1、Review began 09/27/2021 Review ended 10/16/2021 Published 10/21/2021 Copyright 2021Costa et al. This is an open access articledistributed under the terms of the CreativeCommons Attribution License CC-BY 4.0.,which permits unrestricted use, distribution,and reproduction in any medium, providedthe ori
2、ginal author and source are credited.Kaposi Sarcoma as Presentation of HIV AClinical CaseRita Costa , Leonor Silva , Renata Monteiro , Filipa Santos , Margarida Mota 1. Internal Medicine, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, PRTCorresponding author: Rita Costa, Abstract
3、Kaposi sarcoma (KS) is the most common neoplasm of people with human immunodeficiency virus (HIV)infection. Although, in the antiretroviral therapy (ART) era, KS is a rare form of presentation ofHIV/acquired immunodeficiency syndrome. The authors present a case of disseminated KS in a 23-year-oldmal
4、e. Just after the diagnosis the patient started ART and then chemotherapy with placlitaxel with clinicalimprovement. This case is highly representative of the complexity of HIV. The authors aim to bringawareness of an unusual form of presentation of HIV, and recall the severity and the necessity of
5、an earlydiagnosis and treatment.Categories: HIV/AIDS, Infectious Disease, OncologyKeywords: opportunistic infections, cardiomyopathy, paclitaxel, haart, hiv, kaposi sarcomaIntroductionKaposi sarcoma (KS) is the most common neoplasm of patients with human immunodeficiency virus (HIV)infection 1. In t
6、he antiretrovirals era, the incidence of KS decreased from 15.2/1000 patient-year to4.9/1000 patient-year and so; nowadays, KS is an unusual presentation of HIV 2. KS is a multifocalangioproliferative neoplasm associated with the infection by human herpes virus type 8 (KSHV) 1. KSHVhas been shown to
7、 be the etiologic agent for several other tumors and diseases, including primaryeffusion lymphoma (PEL), an extracavitary variant of PEL, KS-associated diffuse large B-cell lymphoma, aform of multicentric Castleman disease (MCD), and KS inflammatory cytokine syndrome (KICS). KICS is anentity recentl
8、y described in patients with HIV and KSHV. The syndrome is characterized bylymphadenopathy, pancytopenia, and signs of systemic inflammatory syndrome 3. Lymph node, bonemarrow, or splenic biopsy can be used to distinguish from MCD 3. KICS has a higher mortality thanMCD 3.Cutaneous KS presents as red
9、, violaceous (purple), or brown lesions, from macules, patches, and papules tonodules or tumors. These lesions of the skin are highly characteristic, facilitating the diagnosis,although disseminated disease may affect any organ. The most common sites of disease disseminationinclude the skin, mucosal
10、 surfaces, respiratory tract, and lymph nodes, and extensive disseminated diseaseis often associated with lymphedema 4.KS makes a differential diagnosis with bacillary angiomatosis, nevus, and B-cell lymphoma. Biopsy is thegold standard for diagnosis 5.Case PresentationA 23-year-old male with type I
11、 diabetes resorted to an outpatient clinic complaining of disseminateddermatosis. The patient referred multiple non-pruritic skin lesions over his chest with one-year evolution,with further progression to his arms and limbs. He mentioned a significant involuntary weight loss of 15%,associated with f
12、ever predominantly in the afternoon for the last two months. He also experienced diarrheapersisting for more than two weeks. Anorexia and night sweats were denied.He had an unprotected heterosexual exposure in the past. There was no history of blood transfusion,injection drug use, or needle sharing.
