Ophthalmologic Manifestations of Kaposi Sarcoma: Background, Pathophysiology, Epidemiology
In 1872, Kaposi was the first to report an idiopathic, multiple-pigmented sarcoma of the skin that predominantly affected elderly men of Mediterranean or Ashkenazi ancestry.
Transplant-related Kaposi sarcoma has been reported in patients with renal transplants on immunosuppressive therapy.
Epidemic Kaposi sarcoma, better known as AIDS-related Kaposi sarcoma, commonly affects homosexual males with AIDS.
Whether the 4 variants of Kaposi sarcoma represent the same disease process or different processes that manifest the same end-stage lesion is unclear.
Although the etiology has not been elucidated, the human herpesvirus 8 (HHV-8) or Kaposi sarcoma–associated herpesvirus (KSHV) has been implicated.Chang et al identified this virus in more than 90% of patients with AIDS-related Kaposi sarcoma.KSHV is also the etiological agent of 3 other AIDS-related lymphoproliferative disorders: (1) primary effusion lymphoma, (2) the plasma-cell variant of multicentric Castleman disease, and (3) the vascular tumor recurrent angiolymphoid hyperplasia with eosinophilia.
The life cycle of KSHV consists of a latent and a lytic replication phase. During latent infection, only a limited number of KSHV genes are expressed. The switch between the latent form and lytic replication is regulated by epigenetic factors. Reactive oxygen species hydrogen peroxide also mediates KSHV reactivation from latency.However, induction of lytic replication by environmental stimuli or chemical agents is important for the spread of KSHV, the persistence of infection, the evasion of host immune response, and induction of KSHV-related malignancies (by modification of the host genome).
Kaposi sarcoma is most likely caused by multiple factors, including deregulated expression of oncogenes and oncosuppressor genes by KSHV/HHV-8 combined with decreased immune surveillance and the release of cytokines (viral interleukin [vIL]–6) and growth factors, by HIV acting on infected cells.
vIL-6 is a product of KSHV expressed in latently infected cells and to a higher degree during viral replication. Secretion of vIL-6 is generally poor, but vIL-6 has the potential to induce a wide range of biological effects, such as inducing vascular endothelial growth factor.
KSHV/HHV-8 mediates oncogenesis, although the exact mechanisms by which this happens has not yet been fully elucidated; numerous KSHV/HHV-8 viral oncogenes may contribute to neoplasia formation.
United States
Prior to 1981, fewer than 25 reported cases of ophthalmic Kaposi sarcoma existed in the literature. Currently, the overwhelming majority of ophthalmic Kaposi sarcoma is AIDS related. In 1986, the Centers for Disease Control and Prevention (CDC) reported that Kaposi sarcoma occurs in approximately 24% of patients with AIDS and in 35% of all homosexual men with AIDS.The CDC reported that during the period from 1992-1997, Kaposi sarcoma occurred in 23.8% of males with AIDS and in 27.4% of all homosexual men with AIDS. During the same period, only 2.3% of women with AIDS developed Kaposi sarcoma.
Ophthalmic involvement occurs in 20-24% of patients with AIDS-related Kaposi sarcoma. Ophthalmic presentation was the initial manifestation of AIDS-related Kaposi sarcoma in 4-12% of patients. Eye lesions are neither an early nor a late manifestation of Kaposi sarcoma. A review of the literature reports that most eye lesions involve the conjunctivae or eyelids; 10-75% of patients have conjunctival lesions, and 25-80% of patients have eyelid lesions.
In recent years, the incidence of Kaposi sarcoma among HIV patients has significantly declined, from 60.6% in 1992 to 19.7% in 1997. The exact cause for this decline is unclear, but the introduction of protease inhibitors, combination HIV therapy, and safer sexual practices may have played significant roles.
