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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 11  |  Issue : 3  |  Page : 177-180

Iatrogenic Kaposi's sarcoma unmasked by Vedolizumab in a patient with ulcerative colitis and well-controlled human immunodeficiency virus: A case report


1 Department of Internal Medicine, St. Michael's Medical Center, New York Medical College, Newark, NJ, USA
2 Department of Internal Medicine; Department of Infectious Disease, St. Michael's Medical Center, New York Medical College, Newark, NJ, USA

Date of Submission19-Jun-2020
Date of Acceptance17-Dec-2020
Date of Web Publication25-Sep-2021

Correspondence Address:
Dr. Hamid Shaaban
111 Central Avenue, Newark, NJ 07102
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJCIIS.IJCIIS_92_20

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   Abstract 


Kaposi sarcoma (KS) was first described by Moritz Kaposi as a vascular tumor that mainly involves the skin but can affect any organ system. It is typically an acquired immunodeficiency syndrome defining illness but has emerged as a neoplasm also seen in patients on immunosuppressive therapy. Few KS cases have been reported in the literature associated with inflammatory bowel diseases. We report the case of a 39-year-old male with well-controlled human immunodeficiency virus (HIV) and ulcerative colitis (UC) who presented to the hospital with new skin lesions shortly after the initiation of vedolizumab to treat his refractory UC. Immunohistochemistry of the skin lesions was consistent with Kaposi's sarcoma secondary to human herpesvirus-8. This is a rare case of iatrogenic KS in a well-controlled HIV patient secondary to immunosuppressive therapy.

Keywords: Case report, human immunodeficiency virus, Kaposi's sarcoma, ulcerative colitis, vedolizumab


How to cite this article:
Ajao SO, Jayasingam R, Shaaban H. Iatrogenic Kaposi's sarcoma unmasked by Vedolizumab in a patient with ulcerative colitis and well-controlled human immunodeficiency virus: A case report. Int J Crit Illn Inj Sci 2021;11:177-80

How to cite this URL:
Ajao SO, Jayasingam R, Shaaban H. Iatrogenic Kaposi's sarcoma unmasked by Vedolizumab in a patient with ulcerative colitis and well-controlled human immunodeficiency virus: A case report. Int J Crit Illn Inj Sci [serial online] 2021 [cited 2021 Dec 9];11:177-80. Available from: https://www.ijciis.org/text.asp?2021/11/3/177/326603




   Introduction Top


Kaposi's sarcoma (KS) is a vascular neoplasm caused by human herpesvirus-8 infection (HHV-8). It was first described in 1872 by Moritz Kaposi as a vascular tumor that mainly involves the skin but can affect any organ system.[1] The KS skin lesions go through stages. It starts as a macule in the patch stage, which then progresses into plaques in the plaque stage. It finally ends as a nodule in the tumor stage. There are four different clinical forms of KS which include classical or sporadic, endemic, human immunodeficiency virus (HIV) associated, and the iatrogenic form.[2] Iatrogenic KS was previously commonly seen after solid organ transplant but increasing cases of this form of KS have been reported in patients on immunosuppressive therapy.[1],[2] Patients with refractory inflammatory bowel diseases (IBD) are usually treated with immunosuppressive agents including steroids and more recently biologic agents, which directly target the inflammatory response pathway.[3] We report a case of a controlled HIV patient with refractory ulcerative colitis (UC) who was diagnosed with KS following initiation of vedolizumab therapy.


   Case Report Top


A 39-year-old homosexual African-American male with a past medical history of UC diagnosed 6 years earlier, condyloma acuminata, proctitis, Hodgkin's lymphoma in remission, and HIV presented to our tertiary care hospital with complaints of abdominal pain, rectal pain, and chronic bloody diarrhea. He described new tender lesions on his left medial foot which was absent at his previous admission a month ago. The lesions started as macules and later progressed tender lesions.

