Flat Warts (Verrucae Planae) Confined to the Pigment of a Tattoo: A Rare Tattoo-associated Complication.

Tattoos are a form of decorative body art in which pigment dyes of different colors are inoculated into the skin. It is estimated that 15-25% of general population has one or more tattoos (1), and the reasons for the popularity of this procedure may include greater social acceptance, aesthetic appeal, or perhaps the option of using laser removal techniques to eliminate unwanted tattoos. Even though modern professional tattoos are usually performed in sterile conditions, complications still occur, and with increasing numbers of people getting tattoos, the incidence of tattoo-associated side-effects presenting to dermatologists, which may be as high as 2%, is likely to increase (2). Herein we present a case of a 43-year-old male patient with multiple HPV-associated flat warts (verrucae planae) confined to the black pigment of a tattoo done 15 years ago. A 43-year-old patient presented to our clinic due to eczema on the trunk. However, during skin examination, we observed asymptomatic verrucous papules confined to the black ink of a tattoo done 15 years ago on the lateral side of his right lower leg (Figure 1a). Clinical examination showed multiple, discrete, skin-colored, verrucous papules disseminated exclusively within the lines of the black-colored tattoo. Full skin examination did not reveal any similar lesions anywhere else on the body. Dermoscopically, papules showed a discretely papillomatous surface and sharp borders (Figure 1b). The patient had another black tattoo on his trunk, in which no similar lesions were found. All his tattoos had been done more than 15 years ago in a professional tattoo salon and with no previous history of cutaneous lesions within tattoos. The patient had no other medical conditions and was not taking any medications. Additionally, no history of warts or other HPV-related lesions of the skin or mucosal membranes could be established. A biopsy of an individual papule was taken and sent for a histopathological analysis, which subsequently showed hyperkeratotic, orthokeratotic, and parakeratotic acanthotic epidermis with hypergranulosis and rare cells with perinuclear halo indicative of koilocytes (Figure 3b). Immunohistochemical analysis showed negative reaction for p16 and p53, while Ki67 was positive only in rare basal and suprabasal cells. These findings were indicative of low-risk HPV, and the diagnosis of HPV-induced verruca plana was ultimately established. The patient was then successfully treated with cautious curettage of the lesions, leaving no scars. Due to the growing popularity of tattoos, especially among younger populations, it is necessary to emphasize the possibility of various tattoo-related side-effects that can still occur due to improper preparation of the tattoo location, contamination of ink products, improperly sterilized instruments, or due to insufficient personal hygiene following tattooing (3). In the past, tattoo-associated infections were significantly more frequent, with the highest prevalence of Staphylococcus and Streptococcus infections causing impetigo, folliculitis, cellulitis, erysipelas, or sepsis (2), but recent improvement and efforts in using sterile techniques in tattooing has led to a significant drop in the number of tattoo-related infections. In this short report, we present a case of a different and a relatively rare type of tattoo-associated infection - flat warts i.e., verrucae planae. Flat warts are usually caused by HPV-3, -6B, -10, -28, and -49. Typical predilection sites are the face, dorsal sides of the hands or feet, arms, and legs, and they usually appear as skin-colored, pink, or brown, flat-topped discrete papules. It is believed that HPV can be inoculated through contaminated ink, instruments, the artist's saliva, or that it may be a pre-existing unnoticed wart in the tattooed area (4-6). The latency period between tattooing and HPV infection can range from several months to 10 years, with a mean period of 5 years (3). This may suggest that the immune system can control the infection for some time, and that some form of immune suppression may result in the development of a clinical disease. In our case, the latency period could not be established due to the patient's unawareness of the lesions, and no potential trigger could be identified. The occurrence of lesions on only one of the patient's tattoos as well as their confinement to the black pigmented ink may indicate a correlation to this specific pigment. Ramey et al. (6) conducted a study in which they assessed the localization of warts in differently colored tattoos. The results showed that black ink tattoos had a seven times higher risk of developing warts when compared with colored ink. At first it was thought that this was due to HPV inoculation via contaminated instruments, ink, or autoinoculation of the patient's own warts, but some evidence indicates that it is unlikely for HPV to survive in ink and that if the warts were inoculated they would occur equally in all ink colors. A different theory by Ruocco et al. (7) explains this phenomenon through an "immunocompromised district" mechanism, in which polycyclic aromatic hydrocarbons found in black ink produce reactive oxygen species (ROS) that can damage cellular structures and consequently increase the risk of a variety of infections, including HPV. Moreover, black ink contains almost pure nanoparticles, which are associated with greater ROS production than the larger particles found in colored ink (7,8). There are several treatment options for verrucae planae, such as liquid nitrogen cryotherapy, topical 5% fluorouracil, topical 5% imiquimod, 0.025-0.050% tretinoin, 10% salicylic acid, or 10-30% glycolic acid. These treatments have differing success rates. Destructive modalities, such as surgical excision, curetting, or laser ablation may significantly damage the tattoo and cause scarring, and are thus not regularly performed. It's necessary to emphasize that despite today's sterile methods of tattooing, complications may still occur and medical professionals, namely dermatologists, should be aware of them. A person who wishes to get a tattoo should be advised to visit a licensed tattoo artist at a licensed tattoo parlour only. Patients with pre-existing dermatoses characterized by an isomorphic phenomenon, such as psoriasis or lichen planus, are particularly prone to developing a tattoo-associated adverse reaction, and those with severe dermatoses should be advised to avoid tattooing. Additionally, people with a previous history of warts should be aware of the possibility of warts occurrence, even years or decades after tattooing. Even though most of tattoo-related side effects are merely inconveniences, there is a potential for serious complications and patients should be advised as such.

