Journal of Family and Community Medicine

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 27  |  Issue : 2  |  Page : 109--113

Cherry angioma: A case–control study


Ramah I Nazer1, Rahaf H Bashihab2, Wedad H Al-Madani3, Aamir A Omair4, Mohammed I AlJasser5,  
1 Department of Medicine, Division of Dermatology, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
2 Department of Medicine, Division of Dermatology, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
3 National Center for Evidence Based Health Practice, Saudi Health Council, Riyadh, Saudi Arabia
4 Department of Medical Education, Research Unit, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
5 Department of Medicine, Division of Dermatology, College of Medicine, King Saud bin Abdulaziz University for Health Sciences; Department of Medicine, Division of Dermatology, Ministry of National Guard Health Affairs; Department of Medical Education, Research Unit, College of Medicine, King Saud bin Abdulaziz University for Health Sciences; King Abdullah International Medical Research Center, Riyadh, Saudi Arabia

Correspondence Address:
Dr. Mohammed I AlJasser
Division of Dermatology, King Saud Bin Abdulaziz University for Health Sciences, P.O. Box 3660, Riyadh 11481
Saudi Arabia

Abstract

BACKGROUND: Cherry angiomas (CAs) are very common asymptomatic vascular skin lesions. There are only a few studies on CAs in the literature and those assessing risk factors of CAs are scarce. The aim of our study was to determine risk factors for the development of CAs. MATERIALS AND METHODS: A case–control study was conducted at a tertiary care center in Riyadh, Saudi Arabia. Patients underwent a full-body examination for CAs. Demographics and other data including medical history and medications were extracted from electronic medical records. RESULTS: A total of three hundred patients were enrolled: one hundred cases with at least five CAs and two hundred controls without CAs. Bivariate analysis identified benign prostatic hyperplasia (odds ratio [OR]: = 2.591), malignancy (OR = 2.567), tamsulosin (OR = 3.171), and clopidogrel (OR = 0.321) as statistically significant associations. After multivariate logistic regression analysis, only tamsulosin (OR = 3.475, P = 0.009) and clopidogrel (OR = 0.281, P = 0.028) were found to be independent risk factors for CAs. Malignancies tended to be more associated with CAs, but this did not reach statistical significance (P = 0.07). CONCLUSION: Tamsulosin is a possible risk factor for the development of CAs. Clopidogrel seems to have a protective role preventing the development of CAs.



How to cite this article:
Nazer RI, Bashihab RH, Al-Madani WH, Omair AA, AlJasser MI. Cherry angioma: A case–control study.J Fam Community Med 2020;27:109-113


How to cite this URL:
Nazer RI, Bashihab RH, Al-Madani WH, Omair AA, AlJasser MI. Cherry angioma: A case–control study. J Fam Community Med [serial online] 2020 [cited 2020 Aug 13 ];27:109-113
Available from: http://www.jfcmonline.com/text.asp?2020/27/2/109/285817


Full Text

 Introduction



Cherry angiomas (CAs) or “Campbell de Morgan spots” are one of the most common benign cutaneous vascular lesions. They present as asymptomatic, small, bright-red papules usually on the trunk and extremities of older individuals.[1] The frequency of CAs increases with age, but have no reported clinical consequences.[2] The incidence of CAs was 49.5% in males, who seem to be more commonly affected than females.[3] The treatment of CAs is cosmetic because they are benign and asymptomatic.[1]

The pathogenesis of CAs is not entirely known. Reduced expression of miR-424 in CAs was found to be associated with abnormal angiogenesis through MEK1 or cyclin E1.[4] Human herpesvirus 8 has a possible role in eruptive CAs.[5] Some somatic genetic mutations have been identified in CAs.[6]

Risk factors associated with the development of multiple CAs could include age, chronic immunosuppression, chronic graft-versus-host disease, and malignancy.[7],[8] Some studies suggest an association between CAs and the exposure to certain chemicals and drugs such as cyclosporine,[9] sulfur mustard,[10] nitrogen mustard,[11] and bromides.[12]

Studies on risk factors associated with CAs are few and limited mainly to case reports and uncontrolled studies. Controlled studies, which explored a limited number of variables, are surprisingly very few for this common condition. This study was done to explore risk factors associated with the occurrence of CAs.

 Materials and Methods



This was a case–control study conducted at King Abdulaziz Medical City, one of the largest tertiary care centers in Riyadh, Saudi Arabia. Ethical approval was obtained from the Institutional Review Board of King Abdullah International Medical Research Center and informed written consent was obtained from all participants.

