Intralesional Antigen Immunotherapy in the Treatment of Periungual Warts.

BACKGROUND: Intralesional immunotherapy using different types of antigens is considered an effective and safe treatment option for different types of warts. However, there are few studies that illustrate the use of these antigens in the treatment of periungual warts as a distinct type of warts. OBJECTIVE: To evaluate the efficacy and safety of three antigens: measles, mumps, rubella (MMR) vaccine, Candida antigen, and purified protein derivative (PPD) in the treatment of periungual warts. METHODS: The study included 150 patients who were randomly assigned to 3 groups with 50 patients in each. Each agent was injected intralesionally at a dose of 0.1 mL into the largest wart at 2-week intervals until complete clearance or for a maximum of 5 sessions. RESULTS: Complete clearance of warts was observed in 70%, 80%, and 74% in PPD, Candida antigen, and MMR vaccine groups, respectively. There was no statistically significant difference regarding the therapeutic response between the 3 studied groups. Adverse effects were transient and insignificant in the 3 groups. No recurrence of the lesions was reported in any of the studied groups. CONCLUSIONS: Intralesional antigen immunotherapy seems to be an effective therapeutic option for the treatment of periungual warts.

Polydactylous Squamous Cell Carcinoma of the Nail Unit: A Structured Review of the Literature.

Squamous cell carcinoma of the nail unit (SCCNU) is a rare neoplastic condition that involves multiple digits (polydactylous SCCNU) in only 3.9% of cases. Here, we report a case of polydactylous SCCNU and perform a comprehensive review of MEDLINE and Embase to collate 44 cases of polydactylous SCCNU reported to date. Polydactylous patients were younger on average (48 to 61-63 years) and had a longer diagnostic delay (44 vs 35.1 months) compared with reported monodactylous cases. Human papillomavirus (HPV) positivity was observed in 49% of cases, and the most common serotypes noted were 16 (25.8%), 73 (16.1%), 58 (9.7%), 18 (6.5%), and 33 (6.5%). Twenty percent of the cases were in immunosuppressed individuals who had a statistically significant lower age at diagnosis (39.33 years vs 51.12 years; P = .01) and diagnostic delay (2.50 months vs 132.46 months, P = .04). Patients with HPV positivity had a lower age at diagnosis (43.74 years vs 53.29 years, P = .04). Environmental exposures noted to be associated with polydactylous disease included X-rays, paint/solvents, soluble oils, and stagnant water. This comprehensive literature review serves to characterize polydactylous SCCNU and distinguish the differences in its characteristics to improve diagnosis and clinical recognition.

Nail squamous cell carcinoma: A hidden high-risk human papillomavirus reservoir for sexually transmitted infections.

Human papillomavirus (HPV) causes cervical cancer, anal cancer, vulvar cancer, vaginal cancer, penile cancer, and oropharyngeal cancer. Squamous cell carcinoma (SCC) in the genital region in particular is recognized to be caused by HPV infection, and intraepithelial lesions of the penis and vulva are termed penile intraepithelial neoplasia and vulvar intraepithelial neoplasia, respectively. Although SCC of the nail apparatus is recognized as being associated with high-risk HPVs, it is not well-known in general medicine, and its analysis has been insufficient. In this article, we reviewed 136 cases of HPV-associated nail SCC and SCC in situ and delineated their clinical characteristics. We found that half of the cases were high-risk HPV-associated. Almost all of the types were high-risk α-HPVs. This disease had a male dominance and left hand digit 3 and right hand digits 1-3 were typically affected. In this review, 24% of the cases of nail SCC had a history of other HPV-associated diseases, suggesting the possibility of genitodigital transmission. We propose that nail SCC is a hidden high-risk HPV-associated reservoir and should be recognized as a sexually transmitted infection.

Bowen disease of the nail unit: a retrospective study of 12 cases and their association with human papillomaviruses.

BACKGROUND: Bowen disease is the most frequent nail malignancy, usually seen as a verrucous plaque of the nail in men. OBJECTIVE: To characterize the affected patient population, the clinical manifestations, the diagnostic delay and diagnostic steps, and presence of human papilloma virus (HPV) infection. METHODS: We retrospectively evaluated all cases of Bowen disease of the nail unit over a period of 9 years. Data were obtained from our electronic database. Human papilloma virus genotype was assessed in biopsy specimens by polymerase chain reaction (PCR) sequencing. RESULTS: We identified 12 cases of Bowen disease of the nail unit in 10 patients. Mean age at onset was 52 years, with a male predominance of 90%. The thumb and middle finger were the most frequently affected (66%). Fifty percent of the lesions presented as periungual and subungual verrucous tumours. Patients sought medical evaluation after a mean delay of 5.7 years; histopathological diagnosis was made after a mean delay of 3.2 years. HPV infection was identified in 75% of the cases. CONCLUSIONS: Any recently appeared verrucous lesion of the nail unit in men above the age of 40 years should raise the suspicion of Bowen disease and lead to further histopathological diagnostic procedures.

Hand-foot-and-mouth disease: a new look at a classic viral rash.