Mesalamine and long-term oral corticosteroids were prescribed previously for his recurrent UC flares without symptomatic relief and hence, he was also started on vedolizumab 2 months before this presentation. On physical examination, vital signs were normal. On abdominal examination, he had localized tenderness in the left lower quadrant. He also had tender cervical and inguinal lymphadenopathy. Digital rectal examination revealed bloody mucoid stool. Dermatologic examination revealed dark macules on the sole of both feet and a darkened hyperkeratotic purple-colored plaque on his left medial foot [Figure 1] and [Figure 2]. Laboratory investigation showed a white blood cell count of 12,600/mm3, erythrocyte sedimentation rate of 132 mm/h, and C-reactive protein of 4.6 mg/dL. His most recent CD4 was 873 cells/mm3 and viral load was 50 copies/mL. Colonoscopy showed severe proctitis with deep ulcerations in a continuous and circumferential pattern in the rectum with a normal sigmoid colon. Condyloma acuminata in a background of severe chronic active inflammation was also found at the anorectal junction. Histology showed severe chronic active inflammation with microabscess suggesting active UC with no evidence of spindle cells. Immunohistochemical analysis of the anal biopsy was positive for human papillomavirus (HPV) 16/18 and HPV 31/33 but negative for herpes simplex virus 1/2 and cytomegalovirus (CMV). He was managed with suppository hydrocortisone with symptomatic improvement in diarrhea and abdominal pain. Cervical lymph node biopsy was done which showed a polymorphous population of lymphocytes and was negative for malignant cells. A 4 mm punch biopsy of the left foot lesion showed atypical intradermal vascular and spindle cell proliferation. On immunohistochemistry, the spindle cells were positive for vascular markers (CD31 and CD34) and HHV-8 [Figure 3]a and [Figure 3]b. Serology was also positive for HHV-8 polymerase chain reaction with high viral titers of 74 copies/mL. The results were consistent with the diagnosis of cutaneous iatrogenic KS. The patient declined surgical treatment for his refractory UC and was continued on suppository hydrocortisone in addition to vedolizumab on discharge. Follow-up colonoscopy showed improving proctitis. The patient was also started on liposomal doxorubicin to treat KS with an improvement of his foot lesion a month later following treatment [Figure 4]. He is currently doing well.
Figure 1: Medial foot with a hyperkeratotic purple-colored plaque consistent with Kaposi's sarcoma

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Figure 2: Macules on the sole of both feet

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Figure 3: Foot skin biopsy consisting of spindle cells. (a) Spindle cells with irregular small vessel proliferation and erythrocyte extravasation between tumor cells. (b) Immunohistochemical stain showing human herpesvirus-8 expression of spindle cells

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Figure 4: Improved lesion a month later on the medial foot

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   Discussion Top


The patient in this report represents a case of cutaneous iatrogenic KS associated with HHV-8 in a well-controlled HIV patient with UC. KS is a rare diagnosis and is usually typically diagnosed when classic skin lesions are present. Although KS can occur at any time, it commonly occurs in patients with HIV with CD4 cells <200 cell/mm3, unlike in this patient.[4] KS developed in this patient, despite not having acquired immunodeficiency syndrome (AIDS), after immunosuppressive therapy to treat his underlying UC suggesting that his KS is iatrogenic. IBD is a chronic inflammation of the gastrointestinal tract and nearly 3 million males and 3.9 million females are living with IBD worldwide.[5]

Vedolizumab was approved for the treatment of both Crohn's disease (CD) and UC in 2018. It has shown efficacy and safety in patients with refractory CD and UC.[6] It is a monoclonal antibody that prevents the recruitment of lymphocytes to the inflamed tissue by blocking 4b7 integrin on the lymphocyte surface from interacting with cell adhesion molecule (MAdCAM-1) on the intestinal endothelium.[7] The 4b7 integrin is primarily expressed on a subset of memory T helper lymphocytes, and in doing so, vedolizumab inhibits lymphocyte adhesion to MAdCAM-1 which is expressed on gut endothelial cells. This reduces inflammation in gastrointestinal tissues in patients with CD and UC.[8],[9] Biologic agents have resulted in an improved quality of life and increased control of disease activity for patients with IBD. As a result of the immunosuppressive nature of these agents, they are associated with an increased risk of opportunistic infections. Majority of trials have reported a favorable safety profile of vedolizumab with a low rate of opportunistic infections or malignancies, and only few patients required discontinuation.[10] Clinical trials have infrequently reported clostridial infections, tuberculosis, and CMV infections in patients on vedolizumab for IBD.[11] Malignancies reported in patients receiving vedolizumab therapy were gastrointestinal malignancies such as colorectal cancer, hepatic cancer, appendiceal carcinoid, and peritoneal metastases.[12]

