Acanthosis Nigricans as a Beacon for Hepatitis C

doi:10.21203/rs.3.rs-4949962/v1

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Case Report

Acanthosis Nigricans as a Beacon for Hepatitis C

https://doi.org/10.21203/rs.3.rs-4949962/v1

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Background: Acanthosis nigricans (AN) is a dermatological condition often associated with insulin resistance and obesity. This case report presents an unusual occurrence of AN in a non-obese patient with newly diagnosed hepatitis C virus (HCV) infection.

Case Report: A 40-year-old male presented with dark, velvety skin patches on his face, neck, axillae, and groins. Clinical and histopathological examination confirmed AN. Laboratory investigations revealed HCV infection and indicators of insulin resistance.

Conclusion: This case strengthens the previous observations and uniquely suggests a potential association between HCV infection, insulin resistance, and the development of AN, highlighting the need for further research into this relationship.

Acanthosis Nigricans

HCV

IGF-1

Hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, including numerous cutaneous disorders. While the relationship between HCV and certain skin conditions is well-established, its connection to acanthosis nigricans (AN) remains largely unexplored [1]. HCV infection is known to induce metabolic disturbances, particularly insulin resistance and hyperinsulinemia, which contributes to the development of skin manifestations [2]. This case report presents a non-obese 38-year-old male with newly diagnosed HCV infection who developed AN, suggesting a possible association between these conditions.

A 38-year-old male presented to the dermatology clinic with complaints of dark skin over his face, neck, axillae, and groins for the past 3 months. Physical examination revealed hyperpigmented velvety plaques on these areas (Figure 1A and 1B). Dermoscopy (Dermlite DL5 dermoscope) showed black dots, papillomatous projections, and cristae cutis and sulci cutis consistent with AN (Figure 2). The patient had a BMI of 23.1 kg/m2, within the normal range.

Laboratory investigations revealed elevated liver enzymes, positive HCV RNA PCR (viral load: 35,508 copies/ml), elevated serum insulin (33.2 mIU/mL), and HbA1c of 5.4%. Histopathology of a neck lesion (Haematoxylin and Eosin stain, 10x) showed hyperkeratosis, papillomatosis, and basal cell layer hyperpigmentation with mild dermal perivascular lymphomononuclear infiltrate, suggestive of AN (Figure 3).

The patient was started on metformin 500mg twice daily, glycolic acid cream, and referred to Hepatology where he was started on sofosbuvir 400mg OD and daclatasvir 60mg OD. Given the temporal relationship between AN onset and HCV diagnosis, along with evidence of insulin resistance, a possible association between HCV infection and AN was considered.

This case presents an intriguing association between HCV infection, insulin resistance, and acanthosis nigricans in a non-obese patient. Hepatitis C virus infection is known to have a wide range of extrahepatic manifestations, including various cutaneous disorders. A comprehensive review by Garcovich et al. (2015) provides a classification of cutaneous extrahepatic manifestations of chronic HCV infection (refer to Table 1), though AN is not explicitly mentioned in this classification [1].

Recent studies have highlighted an association between HCV infection and the development of skin tags, which, like AN, are linked to insulin resistance and hyperinsulinemia [2]. These metabolic disturbances are common in HCV infection. A study by Soylu S et al. (2007) found a higher prevalence of skin tags in patients with chronic HCV infection compared to healthy controls [3].

While direct evidence linking HCV to AN is limited, recent research has shed light on potential mechanisms. Insulin-like growth factor (IGF-1) is a potent stimulator of keratinocyte and fibroblast proliferation. Ferri et al. (2016) discussed how HCV infection leads to increased IGF-1 levels, which can contribute to various extrahepatic manifestations [4]. This may contribute to the development of both skin tags and potentially acanthosis nigricans.

Studies confirm HCV increases insulin resistance and type 2 diabetes risk, independent of liver fibrosis and traditional factors. HCV infection-induced insulin resistance and hyperinsulinemia can enhance IGF-1 receptor activation [5]. This metabolic disruption may indirectly contribute to the development of AN. Facial AN was found to have a positive correlation in men with metabolic syndrome [6]. A review by Niaz F et al. (2020) established the connection between insulin resistance and AN, even in non-obese individuals [7].

In our case, the patient's normal BMI but elevated insulin levels align with recent literature suggesting that HCV-induced insulin resistance may play a role in AN development. This case underscores the importance of considering underlying systemic conditions, including HCV infection, when evaluating patients with AN, particularly in those without obvious risk factors like obesity.

Understanding the relationship between HCV, IGF-1, and cutaneous manifestations provides valuable insight into the pathogenesis of various skin conditions in HCV-infected individuals. It highlights the importance of considering HCV as a potential underlying cause when evaluating patients presenting with these skin conditions, especially in the absence of other risk factors.

