ankara 06110, Turkey
A R T I C L E I N F O
2. Case presentation
Article history: Received 4 January 2012 Accepted 16 January 2012 Available online 29 February 2012
A 65 years old man admitted to our geriatric department with complaint of bilateral lower extremity swelling of 3 months duration. The leg edema worsened in the last month despite treatments with the sodium restriction, diuretics and venous insufficiency medications. Our patient had been examined by the other specialists in several hospitals, but cause of the leg edema had not been clarified. The patient was hospitalized for further evaluation and treatment because of persistent edema. He had hypertension, chronic obstructive pulmonary disease, obesity and type 2 diabetes mellitus. He was a non-smoker and he had no known history of trauma, deep venous thrombosis or recent surgeries. He had no symptoms of angina, orthopnea or paroxysmal nocturnal dyspnea. He was a former truck driver traveling abroad. His family history was unremarkable except that his father had diabetes mellitus. The patient’s medications included acetylsalicylic acid, telmisartan/hydrochlorothiazide, metformin, glimepride, acarbose, spironolactone, inhaler formoterol plus budenoside at the time of hospitalization. A physical examination revealed prolonged expirium, hepatomegaly (1–2 cm) and firm, mild red, non-pitting and painless edema of both feet and lower legs, reaching knees. His right leg edema was more prominent than his left leg edema. He had no evidence of chronic venous stasis changes in both lower extremities, and no collateral veins were present. Findings on examination of the heart were unremarkable. He had mild anemia (hemoglobin; 11.2 g/dL). A total protein and albumin levels were 6.2 and 3.1 g/dL, respectively. Hepatitis B surface antigen was found positive. In addition, serologic testing for HIV was negative. The other laboratory test results, including leukocyte and thrombosit counts, blood sugar, liver and renal function tests, electrolytes, urinalysis, prostate specific antigen and thyroid function tests were within normal limits. Chest radiograph was notable for slight increased bronchovascular branching in each basal zone. There was no pulmonary congestion or pleural effusion. Left ventricular hypertrophy signs were found in electrocardiogram. Cardiac functions were further evaluated by echocardiography. The echocardiographic evaluation revealed left ventricular concentric hypertrophy and normal left ventricular ejection fraction (62%). Furthermore, there were no signs of ischemic changes, pulmonary hypertension, diastolic dysfunction or right ventricular failure. Bilateral lower extremity venous doppler ultrasonography revealed no evidence of DVT and venous insufficiency. The only finding was subcutaneous edema.
Keywords: Kaposi’s sarkoma Leg edema Elderly
1. Introduction Bilateral leg edema is common among the elderly patients and a major concern in geriatric medicine. Symmetric leg edema is generally due to chronic venous insufficiency. Other systemic diseases such as congestive heart failure, renal or liver disease are the next common causes. In addition, unilateral edema is usually associated with an underlying condition such as lymphatic obstruction secondary to tumor (e.g., prostate cancer, ovarian cancer, lymphoma) or radiation treatment and deep vein thrombosis (DVT) [1]. The classical form of Kaposi’s sarcoma (KS) is a rare vascular tumor affecting elderly men of Mediterranean and Eastern European. Patients with KS usually present with skin lesions or lymph nodes involvement of the lower extremities. Visceral involvement, particularly in the lung and gastrointestinal tract occurs less frequently. In addition, human immunodeficiency virus (HIV) associated with KS is the most common tumor affecting the patients with acquired immunodeficiency syndrome (AIDS). In contrast to other presentations of the disease, it is usually a systemic disorder [2]. We report a rare case of KS in a 65-year-old male patient with bilateral leg edema, which is refractory to conventional therapy and without evidence of HIV.
* Corresponding author. 446, Sokak Dog˘ukent Caddesi, Vadi ikizleri sitesi 3B/7, Birlik, Ankara, Turkey. Tel.: +90 31 25 95 68 97; fax: +90 31 23 62 34 41. E-mail address: [email protected] (S. Aras).
1878-7649/$ – see front matter ß 2012 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved. doi:10.1016/j.eurger.2012.01.008
S. Aras et al. / European Geriatric Medicine 3 (2012) 114–116
Fig. 1. Kaposi’s sarcoma on the lower extremities with edema.
On admission to our hospital, skin examination was normal, except for edema. After a short period of hospitalization, multiple, purple-colored, palpable plaques and nodules appeared on anterior parts of both legs and feet (Fig. 1). A skin biopsy was performed for initial diagnosis of cutaneous lesions. Spindle cell mesenchymal tumor was observed in biopsy specimens. After immunohistochemical stain, CD31 (+) was found strongly positive. There is also nuclear staining with Human herpes virus type 8 (HHV8). Histological and immunohistological findings were consistent with a diagnosis of HIV negative KS. Other diagnostic evaluations, including upper gastrointestinal endoscopy, colonoscopy and positron emission tomography (PET) scan were performed to determine the possible spread of the disease to other sites. Endoscopy and colonoscopy was normal, but PET scan showed increased activity at subcutaneous tissue and subcutaneous fat tissue on distal parts of both lower extremities. In our patient, since the skin lesions were multiple, widespread and varied in size, there was no chance for surgical cure. Therefore, three million units per day interferon alpha-2b therapy three times a week was given. The lower extremity edema gradually improved during the first weeks of treatment with interferon. The patient was also referred to radiation oncology clinic for local radiotherapy in conjunction with interferon therapy. 3. Discussion Lower limb edema is a common problem in older patients, with a wide range of possible causes. The differential diagnosis includes systemic illnesses such as heart failure, liver and renal diseases, malnutrition, and thyroid disorder, or local conditions such as pelvic tumors, infections, trauma, and venous thrombosis. Medications, particularly calcium-channel-blockers, nonsteroidal anti-inflammatory drugs, corticosteroids can induce leg edema [3]. This case reports on a rare case of KS in the older patient with bilateral leg edema. KS was uncommon, but it can lead to serious complications. There are four types according to the histological classification: classical, epidemic (AIDS-related), endemic and posttransplant [4]. Nodular or severe skin lesions without visceral involvement or severe disease with visceral involvement are two different clinical courses of KS. Classical KS is generally known as a slowly progressive tumor involving the skin surfaces of lower extremities [5].