An iatrogenic form of KS has been documented in posttransplant patients and patients with a variety of diseases treated with immunosuppressive agents. Most cases of iatrogenic KS reported in the literature are in HIV negative patients.[1] Similar to our patient, there have been reported cases of cutaneous KS in patients receiving golimumab, infliximab, and adalimumab therapy.[13],[14],[15],[16],[17],[18],[19] Gastrointestinal involvement of KS has also been reported in a patient with UC exposed to Infliximab.[20]

The patient in this report received multiple immunosuppressive therapies in the form of vedolizumab and steroids. Although a number of cases suggesting the correlation between steroid and KS have been documented, our theory is that vedolizumab likely unmasked KS caused by HHV-8 in this well-controlled HIV patient with no evidence of AIDS.[1] This patient was only recently started on vedolizumab therapy, and the rapid onset of the skin lesions following initiation of therapy supports a causal relationship between the two.

Pathological diagnosis is the gold standard of diagnosis of KS. Most KS biopsies showing spindle cells are infected by HHV-8.[21] First-line treatment for iatrogenic KS consists of withdrawal or reducing immunosuppressive therapy to restore immune defenses and improve KS lesions.[22] In this patient, this mode of approach was difficult as the patient refused surgical treatment for his refractory UC. Despite the complication of KS, his UC appeared to be improving with vedolizumab on follow-up colonoscopies. Treatment of KS lesions includes chemotherapy such as liposomal doxorubicin, which was used in this patient, and paclitaxel as a second-line agent.[21]


   Conclusion Top


The iatrogenic form of KS occurs in patients on immunosuppressive therapy, as this patient. Patients with IBD on immunosuppressive drugs should be followed up closely and screened for latent viral infections before initiating therapy. This is the first report of KS unmasked by vedolizumab in a patient with well-controlled HIV disease. The case highlights that HHV-8 should be recognized as a likely underlying opportunistic infection in patients with IBD on immunosuppressive therapy. Withdrawal of immunosuppressive agents or the use of chemotherapy may be considered curative.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed.

Research quality and ethics statement

This case report did not require approval by the Institutional Review Board / Ethics Committee. The authors followed applicable EQUATOR Network (http://www.equator-network.org/) guidelines, specifically the CARE guideline, during the conduct of this research project.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Chtourou L, Ayedi L, Rejab H, Boudabous M, Mnif L, Grati A, et al. Iatrogenic colorectal Kaposi's sarcoma complicating a refractory ulcerative colitis in a human immunodeficiency negative-virus patient. Pathologica 2017;109:371-4.  Back to cited text no. 1
    
2.
Martin W III, Hood AF, Farmer ER. Kaposi sarcoma. Medicine 1993;72:245-61.  Back to cited text no. 2
    
3.
Stasi E, De Santis S, Cavalcanti E, Armentano R. Iatrogenic Kaposi sarcoma of the terminal ileum following short-term treatment with immunomodulators for Crohn disease: A case report. Medicine (Baltimore) 2019;98:e15714.  Back to cited text no. 3
    
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Temelkova I, Tronnier M, Terziev I, Wollina U, Lozev I, Goldust M, et al. A series of patients with kaposi sarcoma (mediterranean/classical type): Case presentations and short update on pathogenesis and treatment. Open Access Maced J Med Sci 2018;6:1688-93.  Back to cited text no. 4
    
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GBD 2017 Inflammatory Bowel Disease Collaborators. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2020;5:17-30.  Back to cited text no. 5
    