13、 His only medication was insulin. On physical examination, the patient was alert, oriented but emaciated, with multiple violaceous papulesand nodules in his trunk, arms, and legs (Figure 1). Oral mucosa was not affected. He had no palpablelymphadenopathy nor splenomegaly. His vitals showed normal bl
14、ood pressure of 120/72 mmHg, sinustachycardia around 140-150 pulse per minute, and temperature of 36.5C. On lung examination, hepresented with diminished breath sounds bilaterally with no other alterations in the physical examination.Oxygen saturation on room air was 97%.1 1 1 1 1 Open Access CaseRe
15、port DOI: 10.7759/cureus.18936How to cite this articleCosta R, Silva L, Monteiro R, et al. (October 21, 2021) Kaposi Sarcoma as Presentation of HIV A Clinical Case. Cureus 13(10): e18936. DOI10.7759/cureus.18936FIGURE 1: Violaceous papulesThe lab results showed hemoglobin 9.4 g/dL, white blood cells
16、 2,770/uL, lymphocytopenia 810/uL, CD4+ Tlymphocyte count of 23 cells/mm3, normal renal function, no cytocolestase (total bilirubin 0.27 mg/dL,glutamic-oxaloacetic transaminase 23 U/L, pyruvic transaminase 13 U/L, gamma-glutamyl transferase 35U/L, and alkaline phosphatase 89 U/L), C-reactive protein
17、 1.92 mg/dL, and sedimentation velocity 67 mm/h.HIV1 serology (fourth-generation test) was positive, and the HIV viral load (VL) of 1,820,000 copies/mm3.Chest x-ray demonstrated an hypotransparency of the right lower lobe (Figure 2).2021 Costa et al. Cureus 13(10): e18936. DOI 10.7759/cureus.18936 2
18、 of 6FIGURE 2: Chest x-ray with hypotransparency of the right lower lobeA chest computed tomography (CT) showed bilateral pleural effusion and vaguely nodular areas with groundglass pattern, more evident in the right lower lobe, associated with thickening of the interlobular septa(Figure 3). These l
19、esions, considering the context, were suggestive of pulmonary KS,although lymphoma, tuberculosis, fungal infection, or other opportunistic infections could not be excluded.FIGURE 3: Thorax CT shows bilateral pleural effusion and nodularareas, with a ground glass pattern, associated with septal inter
20、lobularthickeningCT, computed tomographySkin biopsy of the lesion demonstrated dermal vascular proliferation with thin-walled and irregular vessels.Endothelial cells formed a disorganized monolayer with dissolution of collagen fibers and perianexialinfiltration. Immunohistochemistry was positive for
21、 CD34, ERG, and KSHV. These findings are compatiblewith KS skin lesions.2021 Costa et al. Cureus 13(10): e18936. DOI 10.7759/cureus.18936 3 of 6Bronchoscopy and bronchoalveolar lavage (BAL) were performed. Direct examination with gram stain andcultural examination BAL were negative for the presence
22、of bacteria. Also, cultural mycological examinationand direct examination, molecular biology, and cultural examination for mycobacterium were negative. TheBAL cytology excluded the presence of malignant cells. Pneumocystis jiroveci was also excluded by polymerasechain reaction. Although the characte
23、ristic lesions, as the violaceous lesions, were not identified onbronchoscopy and the BAL was negative for malignant cells, given the changes in the chest CT, the mostlikely diagnosis was KS with pulmonary involvement.Stool cultures were negative for parasites (Giardia and Cryptosporidium), bacteria
24、l (cultural examinationperformed for Salmonella spp, Shigella spp, Yersinia spp, Campylobacter spp, Escherichia coli O157:H7, andvibrionaceas), and Clostridiodes difficile (glutamate dehydrogenase antigen and toxin A and B screening).Colonoscopy exhibited two small ulcers on transverse colon, while
25、the biopsy revealed colorectal mucosawith colitis, positive for cytomegalovirus (CMV) (histological examination suggestive of viral inclusions byCMV, confirmed by immunohistochemistry). Histology was negative for KS and no expression of KSHV wasobserved.An ophthalmologic evaluation revealed perivasc
26、ular retinal opacification in the infero-nasal quadrant of theright eye suggestive of CMV retinitis.The patient completed 21 days of treatment with valganciclovir (900 mg twice daily) with resolution ofgastrointestinal complaints followed by secondary prophylaxis valganciclovir (900 mg once daily).S
27、oon after the diagnosis the patient started antiretroviral therapy (ART) and was proposed to chemotherapy.With that aim, he underwent a transthoracic echocardiogram that exhibited moderate mitral regurgitationand severe depression of left ventricular systolic function, with a mean ejection fraction
28、of 21%. Heunderwent Holter monitoring, which also revealed sinus tachycardia (average 118 beats per minute). Cardiacmagnetic resonance imaging (MRI) showed dilated cardiomyopathy (non-ischemic etiology) with severeimpairment of biventricular systolic function, and intramural fibrosis at the level of
29、 the basal and middlesegments of the interventricular septum - stria mesocardial. The fibrosis pattern described can be found inthe context of post-myocarditis, familial or idiopathic etiology, and associated with poor prognosis.Although the patient had no family history of sudden cardiac death, syn
30、cope, or left ventricular hypertrophy,genetic testing for cardiomyopathies was performed and confirmed the suspicion of hereditarycardiomyopathy (the c.43009del p. variant of the TNN gene, in heterozygosity; and the c.4046GA variant inthe DSP gene, of uncertain significance). He was initiated on pro
31、gnostic modifying therapy for heart failure(as angiotensin receptor-neprilysin inhibitor, beta blocker, and aldosterone receptor antagonist).At this point, it is not clear whether the heart failure is explained by the HIV involvement of the heart or thepresence of hereditary cardiomyopathy. The echo