Cases were defined as patients with five or more CAs. Controls were age- and gender-matched patients who did not have any CAs. Only Saudi patients aged ≥18 years and admitted to the hospital were included in the study. Patients who refused a full body examination, or had received previous treatment for CAs, or had 1–4 CAs were excluded from the study.

The target case-to-control ratio was 1:2. The sample size was estimated as hundred cases and two hundred controls using OpenEpi sample size calculator. The calculation was based on an estimated 30%–40% exposure to the risk factor in the control group, to detect an odds ratio (OR) of 2.0 or more at the 95% confidence level and power of 80%. A nonprobability consecutive sampling was used to select the cases, while the selection of controls was based on matching for age and gender.

Full-body skin examination was performed on all patients. Variables consisted of demographics, Fitzpatrick skin phototype, and region of residence. Furthermore, the duration of CA, body site, and diameter were documented. Data regarding family history, medical conditions, malignancies, and environmental triggers were collected. Details of current medications were gathered from the electronic medical record.

Statistical analysis was done using Statistical package for the Social Sciences (SPSS) version 24 (SPSS Inc., Chicago, IL, USA). Categorical variables were presented as frequencies and percentages and were compared using the Chi-square test. Numerical variables were reported as means with standard deviation and were compared by Student's t-test. Skewed numerical data were presented as median and inter-quartile range. Step-wise multivariate logistic regression analysis was performed to determine any associated risk factors, if any, for the development of CAs. Variables entered in the model were those with P < 0.2 between cases and controls in the bivariate analysis. The results of regression analysis were presented as OR with 95% confidence interval. For all the statistical tests, P < 0.05 was considered statistically significant.

 Results



A total of hundred cases and two hundred controls were enrolled in the study. The most common site of CAs was the trunk (mainly the chest) followed by the proximal extremities, head and neck, distal extremities, hands, and feet [Figure 1]. Similarly, the trunk had the highest number and CAs with the largest diameter [Table 1].{Figure 1}{Table 1}

Patient characteristics are summarized in [Table 2]. No statistically significant difference was found between cases and controls with regard to age and gender. Similarly, no difference was found in body mass index, region of residence, job, and history of smoking. A family history of CA was positive in 12% of cases. The median duration of CAs was 6 years (interquartile range 3–20).{Table 2}

Bivariate analysis identified benign prostatic hyperplasia (OR = 2.591), malignancy (OR = 2.567), tamsulosin (OR = 3.171), and clopidogrel (OR = 0.321) as statistically significant associations [Table 3]. After multivariate logistic regression analysis, only tamsulosin and clopidogrel were found to be independent risk factors for CAs [Table 4]. Patients on tamsulosin were more likely to have CAs (OR = 3.475, P = 0.009), while those on clopidogrel seem to be less likely to have CAs (OR = 0.281, P = 0.028). Malignancy tended to have more association with CAs, but this was not statistically significant (P = 0.07).{Table 3}{Table 4}

 Discussion



Studies on CAs are generally limited. Trunk was the most common site affected with CAs in our cases, which is in agreement with the literature and clinical observation.[1] The pathogenesis of CAs is still poorly understood. Genetic factors could play a role in the development of CAs. Family history of CAs was found in 12% of our cases. Somatic mutations in GNAQ and GNA11 genes were recently identified in CAs.[6] These genes are also known to be involved in the pathogenesis of other cutaneous vascular conditions such as capillary malformations.

Controlled studies on the risk factors of CAs are scarce. Borghi et al. assessed the risk factors of eruptive CAs in a total of 1032 patients.[13] Those with eruptive CAs had ≥30 CAs. The comparative group had either no or <30 CAs. Age, immunosuppressive therapy, and malignancy were identified as independent risk factors for eruptive CAs. Malignancy in our study had a tendency of having statistically significant association with CAs., The number of CAs was significantly more on the skin of the affected breast in patients with unilateral breast cancer.[14] Serum lipids were shown to be more elevated in patients with CAs in a case–control study.[15] The lipid profile was not assessed in our study.

Tamsulosin and clopidogrel were identified in our study as independently significant associations with CAs. To the best of our knowledge, this association has not been previously reported. We found that patients on tamsulosin were more likely to have CAs. Tamsulosin is a selective alpha1A and alpha1D-adrenergic receptor blocker that is used in the treatment of BPH.[16] Alpha-1 adrenergic receptors are mainly found in the prostate and bladder. Tamsulosin works by relaxing smooth muscles in the prostate and bladder and therefore, improves urinary symptoms in patients with BPH. Although tamsulosin primarily works on the lower urinary tract, it has been shown to have some effect on the blood vessels, leading to vasodilation.[17] This might explain the association between tamsulosin and CAs found in our study.

