Topical treatment with 13-cis-retinoic acid improves Darier's disease and induces the expression of a unique keratin pattern.

A patient with Darier's disease was treated topically with either 13-cis-retinoic acid 0.1%, all-trans-retinoic acid 0.05% or their cream base only. Both 13-cis-retinoic acid and all-trans-retinoic acid were effective. However, all-trans-retinoic acid had to be discontinued because of irritation. By contrast, 13-cis-retinoic acid was well tolerated and resulted in a complete remission. Both retinoids caused a marked change in the expression of cytokeratins. The most remarkable observation was the expression of cytokeratins 4, 13 and 19 at retinoid-treated areas. These cytokeratins are absent in adult normal or diseased epidermis and hence provide a cell-biological tool to substantiate a retinoid effect.     

Keratins 2 and 4/13 in reconstituted human skin are reciprocally regulated by retinoids binding to nuclear receptor RARα

Please cite this paper as: Keratins 2 and 4/13 in reconstituted human skin are reciprocally regulated by retinoids binding to nuclear receptor RARα. Experimental Dermatology 2010; 19: 674–681. Abstract: Disorders of keratinization are often treated with vitamin A derivatives (retinoids) which affect keratinocyte differentiation, including keratin (KRT) gene expression. In vivo, suprabasal keratinocytes normally express only keratin (K) 1, K2 and K10, but after topical application of all‐trans retinoic acid (ATRA), the granular cells will additionally express K4 and K13, i.e. keratins normally present in oral mucosa and in cultured epidermal keratinocytes. To learn more about the retinoid regulation of keratin expression under in vivo‐like conditions, we cultured keratinocytes on de‐epidermized dermis in only 0.5% serum. These cells produce a normal‐looking epidermis that expresses high mRNA levels of KRT1, KRT2 and KRT10, but minimal amounts of KRT4 and KRT13. Addition of ATRA to the medium for 48 h caused a dose‐dependent increase in KRT4/KRT13 and a down‐regulation of KRT2 mRNA. An increase in K4 protein was also found. The response was greater than the up‐regulation of another retinoid‐regulated gene, CRABPII. By studying 10 retinoids with different affinities for the retinoic acid receptors (RAR) and retinoid X receptors (RXR) isoforms, the reciprocal expression of KRT2 and KRT4/KRT13 could be connected with agonists for RARα. Two of these agonists, CD336/Am580 and CD2081, altered the expression profile with similar potency as the pan‐RAR agonists ATRA and CD367. Co‐addition of a pan‐RAR antagonist (CD3106/AGN193109) markedly inhibited the induction of KRT4/KRT13 expression, whereas the down‐regulation of KRT2 was less affected. In conclusion, RARα agonists elicit a reciprocal modulation of KRT2 and KRT4/KRT13 expression in human epidermis, but whether or not the keratin genes also possess RARα‐specific regulatory elements is still unclear.     

Effect of retinoids on hyperproliferation-associated keratins K6 and K16 in cultured human keratinocytes: a quantitative analysis.

The keratin patterns of human epidermal keratinocytes cultured on a 3T3-feeder layer in the presence of 10(-8) M non-aromatic (all-trans retinoic acid and 13-cis retinoic acid) and polyaromatic (arotinoid, arotinoid-sulfone, and free arotinoic-acid) retinoids were analyzed by high resolution one- and two-dimensional gel electrophoresis and immunoblotting. Laser densitometric evaluation of one-dimensional gels allowed to quantitate the changes within the keratin patterns and revealed an increase in the expression of keratins K13, K15, and K19 as induced by both non-aromatic and polyaromatic retinoids, except for the parent compound arotinoid. This would then indicate that such keratinocytes are pursuing a more embryonic type of differentiation. In evaluating the data for the hyperproliferation-associated keratins K6 and K16 we noticed an unexpected result: except for all-trans retinoic acid, these two keratins showed opposite responses. As compared to control cultures, the amount of K6 did generally increase, while K16 was reduced, with arotinoid acid being the most effective retinoid. The apparently uncoupled expression of K6 and K16 appeared also to be concentration dependent when 13-cis retinoic acid at concentrations of 10(-9), 10(-8), and 10(-7) M was analyzed. Considering the overall antiproliferative potency of retinoids, we therefore conclude that K16 alone, rather than the pair K6/K16, should be regarded as a proliferation-related keratin and as such may be used as a sensitive marker to evaluate keratinocyte proliferation.     