Further research is needed to elucidate the potential mechanisms by which HCV infection might contribute to the development of AN. Prospective studies examining the incidence of AN in HCV-infected patients could provide valuable insights into this association.

This case report adds to the growing list of cutaneous manifestations associated with Hepatitis C, emphasizing the diverse systemic effects of HCV infection and the importance of comprehensive dermatological evaluation in HCV-infected patients. We would like to suggest that acanthosis nigricans needs to be considered as a potential cutaneous manifestation of HCV infection, warranting further investigation and possible inclusion in future classifications of HCV-related skin conditions.

AN - Acanthosis Nigricans

HCV - Hepatitis C Virus

IGF-1 – Insulin-like growth factor – 1

PCR – Polymerase chain reaction

Ethics approval and consent to participate: The approval of institutional ethics committee is not required in this case and appropriate consent has been taken from the patient to publish his details and clinical images.

Consent for publication: Relevant consent has been obtained.

Competing interests: Nil

Funding: Nil

Authors' contributions:

Dr. Abe George MBBS – Primary author & Corresponding author, conceptualization, data curation, formal analysis, resources, writing – original draft & review and editing
Dr. Sumir Kumar MD – Co-author, formal analysis, resources, validation, writing – review and editing

Acknowledgements: The authors would like to thank the patient for letting us publish the details of this case report

Authors' information (optional):

Primary Author & Corresponding author: Dr. Abe George, MBBS – PG Trainee 2^nd year, Department of Dermatology, Guru Gobind Singh Medical College & Hospital, Faridkot, Punjab, India. 151203
Address: Skin OPD, 1^st floor, Guru Gobind Singh Medical College & Hospital, Faridkot, Punjab, India. 151203
Email id: [email protected]
Phone: +91 9742976987
ORCID id: 0009-0006-2498-064X
Co-author: Dr. Sumir Kumar MD, Professor & Head, Department of Dermatology, Guru Gobind Singh Medical College & Hospital, Faridkot, Punjab, India. 151203
Address: Skin OPD, 1^st floor, Guru Gobind Singh Medical College & Hospital, Faridkot, Punjab, India. 151203
Email id: [email protected]
Phone: +91 9888707940
ORCID id: 0000-0003-2130-7493

[1] Garcovich S, Garcovich M, Capizzi R, Gasbarrini A, Zocco MA. Cutaneous manifestations of hepatitis C in the era of new antiviral agents. World J Hepatol. 2015 Nov 28;7:2740-8.

[2] González-Saldivar G, Rodríguez-Gutiérrez R, Ocampo-Candiani J, González-González JG, Gómez-Flores M. Skin Manifestations of Insulin Resistance: From a Biochemical Stance to a Clinical Diagnosis and Management. Dermatol Ther (Heidelb). 2017 Mar;7:37-51.

[3] Soylu S, Gül Ü, Kiliç A. Cutaneous manifestations in patients positive for anti-hepatitis C virus antibodies. Acta dermato-venereologica. 2007 Jan 15;87:49-53.

[4] Ferri C, Ramos-Casals M, Zignego AL, Arcaini L, Roccatello D, Antonelli A, Saadoun D et al. International diagnostic guidelines for patients with HCV-related extrahepatic manifestations. A multidisciplinary expert statement. Autoimmun Rev. 2016;15:1145-60.

[5] Petta S, Macaluso FS, Craxì A. Cardiovascular diseases and HCV infection: a simple association or more? Gut. 2014;63:369-75.

[6] Panda S, Das A, Lahiri K, Chatterjee M, Padhi T, Rathi S, Dhar S, Sarma N. Facial Acanthosis Nigricans: A Morphological Marker of Metabolic Syndrome. Indian J Dermatol. 2017;62:591-7.

[7] Niaz F, Shams N, Sheikh I, Seetlani N, Ahmed N, Kamran M, Islam N, Ahmed W. Acanthosis nigricans in obese versus non-obese in a tertiary care hospital; association with BMI and central obesity. Int J Adv Res. 2021;9:10.21474/IJAR01/13050.

Table 1: Cutaneous manifestations of chronic HCV infection

Cutaneous conditions with defined epidemiological and/or pathogenetic association	Mixed cryoglobulinemia Lichen Planus Porphyria cutanea tarda
Cutaneous conditions with possible association	Pruritus (prurigo nodularis/lichen simplex chronicus) Necrolytic acral erythema
Cutaneous conditions with anecdotal association	Psoriasis Chronic urticaria Vitiligo Erythema multiforme Erythema nodosum Pyoderma gangrenosum

No competing interests reported.

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Acanthosis Nigricans as a Beacon for Hepatitis C

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