Segmental Erythema Multiforme: An Unusual Drug Reaction to Anastrozole.

Erythema multiforme (EM) is an immune-mediated, mucocutaneous hypersensitivity syndrome that can occur as a result of various medications, including a wide range of antineoplastic and hormonal drugs. Anastrozole, a nonselective aromatase inhibitor used in breast cancer management has been associated with different cutaneous side effects, of which EM is rarely seen and usually in a minor or major form with typical target lesions. This is a short report of a patient who developed a rare cutaneous side effect after the use of aromatase inhibitor anastrozole - segmental erythema multiforme in cancer-affected area. Cutaneous adverse effects limited to cancer-affected breast are extremely rare but should be considered in everyday dermatological practice. We find this case instructive not only because of the rarity of the segmental EM, but also because, contrary to classical teaching, drug eruption due to anastrozole occurred months, not days after the initiation of therapy.

Brentuximab-induced splinter nail haemorrhages in a patient with Sézary syndrome: A case report.

Sézary syndrome is a systemic variant of cutaneous T-cell lymphoma characterized by erythroderma, lymphadenopathy and circulating atypical lymphocytes (Sézary cells). It may present with nonspecific lesions on multiple digits. We describe an atypical case of brentuximab-induced splinter nail haemorrhages in a patient with Sézary syndrome, associated with a poor prognosis during follow-up. Concomitantly with the appearance of nail lesions, significant lymphocytosis was detected as well as infiltration of bone marrow and nail matrices. The lesions followed a precise sequence, which can be traced back to the monthly application of brentuximab and its direct cytotoxic effect on CD30+ T lymphocytes in the nail matrix. Brentuximab-induced nail lesions might be associated with decreased efficacy of brentuximab in this patient with advanced cutaneous T-cell lymphoma.

A Reminder of Skin Cancer During the COVID-19 Pandemic.