Our findings indicate that clopidogrel seems to have a protective role against CA formation. Clopidogrel is an antiplatelet that prevents platelet aggregation through the inhibition of adenosine diphosphate.[18] It is used for the prevention of coronary artery disease and stroke. Clopidogrel has been recently shown to have an anti-angiogenic effect.[19] Both the number of microvessels and expression of vascular endothelial growth factor were significantly reduced by clopidogrel.

Our study has some limitations. Post hoc analysis showed the power of study as 60.45%, which could be due to the small sample size. The study was done at one center and therefore, its findings cannot be generalized. Another limitation is that our study design depended to some extent on patient recall of information. A better design would have been a prospective cohort but that would have been time-consuming and expensive.

 Conclusion



We identified tamsulosin as a possible risk factor for the development of CAs. However, clopidogrel seems to have a protective role, possibly preventing the development of CAs. Future well-designed studies are needed to confirm these findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Higgins JC, Maher MH, Douglas MS. Diagnosing common benign skin tumors. Am Fam Physician 2015;92:601-7.
2Luba MC, Bangs SA, Mohler AM, Stulberg DL. Common benign skin tumors. Am Fam Physician 2003;67:729-38.
3Patange VS, Fernandez RJ. A study of geriatric dermatoses. Indian J Dermatol Venereol Leprol 1995;61:206-8.
4Nakashima T, Jinnin M, Etoh T, Fukushima S, Masuguchi S, Maruo K, et al. Down-regulation of mir-424 contributes to the abnormal angiogenesis via MEK1 and cyclin E1 in senile hemangioma: Its implications to therapy. PLoS One 2010;5:e14334.
5Borghi A, Benedetti S, Corazza M, Gentili V, Ruina G, Di Luca D, et al. Detection of human herpesvirus 8 sequences in cutaneous cherry angiomas. Arch Dermatol Res 2013;305:659-64.
6Klebanov N, Lin WM, Artomov M, Shaughnessy M, Njauw CN, Bloom R, et al. Use of targeted next-generation sequencing to identify activating hot spot mutations in cherry angiomas. JAMA Dermatol 2019;155:211-5.
7Garnis S, Billick RC, Srolovitz H. Eruptive vascular tumors associated with chronic graft-versus-host disease. J Am Acad Dermatol 1984;10:918-21.
8Borghi A, Minghetti S, Battaglia Y, Corazza M. Predisposing factors for eruptive cherry angiomas: New insights from an observational study. Int J Dermatol 2016;55:e598-600.
9De Felipe I, Redondo P. Eruptive angiomas after treatment with cyclosporine in a patient with psoriasis. Arch Dermatol 1998;134:1487-8.
10Firooz A, Komeili A, Dowlati Y. Eruptive melanocytic nevi and cherry angiomas secondary to exposure to sulfur mustard gas. J Am Acad Dermatol 1999;40:646-7.
11Ma HJ, Zhao G, Shi F, Wang YX. Eruptive cherry angiomas associated with vitiligo: Provoked by topical nitrogen mustard? J Dermatol 2006;33:877-9.
12Cohen AD, Cagnano E, Vardy DA. Cherry angiomas associated with exposure to bromides. Dermatology 2001;202:52-3.
13Borghi A, Minghetti S, Battaglia Y, Corazza M. Predisposing factors for eruptive cherry angiomas: New insights from an observational study. Int J Dermatol 2016;55:e598-600.
14Guastafierro A, Verdura V, Di Pace B, Faenza M, Rubino C. The influence of breast cancer on the distribution of cherry angiomas on the anterior thoracic wall: A case series study. Dermatology 2019;235:65-70.
15Darjani A, Rafiei R, Shafaei S, Rafiei E, Eftekhari H, Alizade N, et al. Evaluation of lipid profile in patients with cherry angioma: A case-control study in Guilan, Iran. Dermatol Res Pract 2018;2018:4639248.
16Dunn CJ, Matheson A, Faulds DM. Tamsulosin: A review of its pharmacology and therapeutic efficacy in the management of lower urinary tract symptoms. Drugs Aging 2002;19:135-61.
17Harada K, Kawaguchi A, Ohmori M, Fujimura A. Antagonistic activity of tamsulosin against human vascular alpha1-adrenergic receptors. Clin Pharmacol Ther 2000;67:405-12.
18Clopidogrel. Drugs and Lactation Database (LactMed) Bethesda (MD): National Library of Medicine (US); 2006
19Luo JC, Peng YL, Chen TS, Huo TI, Hou MC, Huang HC, et al. Clopidogrel inhibits angiogenesis of gastric ulcer healing via downregulation of vascular endothelial growth factor receptor 2. J Formos Med Assoc 2016;115:764-72.