32、cardiogram was repeated after four months and revealed agreat improvement, already with normal left ventricular systolic function.The patient was treated with paclitaxel (100 mg/m2, every 15 days), and after six cycles he presented withpartial response with a great improvement of the lung lesions an
33、d was kept in the same chemotherapyscheme. Five months after ART (darunavir 800 mg plus cobicistat 150 mg, emtricitabine 200 mg,and tenofovir alafenamide) and chemotherapy the patient still has countless violaceous lesions on the trunkand upper limbs, now more tenuous and without relief. The patient
34、 has HIV VL of 45 copies/mL and 38 CD4+T cells.DiscussionThe clinical manifestations in our patient highlight the potentially aggressive course of KS in people livingwith HIV (PLWH). The disseminated presentation of acquired immunodeficiency syndrome (AIDS)-associated KS has a poor prognosis 3. Pulm
35、onary involvement generally occurs in severelyimmunosuppressed patients who already have mucocutaneous or digestive involvement, though 15% ofpatients with pulmonary KS have no mucocutaneous lesions at diagnosis 6.Pulmonary involvement is particularly important, as it is associated with worse progno
36、sis and increasedmortality compared with other systems 7. In a cohort of 305 HIV-1-infected patients diagnosed with KSsince 1996, the median survival time for patients with pulmonary KS was 19 months compared with amedian survival time of four months reported for the same cohort in the pre-ART era 8
37、.Given the frequency of opportunistic pulmonary infections in PLWH, diagnosing lung involvement is often achallenge. Even bronchoscopy may fail to establish the diagnosis. Mitchell and Miller reported that only 45%of cases have endobronchial lesions located at segmental orifices in the main trachea
38、or bronchi that arereachable with a bronchoscope 9. In pre-ART era, the estimated incidence of pulmonary KS in patientsliving with AIDS was around 30% 10.According to AIDS Clinical Trials Group system for AIDS-related KS, patients are assessed on the extent oftumor (T), the status of the immune syst
39、em (I), and the presence of systemic illness (S). In the era of ART,2021 Costa et al. Cureus 13(10): e18936. DOI 10.7759/cureus.18936 4 of 6CD4 level does not seem to provide prognostic information. Two different risk categories were identified: agood risk (T0S0, T1S0, T0S1) and a poor risk (T1S1).
40、Our patient presented with high-risk factors: widespreadKS lesions (T1) and systemic illness (opportunistic infection and B symptoms - as fever, night sweats, andsignificant weight loss).Currently, there is no cure for KS; therefore, the aim of the therapy is to slow disease progression andalleviate
41、 symptoms. Therapeutic options depend on the extent and rate of tumor growth, VL, and CD4+ Tlymphocyte count. Localized skin disease can be treated with ART and some local therapies (laser CO2,cryotherapy, radiotherapy, intralesional vinblastine) 11. There are no defined criteria for systemic KSther
42、apy, and the decision should be individualized. Systemic KS therapy is usually administered to patientswith widespread T1 disease, extensive cutaneous KS, symptomatic or life-threatening visceral KS, ulceratingKS, KS associated with edema, or tumor-related pain 12. Also, systemic therapy is justifie
43、d in patients thatfail to respond to ART 12. A 2014 review suggested that ART plus chemotherapy may be beneficial inreducing disease progression compared to ART alone in patients with severe or progressive KS 13.Cytotoxic chemotherapy represents the standard of care, and liposomal formulations of do
44、xorubicin ordaunorubicin and paclitaxel show similar clinical efficacy 13,14. However, KSHV cannot be eradicated;tumors may recur and patients often require additional therapies. Chronic administration of cytotoxic agentsis poorly tolerated, and in this setting, drugs such as pomalidomide/lenalidomi
45、de may be discussed 11.Importantly, patients co-infected with KS and HIV often develop more than one KSHV-associateddisease. Active KSHV replication has also been associated with KICS. The clinical presentation mimics sepsiswith respiratory failure and often leading to mechanical ventilation and vas
46、opressor use. However, thesepatients do not improve with standard antibiotic therapy. It occurs due to overproduction of KSHV-relatedinterleukins (IL-6 and IL-10) and symptoms are from the associated cytokine storm. Although there is noestablished gold standard of treatment, addition of immunomodula
47、tory therapy such as rituximab to theongoing ART has been shown to result in improvement in clinical status. KICS has a high mortality rate ifleft untreated and early recognition and management is important to improve patient outcomes. It has beenhypothesized that treating the underlying tumor may d
48、ecrease KSHV-associated cytokines. However, insituations where this syndrome is present, treating the original sarcoma is not easy due to relatedcomorbidities. Another drug that may be used is ganciclovir, which has activity against KSHV. Finally,liposomal doxorubicin can be used to eliminate KS spi
49、ndle cells and prevent the aggressive proliferation ofKS lesions with concurrent rituximab treatment 15.ConclusionsThe risk of AIDS-related KS has declined since the introduction of ART in the mid-1990s. However, itremains highly prevalent in PLWH and can arise at any time during the course of HIV i
50、nfection. It acceleratesthe clinical course of HIV infection, and generally occurs at CD4 count 200 cells/mm3. Response totreatment is variable according to lesion extension and patient immunity status. It is now appreciated that KSHV can cause several diseases, several of which had not been previou