Cutaneous human papillomaviruses persist on healthy skin

Cutaneous human papillomaviruses (HPVs) are frequently found in healthy skin and have also been implicated in non-melanoma skin cancer. For genital HPV types, a persistent infection with one of the high-risk types is a prerequisite for the development of cervical cancer. However, there is only limited data on whether infections with cutaneous HPV types persist over time. Serial forehead swab samples collected from 63 volunteers (42 healthy individuals and 31 renal transplant recipients (RTRs)), sampled 6.3 years (range: 5.0-7.0 years) apart, were analyzed for HPV using general primer PCR, cloning, and sequencing. Among the healthy individuals, the prevalences of HPV were 69% (29/42) at enrolment and 71% (30/42) at follow-up. Among the individuals positive at baseline, 48% (14/29) had a persistent infection. Among the RTRs, 71% (15/21) were positive for HPV at enrolment and 90% (19/21) at follow-up. A persistent infection was detected in 33% (5/15). In total, HPV was detected in 44 of the samples collected at baseline and the same virus was found at follow-up in 43% (19/44). Persistence was not significantly associated with age, sex, immunosuppressive treatment, history of warts, or genus of HPV. We conclude that cutaneous HPV infections commonly persist over several years on healthy skin.     

Effects of 13-cis-retinoic acid, all-trans-retinoic acid, and acitretin on the proliferation, lipid synthesis and keratin expression of cultured human sebocytes in vitro.

The aim of this study was to determine the effects of 13-cis-RA, all-trans-RA, and acitretin on the proliferation, lipid synthesis, and keratin expression of human sebocytes in vitro and to elucidate possible mechanisms of retinoid action on sebaceous glands at the cellular level. It was found that 13-cis-RA and all-trans-RA decreased sebocyte proliferation in a dose- and time-dependent manner, with a 13-cis-RA-IC50 of 10(-5) M (after 7 d) and 10(-6) M (after 14 d) and an all-trans-RA-IC50 of 10(-7) M (after 14 d; no IC50 after 7 d). Acitretin inhibited sebocyte proliferation only at 10(-5) M. Furthermore, 13-cis-RA was the most potent inhibitor of acetate incorporation into lipids, which indicated lipid synthesis (48.2% reduction), followed by all-trans-RA (-38.6%), and by acitretin (-27.5%). All retinoids tested markedly decreased the synthesis of triglycerides, wax/stearyl esters, and free fatty acids in cultured sebocytes, whereas squalene synthesis remained uninfluenced and cholesterol synthesis slightly increased. On the other hand, keratin 5 was down-regulated, keratin 17 was up-regulated, and the expression of keratin 13 was virtually unaffected by all retinoids tested. Keratins 6 and 16 were down-regulated by 13-cis-RA and by all-trans-RA, keratin 14 was down-regulated by 13-cis-RA only, and keratin 19 was up-regulated by all-trans-RA. These investigations indicate that 13-cis-RA and, to a lesser extent, all-trans-RA are potent inhibitors of both cell proliferation and lipid synthesis in human sebocytes in vitro, whereas acitretin only decreases lipogenesis in this model. In addition, retinoids may modify the differentiation of sebocytes in vitro by modulating keratin expression. Models of cultured human sebocytes are useful tools for further investigations on the sebaceous gland and its activity at the cellular level.     

Treatment of cutaneous T-cell lymphoma with retinoids

Retinoids are biologic regulators of differentiation, proliferation, apoptosis, and immune response. Retinoids (all-trans retinoic acid, 13-cis-retinoic acid, and the synthetic analogs isotretinoin, etretinate, and acitretin) have been used for years as monotherapy and/or in combination for treatment of cutaneous T-cell lymphomas (CTCL). Orally administered bexarotene, the first synthetic highly selective retinoid X receptor retinoid to be approved by the Food and Drug Administration for CTCL, was shown to be active against the cutaneous manifestations of all stages of CTCL. The topical gel formulation was also effective for early cutaneous manifestations of CTCL or as an adjunct to systemic or phototherapy. Use of retinoids in future long-term clinical trials and their eventual application in CTCL regiments will require strategies to decrease the side effects of existing retinoids, identify novel receptor subtype-selective retinoids with better therapeutic index, and explore biologically based synergistic combination therapies with other active agents.     