115
In the present case, the patient complained of symmetric leg edema without symptoms of venous insufficiency, heart failure, renal and liver disease. In most cases, edema etiology was easily found by history, physical examination and basic laboratory tests but in some cases, it is difficult to determine the etiology of edema [1]. In this case, the definitive diagnosis of edema could not been made with conventional laboratory tests because skin lesions of KS were interestingly appeared approximately 3 months later from development of leg edema. In some cases, the edema may be observed in the absence of cutaneous lesions and may obscure the diagnosis. Furthermore, skin lesions may occur late in the course of KS. [6] In our case, there was only skin involvement but no visceral involvement and he had symmetric, firm, non-pitting lymphedema. Pitting or non-pitting feature of edema may be important in differential diagnosis [1]. The blockage of lymphatic drainage due to the lymphatic involvement or the external compression of lymphatics by cutaneous lesions is probably responsible for refractory edema in the lower limbs. As in our case, the presence of KS lesions may be the only distinguishing feature. KS lesions may emerge small, innocuouslooking skin blemishes that are easily overlooked or KS may be mistaken in the skin for ecchymoses, cellulitis, vasculitis, or arteriovenous malformations [2]. Therefore, a careful skin and physical examination should be performed in elderly patients with edema, in particular lympedema. Although KS is the most common tumor-affecting patients with AIDS, sporadic cases in HIV-negative patients have been reported [7]. Initiation of KS is associated with HIV infection and its mitogenic effects. Recent studies also show that HHV8 is obtained from blood and tissue samples of KS patients with a rate of 95% [8]. HHV8-infected cells play a key role in the pathogenesis of KS [9]. In the present case, HHV8 was detected on the skin biopsy specimens. There is no curative treatment of KS. Surgery or radiotherapy is suitable for localized skin or visceral lesions. Doxorubicin can be a choice as a single agent or with other anti-neoplastic or anti-viral agents for systemic disease [10]. Low dose interferon-a was found effective in some studies [11]. In our case, lesions were limited to the skin but surgery could not be performed because of widespread of skin lesions. Therefore, Interferon plus local radiotherapy was planned. 4. Conclusion This case included bilateral leg edema accompanied by the skin lesions manifested as an unusual condition of KS in old age. In daily practice, skin lesions are along with a number of clinical conditions and can be an important sign of systemic diseases. Thus, not only dermatologist but also other clinicians should be familiar with the skin lesions related to a variety of diseases. In some patients, skin lesions can be late finding of the systemic diseases and these lesions can also be overlooked or confused. A careful history and a physical examination with particular awareness are of special importance. If the clinically suspicious lesions are detected, biopsy and histological examination to identify these lesions should be considered. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Thaler HW, Wirnsberger G, Pienaar S, Roller RE. Bilateral leg edema in the elderly. Clinical considerations and treatment options. Eur Geriatr Med 2010;1:353–7. [2] Aboulafia DM. Kaposi’s sarcoma. Clin Dermatol 2001;19:269–83.
116
S. Aras et al. / European Geriatric Medicine 3 (2012) 114–116
[3] Ciocon JO, Fernandez BB, Ciocon DG. Leg edema: clinical clues to the differential diagnosis. Geriatrics 1993;48:34–40. [4] Fister M, Vogt B. Painless red-violet skin lesions during immunosupression. Ann Diagn Pathol 1997;1:57–64. [5] Schwartz RA. Kaposi’s sarcoma: an update. J Surg Oncol 2004;87:146–51. [6] Allen PJ, Gillespie DL, Redfield RR, Gomez ER. Lower extremity lymphedema caused by acquired immune deficiency syndrome-related Kaposi’s sarcoma: case report and review of the literature. J Vasc Surg 1995;22:178–81. [7] Kosmidis C, Efthimiadis C, Anthimidis G, Karayannopoulou G, Grigoriou M, Vassiliadou K, et al. Kaposi’s sarcoma of the hand mimicking squamous cell carcinoma in a woman with no evidence of HIV infection: a case report. J Med Case Reports 2008;2:213.
[8] Gao SJ, Kingsley L, Hoover DR, SpiraTJ, Rinaldo CR, Saah A, et al. Seroconversion to antibodies against Kaposi’s sarcoma associated herpes virus related latent nuclear antigens before the development of Kaposi’s sarcoma. N Engl J Med 1996;335:233–41. [9] Brambilla L, Tourlaki A, Ferrucci S, Brambati M, Boneschi V. Treatment of classic Kaposi’s sarcoma-associated lymphedema with elastic stockings. J Dermatol 2006;33:451–6. [10] Newell M, Milliken S, Goldstein D, Lewis C, Boyle M, Dolan G, et al. A phase II study of liposomal doxorubicin in the treatment of HIV-related Kaposi’s sarcoma. J Gen Virol 1999;80:549–55. [11] Tur E, Brenner S. Classic Kaposi’s sarcoma: low-dose interferon alfa treatment. Br J Haematol 1998;103:788–90.