PURPOSE OF REVIEW: Hand-foot-and-mouth disease (HFMD) is a common cause of viral rash in children with classic skin findings which are easily recognized by pediatricians. Recently, several atypical cutaneous manifestations of HFMD have been described. Awareness of these patterns may lead providers to appropriate diagnosis and management. This review also highlights the epidemiological patterns of more virulent strains and emerging research in disease prevention. RECENT FINDINGS: Classic HFMD presents with tender lesions on the hands, feet, and oral mucosa. Atypical skin findings in HFMD may be seen in children with atopic dermatitis. These include 'eczema coxsackium', in which eczematous skin is superinfected with coxsackie virus, resembling herpes infection. Nail changes, such as shedding, may follow HFMD after a latency period. Enterovirus 71 is responsible for epidemic outbreaks of HFMD in Asia, with systemic manifestations and occasionally neurological sequelae. Research is underway to develop a vaccine which could curb epidemics, but for the present, supportive care and hygiene measures are the standard of care. SUMMARY: Atypical manifestations of HFMD in children with atopic dermatitis may mimic herpetic superinfection. In a child presenting with nail changes, consider antecedent HFMD in the differential diagnosis. The mainstay of treatment for HMFD remains supportive care.

Successful treatment of periungual warts with topical cidofovir.

Periungual warts represent a treatment challenge because of its high recurrence rate and recalcitrance. These are benign lesions produced by the human papilloma virus (HPV) that often do not respond to habitual treatment. Cidofovir is a potent antiviral drug that acts inactivating viral DNA polymerase. Topical cidofovir for the treatment of HPV-related cutaneous and mucous lesions is becoming increasingly common. Our aim was to assess the efficacy and safety of cidofovir cream for the treatment of viral periungual warts. We undertook a retrospective observational study of patients with periungual warts who received treatment with topical cidofovir between January 2010 and December 2013 at the Dermatology Service of the Hospital Costa del Sol, Marbella, Spain. Data were recorded about the rate of treatment response, the adverse effects and recurrences, as well as the characteristics of the patient cohort. We identified 41 patients who had received some previous treatment. The concentration of cidofovir was 3% in all cases, usually applied twice a day (in 37 of the 41 cases). A greater or lesser response was noted in 35 cases. There were six recurrences in the follow-up period. Topical cidofovir seems to be a useful alternative for the therapeutic management of recalcitrant periungual common warts that fail to respond to usual treatment. Our experience with the use of this antiviral agent has been satisfactory, although in our opinion, it should be reserved for specific cases as its economical cost represents an important limitation.

Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling.

Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/ß-catenin signaling by restraining LDL receptor-related protein 6 (LRP6) phosphorylation and ß-catenin accumulation and lead to onychomadesis. Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3ß inhibitor) CHIR99021 can restore nail stem cell differentiation and protect against nail shedding. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.

Onychomadesis in two sisters induced by varicella infection.

Onychomadesis is separation of the nail plate from the nail matrix due to arrest of nail growth for a certain period. Here we describe two patients with onychomadesis on the hands after varicella infection. To our knowledge, this is the first case of onychomadesis reported after varicella infection.

Onychomadesis following childhood hand-foot-mouth disease in two pairs of siblings- a familial predisposition?

Onychomadesis is presented in four patients as a result of hand-foot-mouth disease.

Enterovirus co-infections and onychomadesis after hand, foot, and mouth disease, Spain, 2008.

Hand, foot, and mouth disease (HFMD), a common disease caused by enteroviruses (EVs), usually affects children. Clustered and sporadic HFMD cases, followed by onychomadesis (nail shedding), occurred during summer and fall 2008 in Valencia, Spain. Fecal samples from onychomadesis patients, who did or did not have previous HFMD, and from healthy children exposed to onychomadesis patients tested positive for EV. The complete viral protein 1 capsid gene sequence was obtained for typing and phylogenetic analysis. Two EV serotypes, coxsackievirus A10 and coxsackievirus B1 (CVB1), were mainly detected as a monoinfection or co-infection in a childcare center where an onychomadesis outbreak occurred. On the basis of our results, and detection of CVB1 in 2 other contemporary onychomadesis outbreaks in childcare centers in Spain, we propose that mixed infection of an EV serotype that causes HFMD, plus the serotype CVB1, could explain the emergence after HFMD of onychomadesis, a rare and late complication.

An outbreak of coxsackievirus A6 hand, foot, and mouth disease associated with onychomadesis in Taiwan, 2010.