Prevalence of benign cutaneous disease among Oxford renal transplant recipients

Background The burden of malignant and benign cutaneous disease among renal transplant recipients (RTR) is substantial. Little attention is given to non‐malignant skin problems in the literature despite their potential impact on quality of life or on aesthetics – which may contribute to poor compliance with immunosuppressive medications post‐transplantation. Objectives The aim of this study was to examine prevalence of benign cutaneous disease in a group of RTRs and identify risk factors for individual cutaneous conditions. Methods All cutaneous findings were recorded in a single full body skin examination of 308 RTRs. Data on medical, transplant and medication history were obtained from questionnaire and medical records. Odds ratios were calculated to look at associations between benign cutaneous diseases and various potential risk factors after controlling for gender, age, time since transplantation and skin type. Results Cutaneous infections such as viral warts (38%), fungal infection (18%) and folliculitis (27%) were common and usually chronic. A range of pilosebaceous unit disorders were observed with hypertrichosis being strongly associated with ciclosporin (P < 0.0001). Other iatrogenic cutaneous effects included gingival hyperplasia (27%) and purpura (41%). We identified seborrhoeic warts and skin tags in 55% and 33% respectively. Inflammatory dermatoses were rare (< 2%) apart from seborrhoeic dermatitis (9.5%). Discussion In this first comprehensive study on prevalence of benign cutaneous diseases in a UK transplant population, a wide range of skin disorders was identified. It is therefore important that RTRs have access to dermatology services post‐transplantation for appropriate management of benign cutaneous conditions as well as early detection of cutaneous malignancy and education regarding risks of sun exposure.     

Phenotypic/genotypic correlations in patients with epidermolytic hyperkeratosis and the effects of retinoid therapy on keratin expression

Dominant-negative mutations in the KRT1 and KRT10 genes cause epidermolytic hyperkeratosis, a rare form of ichthyosis sometimes associated with palmoplantar keratoderma. Although there is no permanent cure, some patients improve on retinoid therapy. More knowledge is needed, however, about the mechanism of action of retinoids and the genotypic/phenotypic correlations in this disease. Thirteen patients from 10 families with generalized disease and 2 sporadic patients with nevoid lesions were studied, probably representing most of the patients in Sweden and Norway. All patients, except one nevoid case, were known to have KRT1 or KRT10 mutations. Those with mutated keratin 1 (K1) invariably had associated keratoderma (n=6). In contrast, only 1 of 7 patients with K10 mutations had this problem (p = 0.0047). Five out of 6 patients with KRT10 mutations benefited from treatment with oral acitretin (5-25mg/day) or topical tretinoin/tazarotene, but none of the patients with KRT1 mutations derived any benefit. Quantitative analysis of K1 and K10 mRNA in skin biopsies obtained before and after retinoid therapy (n=8) showed no consistent down-regulation of mutated keratin that would explain the therapeutic outcome. Instead, the mRNA expression of K2e (a normal constituent of the upper epidermis) diminished especially in nonresponders. In contrast, K4 mRNA and protein (marker of retinoid bioactivity in normal epidermis) increased in almost all retinoid-treated patients. In conclusion, our study confirms a strong association between KRT1 mutations and palmoplantar keratoderma. Retinoid therapy is particularly effective in patients with KRT10 mutations possibly because they are less vulnerable to a down-regulation of K2e, potentially functioning as a substitute for the mutated protein in patients with KRT1 mutations.     

Pharmacokinetics of topically applied radiolabeled retinoids in hairless mouse epidermis and dermis after single applications

The retention of tritium-labeled all-trans-retinoic acid (RA), 13-cis-retinoic acid (13-cis-RA), aromatic retinoid, and arotinoid ethyl ester in the epidermis and dermis of hairless mice was measured up to 24 h following a single topical application in an acetone vehicle. The radioactivity in the tissues was extractable with chloroform:methanol, and the identities of the radioactive species extracted were confirmed as retinoids using thin-layer chromatography. All the retinoids were absorbed into the skin rapidly. After an initial period of distribution and penetration (lasting for about 1 h) the amount of the applied retinoid remaining in the epidermis and dermis decreased more slowly, obeying first order (exponential) decay kinetics. Both the arotinoid and the aromatic retinoid persisted for longer in the epidermis than equivalent doses of RA or 13-cis-RA. The half-lives of the retinoids in the dermis tended to be longer than in the epidermis, except for the arotinoid. Aromatic retinoid persisted for longest in the dermis with a half-life of 11 h.     