Kaposi sarcoma is linked to significant morbidity and mortality; it can disseminate to visceral organs (ie, lungs, liver, adrenal glands, kidneys, bone marrow, GI tract) and possibly cause bowel obstruction, lower extremity edema, shortness of breath, hemorrhage, and pain. Visceral and lung involvement usually portends a poor prognosis.
Generally, ophthalmic Kaposi sarcoma is indolent. Ocular tumor growth can result in severe damage to the ocular adnexa, the ocular surface, and even the orbit and choroid.
Involvement of the eyelids can cause significant disfigurement and lid dysfunction. Trichiasis can develop from mechanical ectropion or entropion. Lagophthalmos and trichiasis can result in profound irritation and dryness, infections, and corneal scarring. Large lid tumors can induce irregular corneal astigmatism. Conjunctival involvement may result in recurrent subconjunctival hemorrhages and may even be associated with squamous cell carcinoma in patients with HIV infection. Ultimately, vision could be lost from lid dysfunction, corneal surface changes, or visual obstruction.
Classic Kaposi sarcoma usually involves elderly men with Mediterranean or Ashkenazi ancestry. Endemic Kaposi sarcoma usually involves young black males from central Africa.Transplant-related or AIDS-related Kaposi sarcoma has no racial predilection.
Classic Kaposi sarcoma usually involves elderly men. Endemic Kaposi sarcoma usually involves young males. AIDS-related Kaposi sarcoma predominantly involves homosexual males.
Classic Kaposi sarcoma affects the older population. Endemic Kaposi sarcoma affects children with a male-to-female ratio of 1:1; after puberty, males are predominantly affected. AIDS-related Kaposi sarcoma usually affects males aged 20-49 years.
Clinical Presentation
Jacqueline Freudenthal, MD Co-Investigator, Ophthalmic Consultants Centre, Toronto
Jacqueline Freudenthal, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, Canadian Ophthalmological Society
Coauthor(s)
Kevin Ryan Yuhan, MD Attending Physician, Cornea, Cataract, Refractive and External Diseases, Southern California Permanente Medical Group
Kevin Ryan Yuhan, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Association for Research in Vision and Ophthalmology, Phi Beta Kappa, American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery
Timothy T You, MD Consulting Surgeon in Ophthalmology, Private Practice
Timothy T You, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists
Specialty Editor Board
Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Glaucoma Society
Christopher J Rapuano, MD Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital
Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Ophthalmological Society, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, International Society of Refractive Surgery, Cornea Society, Eye Bank Association of America
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, Allergan, Bausch & Lomb, Bio-Tissue, Shire, TearScience, TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Allergan, Bausch & Lomb, Bio-Tissue, TearScience.
Chief Editor
Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology
Acknowledgements
Anastasios J Kanellopoulos, MD Assistant Program Director, Clinical Associate Professor, Department of Ophthalmology, Manhattan Eye, Ear, and Throat Hospital, New York University
Anastasios J Kanellopoulos, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, Eye Bank Association of America, and International Society of Refractive Surgery
References
Section of eyelid with Kaposi sarcoma lesion under high magnification. This tissue section demonstrates increased angiogenesis and spindle-shaped cells. Courtesy of Ben Glasgow, MD, University of California, Los Angeles, Department of Ophthalmology, Jules Stein Eye Institute.
Section of eyelid with Kaposi sarcoma lesion under high magnification. This tissue section demonstrates endothelium-lined vascular channels and proliferation of spindle-shaped cells. Increased angiogenesis with erythrocyte extravasation is observed. Courtesy of Ben Glasgow, MD, University of California, Los Angeles, Department of Ophthalmology, Jules Stein Eye Institute.
The inferior conjunctiva is involved more commonly than the superior conjunctiva in Kaposi sarcoma. Courtesy of Gary N Holland, MD, University of California, Los Angeles, Department of Ophthalmology, Jules Stein Eye Institute.
Kaposi sarcoma involvement of the eyelid. Courtesy of Gary N Holland, MD, University of California, Los Angeles, Department of Ophthalmology, Jules Stein Eye Institute.