The year 2020 has been marked by the coronavirus disease 2019 (COVID-19) pandemic, caused by an RNA virus called SARS-COV2 (severe acute respiratory syndrome coronavirus). The fight against this epidemic has become the center of our daily clinical practice as well as of our private lives, in which avoiding infection has become one of our most important goals. Even though COVID-19 is a potentially lethal disease, especially for the elderly and people with chronic diseases, it did not cause all the other life-threatening diseases to vanish. On the contrary, many scheduled medical activities and procedures, especially preventive and non-urgent internal and surgical activities, had to be postponed due to COVID-19 crisis. This interruption in the health care system can negatively affect the diagnosis and management of our patients with other health issues, namely malignant skin tumors, of which melanoma is the most aggressive. In this letter, we as dermatovenereologists from the Croatian Referral Centre of The Ministry of Health for Melanoma needed to express our concern regarding the increasing number of patients with delayed diagnosis of skin cancer, with special emphasis on melanoma detection and treatment. In the last few months, a large number of our newly-diagnosed patients with melanoma, as well as those with non-melanoma skin cancers, reported that they had noticed a suspicious skin lesion a few months ago but decided not to seek help from dermatologist due to the worrisome epidemiologic situation. In the current environment, clinical skin examination may be viewed as less important and thus postponed, but neglecting melanoma throughout the virus outbreak may lead to increased rates of morbidity, mortality, and consequently a greater financial burden for the health system (1). There are several reasons for such a relaxed attitude towards skin health in our patients. Unlike cardiac, pulmonary, or digestive difficulties, which patients consider life-threatening and for which they seek emergency care despite the coronavirus pandemic, skin tumors do not cause great subjective or significantly noticeable objective symptoms. Moreover, all of the skin tumors and especially melanoma , mostly present as small changes of just a few millimeters in diameter in the early stage at which they are prognostically most favorable. For the average person with no medical education, such small lesions usually do not cause any concern as they have no awareness of the fact that small and inconspicuous skin lesions may be dangerous and potentially even lethal. According to the recommendations concerning patient management during COVID-19 pandemic, oncological examinations should still be performed regularly (2). In spite of that, the cancelation of appointments, especially by patients who are being monitored for high-risk lesions, is inevitable when COVID-19 is disrupting everyone's lives. With the pandemic evolving and no clear solutions in sight, now is the time to emphasize the importance of self-examination and teledermatology in early melanoma diagnosis. Even though diagnosing and managing pigmented skin lesions usually requires face-to-face examinations and dermoscopy as a crucial tool in early melanoma detection, in these times, and especially for people with a higher risk of SARS-COV2 infection, remote communication could prevent delays resulting in worse prognosis and could also eliminate the risk of infecting healthcare workers. Moreover, teledermatology can also be initiated by doctors asking patients to monitor lesions between clinical visits (3). However, we should not rely solely on this technology but should instead assess every patient individually and insist on a face-to-face examination for those at greater risk, with the aim that, if necessary, surgery be performed in timely manner. The collaboration between general practitioners and dermatologists represents an important aspect of achieving the most rational and effective health care in terms of performing triage of patients who can be assessed by teledermatology as well as referring to hospital centers those who need face-to-face examination and further treatment. During the first breakout of the epidemic in March 2020, the multidisciplinary team for melanoma from the Croatian National Referral Melanoma Centre provided recommendations for the management of patients with melanoma during COVID epidemic, designed according to the guidelines of the National Comprehensive Cancer Network (NCCN) (4) and considering the specifics of health care and clinical practice in the Republic of Croatia. Due to epidemic circumstances, preventive actions such as Euromelanoma and many other campaigns that included massive preventive skin examinations of the population and which were conducted for years by Croatian dermatologists throughout the country, could not be organized this year. This is particularly worrisome because on average about 800 patients are diagnosed with melanoma annually in Croatia, of which 60 during public health preventive actions. Despite these circumstances, we were able to maintain public awareness of the importance of early skin cancer recognition by sending the message through different media such as newspapers, television, and social media (Facebook and Instagram). We find that now more than ever it is essential to remind and teach the population about the importance of regular monthly skin self-examinations and recognition of atypical lesions. Clearly, a thorough dermatological examination includes full skin examination from head to toe. Herein we would also like to remind our readers that most skin cancers develop in the head and neck area, which is the most UV-exposed part of the body. Therefore, despite the epidemic conditions, the removal of patients' masks and thorough inspection of the face is mandatory. We find it most practical and efficient to perform the body and scalp examination first, followed by the face examination after the patient gets dressed. Prior to removal of the mask, we ask the patient not to talk during close examination. Even though this could make dermoscopic examination harder to perform, we strongly suggest wearing a protective shield and mask during close examination whenever possible. Between patients, the examining room should be disinfected and ventilated. As doctors, we live in uncertain times when we are heavily burdened by the currently unstoppable COVID epidemic, always awaiting new instructions from the state administration every day and wondering whether perhaps tomorrow we dermatologists will be assigned solely to the service of patients with COVID-19. In the end, we would like to once again remind you that despite the ravaging COVID pandemic and all the epidemiological measures that come with it, other diseases still exist. It is expected of us to draw attention to the still growing incidence of skin cancers and the serious consequences that can occur as a result of a delayed diagnosis.

Dermoscopic Features as Predictors of BRAF Mutational Status and Sentinel Lymph Node Positivity in Primary Cutaneous Melanoma.

Dermoscopy is a diagnostic tool widely used in clinical practice for the detection of skin tumors, especially early stages of melanoma. Recent studies have shown that different dermoscopic features are associated with important prognostic parameters of melanoma, such as BRAF mutational status and sentinel lymph node status. More than half of all melanomas harbor a mutation in the BRAF oncogene. The current management of advanced-stage melanomas is greatly determined by the presence or absence of a mutation in this gene, as targeted therapy with BRAF kinase inhibitors is one of the first therapeutic choices for these patients. Sentinel lymph node status is one of the most significant predictors of a melanoma patient's survival. Recent studies have shown that different dermoscopic patterns are also associated with sentinel lymph node status. This short article reviews studies that investigated correlations between dermoscopic features, BRAF mutation status and sentinel lymph node status.