顽固性扁平疣患者接种新型冠状病毒灭活疫苗后皮损自行消退一例

患者,男,26岁。2年前无明显诱因面部、上肢出现多发扁平丘疹,曾多次就诊于我院,诊断为"扁平疣"给予维A酸类药物外用、CO₂点阵激光治疗,效果欠佳。2021年5月13日患者行COVID-19-1(Vero Cell)(新型冠状病毒灭活疫苗-北京生物?,批号2021020088)首剂接种,1天后扁平疣皮损变红,自觉瘙痒明显,于2021年5月17日来我院就诊,未予药物治疗,嘱观察,2021年5月23日复诊时疣体枯萎脱落。     

Oral retinoid use reduces cutaneous squamous cell carcinoma risk in patients with psoriasis treated with psoralen-UVA: a nested cohort study

BACKGROUND: Small open studies of patients at high risk for squamous cell carcinoma (SCC) of the skin suggest that oral retinoid use reduces the risk of these tumors. Among patients at lower risk, randomized trials of low doses of retinoids did not demonstrate significant chemopreventive effects. Patients with psoriasis treated with oral psoralen-UVA have a high risk of SCC development. Oral retinoids are used to treat psoriasis. We performed a nested cohort study to assess whether oral retinoids reduce skin cancer risk among patients with psoriasis exposed to psoralen-UVA. METHODS: From 1985 to 2000, 135 patients (11.3% of surviving patients in our cohort) used retinoids for at least 26 weeks in 1 year or more. For these 135 patients, we compared each person's SCC and basal cell carcinoma incidence during years of substantial oral retinoid use and other years. We used Poisson regression models to adjust for potential confounders. RESULTS: In a paired analysis, which compared each patient's own tumor experience while using and not using retinoids, retinoid use was associated with a 30% reduction in SCC incidence (196 SCCs/1000 and 302 SCCs/1000 years of use and no use, respectively; P =.002). After adjusting for other factors associated with SCC risk, the incidence of SCC was significantly decreased during years of substantial retinoid use (incidence rate ratio = 0.79; 95% confidence interval = 0.65, 0.95). Oral retinoid use and basal cell carcinoma incidence were not significantly associated. CONCLUSION: In patients with psoriasis treated with psoralen-UVA, systemic retinoid use reduced SCC risk but did not significantly alter basal cell carcinoma incidence.     

The rationale for using a topical retinoid for inflammatory acne

Both comedogenesis and the development of inflammatory lesions in acne vulgaris appear to be related to genetic as well as immune processes. The key regulatory cytokine, interleukin-1alpha, has recently been documented as playing a major role in both the hypercornification and the orchestration of immune factors, ultimately resulting in noninflammatory and inflammatory lesions. Topical retinoids, such as tretinoin, and topical retinoid analogs, such as adapalene and tazarotene, help normalize the abnormal follicular keratinocyte desquamation - a key pathophysiologic factor in comedogenesis. This normalization also helps mitigate against the development of a propitious microenvironment for Propionibacterium acnes. Preclinical data suggest that topical retinoids and retinoid analogs may also have direct anti-inflammatory effects. A wealth of clinical data confirms that topical retinoids and retinoid analogs significantly reduce inflammatory lesions. Comparative clinical trials also demonstrate that adapalene has the best cutaneous tolerability profile of all these agents. Optimal therapy for inflammatory acne would involve the use of topical retinoids or retinoid analogs combined with oral or topical antibacterials.     

RARα/RXR synergism potentiates retinoid responsiveness in cutaneous T‐cell lymphoma cell lines

Retinoids, natural and synthetic derivatives of vitamin A, induce cellular changes by activating nuclear retinoic acid receptors (RAR) and retinoid X receptors (RXR). Although the ability of retinoids to govern gene expression is exploited clinically for cancer therapeutics, the full benefit of retinoid‐based strategies is unrealized due to detrimental side effects. Delineating the receptors that prompt cellular outcomes is critical to advancing retinoid‐based approaches. Here, we identify the receptors that evoke multiple responses in cutaneous T‐cell lymphoma (CTCL). The data demonstrate that RARα drives integrin β7‐dependent adhesion and CCR9‐mediated chemotaxis in CTCL cells. Of note, concomitant activation of RARα and RXR nuclear receptors yielded synergistic increases in adhesion and migration at concentrations where single agents were ineffective. As the established paradigm of retinoid action in CTCL is apoptosis and growth arrest, the role of RARα/RXR in these events was studied. As with adhesion and migration, RARα/RXR synergism prompted apoptosis and dampened CTCL cell proliferation. Strikingly, RARα/RXR synergism induced responses from CTCL cell lines previously reported to be unresponsive to retinoids. These data provide a novel framework that may further refine a proven CTCL therapy.     