6.
Christensen B, Colman RJ, Micic D, Gibson PR, Goeppinger SR, Yarur A, et al. Vedolizumab as induction and maintenance for inflammatory bowel disease: 12-month effectiveness and safety. Inflamm Bowel Dis 2018;24:849-60.  Back to cited text no. 6
    
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Navaneethan U, Edminister T, Zhu X, Kommaraju K, Glover S. Vedolizumab is safe and effective in elderly patients with inflammatory bowel disease. Inflamm Bowel Dis 2017;23:E17.  Back to cited text no. 7
    
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Pijls PA, Gilissen LP. Vedolizumab is an effective alternative in inflammatory bowel disease patients with anti-TNF-alpha therapy-induced dermatological side effects. Dig Liver Dis 2016;48:1391-3.  Back to cited text no. 8
    
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Fleisher M, Marsal J, Lee SD, Frado LE, Parian A, Korelitz BI, et al. Effects of vedolizumab therapy on extraintestinal manifestations in inflammatory bowel disease. Dig Dis Sci 2018;63:825-33.  Back to cited text no. 9
    
10.
Colombel JF, Sands BE, Rutgeerts P, Sandborn W, Danese S, D'Haens G, et al. The safety of vedolizumab for ulcerative colitis and Crohn's disease. Gut 2017;66:839-51.  Back to cited text no. 10
    
11.
Ng SC, Hilmi IN, Blake A, Bhayat F, Adsul S, Khan QR, et al. Low frequency of opportunistic infections in patients receiving vedolizumab in clinical trials and post-marketing setting. Inflamm Bowel Dis 2018;24:2431-41.  Back to cited text no. 11
    
12.
Bye WA, Jairath V, Travis SPL. Systematic review: the safety of vedolizumab for the treatment of inflammatory bowel disease. Aliment Pharmacol Ther 2017;46:3-15.  Back to cited text no. 12
    
13.
Vural S, Gündoğdu M, Akay BN, Korkmaz P, Şanli H, Heper AO, et al. Aggressive kaposi's sarcoma associated with golimumab therapy. Arch Rheumatol 2018;33:384-6.  Back to cited text no. 13
    
14.
Cohen CD, Horster S, Sander CA, Bogner JR. Kaposi's sarcoma associated with tumour necrosis factor alpha neutralising therapy. Ann Rheum Dis 2003;62:684.  Back to cited text no. 14
    
15.
Francesco U, Saverio N, Valerio M, Francesco S, Rosa Daniela G. Kaposi's sarcoma in a psoriatic arthritis patient treated with infliximab. Int Immunopharmacol 2010;10:827.  Back to cited text no. 15
    
16.
Martínez-Martínez ML, Pérez-García LJ, Escario-Travesedo E, Ribera-Vaquerizo PA. Kaposi sarcoma associated with infliximab treatment. Actas Dermosifiliogr 2010;101:462-4.  Back to cited text no. 16
    
17.
Amadu V, Satta R, Montesu MA, Cottoni F. Kaposi's sarcoma associated with treatment with adalimumab. Dermatol Ther 2012;25:619-20.  Back to cited text no. 17
    
18.
Bret J, Hernandez J, Aquilina C, Zabraniecki L, Fournie B. Kaposi's disease in a patient on adalimumab for rheumatoid arthritis. Joint Bone Spine 2009;76:721-2.  Back to cited text no. 18
    
19.
Hamzaoui L, Kilani H, Bouassida M, Mahmoudi M, Chalbi E, Siai K, et al. Iatrogenic colorectal Kaposi sarcoma complicating a refractory ulcerative colitis in a human immunodeficiency negative-virus patient. Pan Afr Med J 2013;15:154.  Back to cited text no. 19
    
20.
Schneider JW, Dittmer DP. Diagnosis and treatment of kaposi sarcoma. Am J Clin Dermatol 2017;18:529-39.  Back to cited text no. 20
    
21.
Antman K., Chang Y. Kaposi's sarcoma. N Engl J Med 2000;342:1027-38.  Back to cited text no. 21
    
22.
Rios A. Kaposi sarcoma: a fresh look. AIDS 2021;35:515-6.  Back to cited text no. 22
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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