Background
In 1872, Kaposi was the first to report an idiopathic, multiple-pigmented sarcoma of the skin that predominantly affected elderly men of Mediterranean or Ashkenazi ancestry.
Transplant-related Kaposi sarcoma has been reported in patients with renal transplants on immunosuppressive therapy.
Epidemic Kaposi sarcoma, better known as AIDS-related Kaposi sarcoma, commonly affects homosexual males with AIDS.
Pathophysiology
Whether the 4 variants of Kaposi sarcoma represent the same disease process or different processes that manifest the same end-stage lesion is unclear.
Although the etiology has not been elucidated, the human herpesvirus 8 (HHV-8) or Kaposi sarcoma–associated herpesvirus (KSHV) has been implicated.Chang et al identified this virus in more than 90% of patients with AIDS-related Kaposi sarcoma.KSHV is also the etiological agent of 3 other AIDS-related lymphoproliferative disorders: (1) primary effusion lymphoma, (2) the plasma-cell variant of multicentric Castleman disease, and (3) the vascular tumor recurrent angiolymphoid hyperplasia with eosinophilia.
The life cycle of KSHV consists of a latent and a lytic replication phase. During latent infection, only a limited number of KSHV genes are expressed. The switch between the latent form and lytic replication is regulated by epigenetic factors. Reactive oxygen species hydrogen peroxide also mediates KSHV reactivation from latency.However, induction of lytic replication by environmental stimuli or chemical agents is important for the spread of KSHV, the persistence of infection, the evasion of host immune response, and induction of KSHV-related malignancies (by modification of the host genome).
Kaposi sarcoma is most likely caused by multiple factors, including deregulated expression of oncogenes and oncosuppressor genes by KSHV/HHV-8 combined with decreased immune surveillance and the release of cytokines (viral interleukin [vIL]–6) and growth factors, by HIV acting on infected cells.
vIL-6 is a product of KSHV expressed in latently infected cells and to a higher degree during viral replication. Secretion of vIL-6 is generally poor, but vIL-6 has the potential to induce a wide range of biological effects, such as inducing vascular endothelial growth factor.
KSHV/HHV-8 mediates oncogenesis, although the exact mechanisms by which this happens has not yet been fully elucidated; numerous KSHV/HHV-8 viral oncogenes may contribute to neoplasia formation.
Epidemiology
Frequency
United States
Prior to 1981, fewer than 25 reported cases of ophthalmic Kaposi sarcoma existed in the literature. Currently, the overwhelming majority of ophthalmic Kaposi sarcoma is AIDS related. In 1986, the Centers for Disease Control and Prevention (CDC) reported that Kaposi sarcoma occurs in approximately 24% of patients with AIDS and in 35% of all homosexual men with AIDS.The CDC reported that during the period from 1992-1997, Kaposi sarcoma occurred in 23.8% of males with AIDS and in 27.4% of all homosexual men with AIDS. During the same period, only 2.3% of women with AIDS developed Kaposi sarcoma.
Ophthalmic involvement occurs in 20-24% of patients with AIDS-related Kaposi sarcoma. Ophthalmic presentation was the initial manifestation of AIDS-related Kaposi sarcoma in 4-12% of patients. Eye lesions are neither an early nor a late manifestation of Kaposi sarcoma. A review of the literature reports that most eye lesions involve the conjunctivae or eyelids; 10-75% of patients have conjunctival lesions, and 25-80% of patients have eyelid lesions.
In recent years, the incidence of Kaposi sarcoma among HIV patients has significantly declined, from 60.6% in 1992 to 19.7% in 1997. The exact cause for this decline is unclear, but the introduction of protease inhibitors, combination HIV therapy, and safer sexual practices may have played significant roles.
Mortality/Morbidity
Kaposi sarcoma is linked to significant morbidity and mortality; it can disseminate to visceral organs (ie, lungs, liver, adrenal glands, kidneys, bone marrow, GI tract) and possibly cause bowel obstruction, lower extremity edema, shortness of breath, hemorrhage, and pain. Visceral and lung involvement usually portends a poor prognosis.