Common Association of HPV 2 with Anogenital Warts in Prepubertal Children

Abstract: Anogenital (AG) warts in 31 prepubertal children were HPV typed by nonisotopic in situ hybridization (NISH) using digoxigenin labeled probes for human papilloma virus (HPV) types 1–5, 6,11,16,18, 31, and 33. Mode of transmission was determined from historical, clinical, and laboratory data independent of HPV typing. HPV 2 was detected most commonly (13/31 warts) followed by HPV 6 (7/31), HPV 11 (5/31), and HPV 16 (1/31). Although not reaching statistical significance, our results suggested that a mucosal HPV type (6,11,16) in a child's AG warts implied transmission from mucosal warts and conversely cutaneous HPV 2 transmission from warts at a cutaneous site. HPV typing provided no helpful information regarding actual mode of transmission of AG warts In these children. The high prevalence of HPV 2 in children's AG warts and the low prevalence of sexual abuse (2 of 31 children) found in this study suggest innocent auto- or heteroinoculation from cutaneous warts may be a common means by which children acquire AG warts.     

Topical Retinoids in Acne Vulgaris: A Systematic Review

Background

Topical retinoids are a first-line treatment for acne vulgaris.

Objective

This systematic review aims to evaluate the efficacy, safety, and tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris.

Methods

A PubMed and Embase search was conducted using the search terms ‘adapalene,’ ‘tretinoin,’ ‘tazarotene,’ and ‘acne vulgaris.’ Selection of articles fit the following inclusion criteria: clinical trials evaluating both efficacy and safety/tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris and published between January 1, 2008 and September 1, 2018. Exclusion criteria included clinical trials involving 20 subjects or fewer, subjects under 12 years of age, and topical retinoid combination therapies with moisturizers or aloe vera. Of 424 search results found, a total of 54 clinical trials were chosen based on selection criteria.

Results

Topical retinoids are superior to vehicle in improving Investigator Global Assessment and Investigator’s Static Global Assessment (24.1–28.8% and 13.3–17.3%, respectively; p < 0.001). A topical retinoid combined with benzoyl peroxide led to IGA improvement compared with vehicle (26.1–34.9% vs 7–11.8%; p < 0.001) at Week 12. Topical retinoid plus an oral antibiotic was superior to vehicle in reducing lesion counts (64–78.9% vs 41–56.8%, p < 0.001). There was no significant difference in efficacy between tretinoin and tazarotene. Tretinoin 0.05% resulted in 62% of patients experiencing AEs compared with adapalene 0.1% (19%) and adapalene 0.3% (40%). More patients receiving adapalene were tolerant of the AEs compared with tazarotene (55.4% vs 24.4%; p < 0.0012).

Conclusions

Topical retinoids are safe and efficacious for the treatment of acne vulgaris. They should be used in combination with benzoyl peroxide to optimize results in patients. The differences in efficacy of topical retinoids appears minor; therefore, the type of topical retinoid is not as important as choosing a particular strength of topical retinoid and combining it with an antimicrobial agent. Adapalene has a superior tolerability profile amongst topical retinoids.

     

Prevalence of cutaneous bacterial infections and nasal carriage of Staphylococcus aureus in recipients of renal transplants

Background.  Renal transplant recipients (RTRs) often develop bacterial infections as a result of their long-term immunosuppressive treatment. However, there is no published case–control study of cutaneous bacterial infections in this population, and the prevalence of nasal Staphyloccus aureus carriage and its role in cutaneous bacterial infections in RTRs are not known.
Aims.  To determine whether the prevalence of cutaneous bacterial infections and nasal S. aureus carriage are increased in RTRs and to investigate the association between nasal S. aureus carriage and cutaneous staphylococcal infections.
Methods.  In total, 66 outpatient RTRs and 67 controls were investigated for the presence of cutaneous bacterial infections. Bacterial cultures were taken from clinically suspicious cutaneous lesions, and three nasal swabs were collected to detect nasal S. aureus colonization.
Results.  Cutaneous bacterial infection was suspected in 42.4% of RTRs, and in 14.2% of controls. However, of the lesions that could be cultured, microbiologically proven cutaneous bacterial [methicillin-sensitive S. aureus (MSSA)] infections were confirmed in only two RTRs and one control subject. Nasal S. aureus carriage was found in 10.6% of RTRs and 29.9% of controls ( P  < 0.05). Both RTRs with MSSA infection were nasal carriers, whereas nasal S. aureus carriage was not detected in the only control subject with MSSA infection. All S. aureus isolates were oxacillin-sensitive.
Conclusion.  Screening for nasal S. aureus carriage does not seem to assist in preventing staphylococcal bacterial infections in outpatient RTRs.     