BACKGROUND: In 2010, an outbreak of coxsackievirus A6 (CA6) hand, foot and mouth disease (HFMD) occurred in Taiwan and some patients presented with onychomadesis and desquamation following HFMD. Therefore, we performed an epidemiological and molecular investigation to elucidate the characteristics of this outbreak. METHODS: Patients who had HFMD with positive enterovirus isolation results were enrolled. We performed a telephone interview with enrolled patients or their caregivers to collect information concerning symptoms, treatments, the presence of desquamation, and the presence of nail abnormalities. The serotypes of the enterovirus isolates were determined using indirect immunofluorescence assays. The VP1 gene was sequenced and the phylogenetic tree for the current CA6 strains in 2010, 52 previous CA6 strains isolated in Taiwan from 1998 through 2009, along with 8 reference sequences from other countries was constructed using the neighbor-joining command in MEGA software. RESULTS: Of the 130 patients with laboratory-confirmed CA6 infection, some patients with CA6 infection also had eruptions around the perioral area (28, 22%), the trunk and/or the neck (39, 30%) and generalized skin eruptions (6, 5%) in addition to the typical presentation of skin eruptions on the hands, feet, and mouths. Sixty-six (51%) CA6 patients experienced desquamation of palms and soles after the infection episode and 48 (37%) CA6 patients developed onychomadesis, which only occurred in 7 (5%) of 145 cases with non-CA6 enterovirus infection (p < 0.001). The sequences of viral protein 1 of CA6 in 2010 differ from those found in Taiwan before 2010, but are similar to those found in patients in Finland in 2008. CONCLUSIONS: HFMD patients with CA6 infection experienced symptoms targeting a broader spectrum of skin sites and more profound tissue destruction, i.e., desquamation and nail abnormalities.

Ungual and periungual human papillomavirus-associated squamous cell carcinoma: a review.

BACKGROUND: Human papillomavirus (HPV)-associated squamous cell carcinoma (SCC) and SCC in situ are often reported in the genital region. The association of HPV with SCC in the ungual and periungual skin is less well recognized, and verrucous lesions may undergo years of therapeutic attempts without a diagnostic biopsy. OBJECTIVES: To review the epidemiology, associations, and role of HPV in digital SCC and SCC in situ. METHODS: The English-language literature reporting HPV-associated SCC and SCC in situ of the digits was reviewed. RESULTS: HPV-associated SCC and SCC in situ were almost equally represented. The patients' ages ranged from 22 to 89 years, with men affected twice as often as women. HPV16 was the most common subtype. The tumors presented as persistent verrucae, present for an average of 5.3 years. Immune suppression was documented in only 6.8% of patients. Approximately 6% of cases required digital amputation. LIMITATIONS: Most of the information was obtained from case reports, some of which had limited data regarding the exact location of the tumor and the diagnostic and treatment course. HPV subtyping is not commonly performed in these tumors, which limited the number of reports that could be evaluated. CONCLUSIONS: The majority of digital HPV-associated SCCs or SCCs in situ involves the nailbed region. The clinical appearance is most commonly that of a periungual verruca. Tumors have a higher rate of recurrence after excision than SCC in other sites. Periungual and subungual warts caused by high-risk HPV subtypes pose a risk for malignant transformation in both immunocompetent and immunocompromised hosts.

High-risk human papillomavirus infection in Bowen's disease of the nail unit: report of three cases and review of the literature.

BACKGROUND: Bowen's disease (BD) of the nail unit is associated with human papillomavirus (HPV) infection. OBJECTIVE: This study aimed to investigate the frequency of high-risk HPV infection, gender, age and digital distribution in this condition. METHODS: Biopsy specimens of 3 consecutive cases with periungual BD were investigated for the presence of HPV DNA by in situ hybridization and by polymerase chain reaction (PCR). Furthermore, 74 cases of ungual BD conducted with HPV genotyping as reported in the literature were reviewed. RESULTS: PCR of biopsy specimens revealed in 2 cases infection with HPV-16 and in 1 case with HPV-73. Additionally, in 1 HPV-16-positive case HPV-31/33 was detected by in situ hybridization. In line, review of the literature demonstrated a clear association of HPV-positive BD with high-risk HPV types. Interestingly, age at diagnosis was significantly lower in women. Whereas in both genders the second to fourth fingers on both hands were commonly diseased, only in men the thumbs were also prominently affected. CONCLUSIONS: Infection with high-risk HPV types is common in BD of the nail unit suggesting the aetiological cause. Therefore, patients and partners should be closely followed up for digital and genital HPV-associated lesions.

Onychomadesis outbreak in Valencia, Spain associated with hand, foot, and mouth disease caused by enteroviruses.

This report evaluates the June 2008 onychomadesis outbreak in Valencia, Spain. The study sample consisted of 221 onychomadesis cases and 77 nonaffected individuals who lived close to those affected. We collected data on dietary variables, hygiene products, and individual pathological histories. Feces and blood specimens were collected from 44 cases and 24 controls to evaluate exposure to infectious agents. Pathological background data revealed a high frequency (61%) of hand, foot, and mouth disease among the onychomadesis cases. Coxsackievirus A10 was the most commonly detected enterovirus in both case and control groups (49%). Other enteroviruses such as coxsackieviruses A5, A6, A16, B1, and B3; echoviruses 3, 4, and 9; and enterovirus 71 were present in low frequencies in the case and control groups (3-9%). The 2008 onychomadesis outbreak in the metropolitan area of Valencia was associated with an outbreak of hand, foot, and mouth disease primarily caused by coxsackievirus A10.