Generally, ophthalmic Kaposi sarcoma is indolent. Ocular tumor growth can result in severe damage to the ocular adnexa, the ocular surface, and even the orbit and choroid.
Involvement of the eyelids can cause significant disfigurement and lid dysfunction. Trichiasis can develop from mechanical ectropion or entropion. Lagophthalmos and trichiasis can result in profound irritation and dryness, infections, and corneal scarring. Large lid tumors can induce irregular corneal astigmatism. Conjunctival involvement may result in recurrent subconjunctival hemorrhages and may even be associated with squamous cell carcinoma in patients with HIV infection. Ultimately, vision could be lost from lid dysfunction, corneal surface changes, or visual obstruction.
Race
Classic Kaposi sarcoma usually involves elderly men with Mediterranean or Ashkenazi ancestry. Endemic Kaposi sarcoma usually involves young black males from central Africa.Transplant-related or AIDS-related Kaposi sarcoma has no racial predilection.
Sex
Classic Kaposi sarcoma usually involves elderly men. Endemic Kaposi sarcoma usually involves young males. AIDS-related Kaposi sarcoma predominantly involves homosexual males.
Age
Classic Kaposi sarcoma affects the older population. Endemic Kaposi sarcoma affects children with a male-to-female ratio of 1:1; after puberty, males are predominantly affected. AIDS-related Kaposi sarcoma usually affects males aged 20-49 years.
Clinical Presentation
Jacqueline Freudenthal, MD Co-Investigator, Ophthalmic Consultants Centre, Toronto
Jacqueline Freudenthal, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, Canadian Ophthalmological Society
Coauthor(s)
Kevin Ryan Yuhan, MD Attending Physician, Cornea, Cataract, Refractive and External Diseases, Southern California Permanente Medical Group
Kevin Ryan Yuhan, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Association for Research in Vision and Ophthalmology, Phi Beta Kappa, American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery
Timothy T You, MD Consulting Surgeon in Ophthalmology, Private Practice
Timothy T You, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists
Specialty Editor Board
Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Glaucoma Society
Christopher J Rapuano, MD Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital
Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Ophthalmological Society, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, International Society of Refractive Surgery, Cornea Society, Eye Bank Association of America
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, Allergan, Bausch & Lomb, Bio-Tissue, Shire, TearScience, TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Allergan, Bausch & Lomb, Bio-Tissue, TearScience.
Chief Editor
Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology
Acknowledgements
Anastasios J Kanellopoulos, MD Assistant Program Director, Clinical Associate Professor, Department of Ophthalmology, Manhattan Eye, Ear, and Throat Hospital, New York University
Anastasios J Kanellopoulos, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, Eye Bank Association of America, and International Society of Refractive Surgery
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Section of eyelid with Kaposi sarcoma lesion under high magnification. This tissue section demonstrates increased angiogenesis and spindle-shaped cells. Courtesy of Ben Glasgow, MD, University of California, Los Angeles, Department of Ophthalmology, Jules Stein Eye Institute.
Section of eyelid with Kaposi sarcoma lesion under high magnification. This tissue section demonstrates endothelium-lined vascular channels and proliferation of spindle-shaped cells. Increased angiogenesis with erythrocyte extravasation is observed. Courtesy of Ben Glasgow, MD, University of California, Los Angeles, Department of Ophthalmology, Jules Stein Eye Institute.
The inferior conjunctiva is involved more commonly than the superior conjunctiva in Kaposi sarcoma. Courtesy of Gary N Holland, MD, University of California, Los Angeles, Department of Ophthalmology, Jules Stein Eye Institute.
Kaposi sarcoma involvement of the eyelid. Courtesy of Gary N Holland, MD, University of California, Los Angeles, Department of Ophthalmology, Jules Stein Eye Institute.
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