Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application

Background/aim  Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs.
Methods  Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2–5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N₂ cryosurgery (spray, two cycles, 10–20 s) and imiquimod was continued for additional 2–12 weeks (median, 4). The outcome after at least 18 months of follow-up (18–24 months) is currently reported.
Results  Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%).
Conclusions  'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results.     

Cryosurgery during topical imiquimod: a successful combination modality for lentigo maligna

Background Either cryosurgery or topical imiquimod have been used to treat patients with lentigo maligna in cases where surgery is not feasible. Methods We report a patient with lentigo maligna, who was treated with the combination of topical imiquimod and cryosurgery, and review the rationale, which led us to design the present combined cryo‐immunological treatment modality. Results Sustained clearance of lentigo maligna to date (26 months after treatment). The successful treatment of this patient was based on the following rationale: A cryosurgery session during continuing imiquimod application may: (i) reinforce apoptosis of tumor cells; (ii) strengthen antiangiogenesis in the treated tumor; and (iii) build‐up a potent tumor‐destructive immune response by a cascade of events starting with imiquimod‐promoted attraction of immature dendritic antigen‐presenting cells (DCs) into the tumor. DCs further mature within the tumor‐antigen‐rich environment of subsequently cryo‐destructed tumor and upon imiquimod‐driven migration into the peripheral lymph nodes can stimulate a specific antineoplastic cell‐mediated immunity. Finally, continuing imiquimod application after cryosurgery may increase recruitment of activated effector cells into the tumor tissue leading to its destruction. Conclusion Cryosurgery during continued topical imiquimod seems to be a promising treatment for lentigo maligna.     

Immunocryosurgery as monotherapy for lentigo maligna or combined with surgical excision for lentigo maligna melanoma

The incidence of lentigo maligna (LM), in situ (LM) or invasive (lentigo maligna melanoma, LMM), has increased during the last decades. Due to functional or cosmetic outcomes, optimal treatment with surgical excision may not be appropriate in some cases. We tried less invasive therapy, immunocryosurgery, as a single treatment for LM or combined with surgery for LMM, with better aesthetic results. Three patients with LM or LMM not amenable to complete surgical excision were selected. LMM patients underwent limited surgical resection of the invasive area. Subsequently, a combined treatment with topical imiquimod and cryosurgery was performed. The LM patient received immunocryosurgery directly. All of them were free of local and systemic disease at 48, 42 and 41 months after discontinuation of therapy. We consider that immunocryosurgery is an alternative option for LM or even for LMM (after removal of the invasive tissue with narrow margins) in poor surgical candidates, with good therapeutic, functional and cosmetic results.     

Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub‐clinical and clinical actinic keratosis during imiquimod treatment

Please cite this paper as: Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub‐clinical and clinical actinic keratosis during imiquimod treatment. Experimental Dermatology 2010; 19: 641–647. Background: During treatment of actinic keratosis (AK) lesions with imiquimod sub‐clinical lesions often become visible. It is, however, unclear whether these sub‐clinical lesions would be detectable beforehand. Objective: The aim of this pilot study was to compare two techniques, cross polarized light photography (CPL) and fluorescence diagnosis (FD) using methyllevulinic acid and illumination with Wood’s lamp for their ability to detect sub‐clinical lesions. These findings were also compared with biopsy results taken before and after treatment with imiquimod 5% cream or vehicle. Methodology: Twelve patients with at least five clinically visible AK lesions in a single contiguous 20 cm² area on the head were recruited. Patient eligibility was determined at the screening visit, when they were randomized to treatment. The randomization was 3:1, active to vehicle (nine treated with imiquimod, three with vehicle cream) for a total duration of 24 weeks (six clinic visits). Patients were assessed for baseline AK lesion counts (clinical and sub‐clinical) at the screening visit and final counts at week 20. Results: The number of clinically observed AK lesions was significantly lower at week 12 and week 20 compared with baseline following imiquimod treatment versus vehicle. The number of counted lesions were significantly higher using the CPL method compared with clinical counting with imiquimod treatment at baseline (8.3 ± 3.4 vs 5.8 ± 1.3; P = 0.027) and week 20 (4.8 ± 2.4 vs 3.0 ± 1.7; P = 0.02) but not in the vehicle group. The FD lesion counting method did not show a significant increase in the number of detected lesions compared with clinical analysis in the imiquimod and placebo groups but when comparisons were performed using pooled data (treatments and visits combined) the results were significant. Conclusion: The number of sub‐clinical and clinical AK lesions detected during treatment with imiquimod can be better demonstrated using the methods of CPL and FD, but statistical significance was reached only using the CPL method. This is only a preliminary study with a small number of patients and as a result it is difficult to conclude both statistical and clinical significance. However, results were encouraging and indicate that larger studies are needed to demonstrate the relevance of these two new methods for improved detection of clinical and especially sub‐clinical AK lesions.     