Acute or chronic topical retinoic acid treatment of human skin in vivo alters the expression of epidermal transglutaminase, loricrin, involucrin, filaggrin, and keratins 6 and 13 but not keratins 1, 10, and 14.

Histologic and immunocytochemical analyses were performed on cutaneous biopsies from 10 patients treated with retinoic acid under occlusion for 4 d compared to biopsies from 19 patients treated nightly for 16 weeks. Acute application of RA caused epidermal thickening (9 of 10 samples), stratum granulosum thickening (7 of 10), parakeratosis (4 of 10), a marked increase in the number of cell layers expressing epidermal transglutaminase (7 of 10), and focal expression of two non-epidermal keratins, K6 (8 of 10) and K13 (2 of 10), changes also observed with chronic treatment. Involucrin, filaggrin, and loricrin were also altered in samples from both acute and chronic treatment. An increased number of cell layers expressed both involucrin and filaggrin from both the acute (7 of 10) and chronic (14 of 19) treatment groups. In the acute group, loricrin expression was significantly reduced or absent in some regions of the epidermis (5 of 10), whereas most chronic samples showed an increased number of cell layers expressing loricrin (12 of 19). The pattern of expression of three major epidermal differentiation products, keratins K1, K10, and K14, was not significantly altered in any of the acute or chronic samples, although there was a slight reduction in the detection of K10 in two of the acute samples. Thus, acute topical RA treatment under occlusion caused substantial changes in the epidermis, and reproduced most, but not all of the effects of chronic treatment.     

Retinoids inhibit the differentiation of embryonic-mouse mesenchymal cells in vitro

Summary The influence of all-trans retinoic acid, 13-cis retinoid acic and two aromatic retinoids (Ro 10-1670, Ro 11-1430) on the chondrogenic differentiation of mesenchymal cells in vitro was studied electronmicroscopically. Organ cultures of limb buds from mouse embryos (Day 11) and high-density cultures of embryonic-mouse mesenchymal cells (Day 12) were used as experimental models. After a 6-day culture in the control medium, the development of hyaline cartilage was observed in both systems. In cultures which were treated with retinoids from Day 1 through Day 3 and then incubated in the control medium for 3 more days, the mesenchymal cells still maintained the morphological features of the blastema stage; cartilage synthesis was reduced (low retinoid concentrations) or completely absent (high retinoid concentrations). These findings indicate that the treatment of embryonic-mouse mesenchymal cells with retinoids induces a persistent and dose-dependent inhibition of chondrogenic differentiation, which in quantitative terms, is variably expressed during treatment with different retinoids. These inhibitory effects of retinoids on chondrogenesis are probably implicated in the pathogenetic mechanisms of their teratogenic action in vivo.     

High viral load of human wart-associated papillomaviruses (PV) but not β-PV in cutaneous warts independent of immunosuppression

Background  A broad spectrum of human papillomaviruses (HPV) has been detected in warts from immunocompetent patients and a much more diverse range from immunosuppressed organ transplant recipients (OTR).
Objectives  To determine the HPV types in warts from OTR, we assessed present infections of mucosal (α-PV), wart-associated (α-, μ- and ν-PV) and cutaneous HPV types (β-/γ-PV) in immunocompetent patients and OTR.
Patients/methods  Forty-one warts from 29 immunocompetent patients (non-OTR) and 53 warts from 33 OTR were analysed for DNA of human α-, β-, γ-, μ- and ν-PV. For frequent types viral load was determined by quantitative real-time PCR.
Results  Compared with non-OTR prevalence of cutaneous HPV (79% vs. 49%, P  <   0·01) and the number of multiple infections (62% vs. 17%, P  <   0·0001) were significantly increased. The mean viral load of the wart-associated HPV was more than 10⁵-fold higher compared with human β-PV in both cohorts.
Conclusions  The high load of wart-associated HPV suggests an active role of these viruses rather than cutaneous types in warts independent of immunosuppression; however, the substantial fraction of warts with low HPV genome copies remains to be explained.