Die solare Keratose: Von der Präkanzerose zum präinvasiven Plattenepithelkarzinom – Therapeutischer Ansatz nach dem Bioinduktionsverfahren

Background: Solar keratoses are precancerous lesions in chronically UV‐damaged skin with histological features consistent with pre‐invasive squamous cell carcinoma. They require therapeutic intervention in order to prevent progression towards invasive carcinoma. Treatment options include topical medications and destructive methods. We report on a new approach – topical bioinductive therapy with imiquimod 5 % cream. Patients and methods: In a prospective case series, 7 patients with solar keratoses have been treated with topical imiquimod 5 %. The cream was applied 5 days/week over 2 weeks. After end of treatment, the outcome was assessed at regular control visits and, in some cases, histologically confirmed. One patient was followed up as untreated control. Results: In 6 of the 7 treated patients, the lesions cleared completely; one patient did not respond. The patients did not show new solar keratoses during a follow‐up period of about 2 years. The untreated patient showed spontaneous clearance of his keratoses. Local skin reactions during treatment included erythema, oedema and erosions in varying degrees, all of which completely resolved. Conclusions: Bioinductive therapy with imiquimod 5 % cream represents a promising therapeutic approach for cutaneous precancerous lesions such as solar keratoses.     

Increased number of mast cells in the dermis in actinic keratosis lesions effectively treated with imiquimod

Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll‐like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non‐melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions. With the dermatoscope, though the mean erythema score was not significantly different between the cured lesions and the unresponsive lesions, the erythema/red pseudo‐network (“strawberry”) pattern was decreased significantly in the cured lesions. By immunohistochemistry, the number of Ki‐67‐positive proliferative cells in the epidermis was decreased and that of CD117‐positive mast cells in the dermis was increased in the responding lesions. To the best of our knowledge, this is the first study demonstrating that the number of mast cells in the dermis was increased in AK lesions effectively treated with imiquimod. Our present result suggests that mast cells may contribute an antitumor effect in human skin treated with topical imiquimod.     

Seborrheic keratoses: a study comparing the standard cryosurgery with topical calcipotriene, topical tazarotene, and topical imiquimod

BACKGROUND: Patients with seborrheic keratoses frequently desire an effective topical therapy for seborrheic keratoses. OBJECTIVE: To compare topical calcipotriene, topical tazarotene, and topical imiquimod with standard cryosurgery in the treatment of seborrheic keratoses. METHODS: Fifteen patients with numerous seborrheic keratoses were enrolled in an open-label study comparing cryosurgery with topical agents. Eight separate seborrheic keratoses were selected to be treated with topical medications. One lesion was treated with cryosurgery. RESULTS: One treatment with cryosurgery led to clinical and histological improvement of all lesions treated. Neither scarring nor recurrence resulted in cryosurgery. In seven of 15 patients, tazarotene 0.1% cream applied BID caused clinical improvement in lesions within 16 weeks. CONCLUSION: Cryosurgery produces clinical and histological improvement of seborrheic keratoses. The result with cryosurgery was cosmetically acceptable to all patients. Responders to tazarotene cream 0.1% found it cosmetically acceptable.     

Serum substance P and calcitonin gene-related peptide levels in Behçet's disease and their association with disease activity

Background. Substance P (SP) and calcitonin gene‐related peptide (CGRP) are neuropeptides that have a role in several cutaneous diseases and inflammations. Aim. To evaluate SP, CGRP and serum interleukin (IL)‐8 levels in Behçet's disease (BD) and to explore the relationship of these peptides with BD activity. Methods. The study group comprised 30 patients with BD, and 30 healthy individuals acted as controls. Serum levels of SP, CGRP and IL‐8 were determined by micro‐ELISA test during the active and inactive disease periods of patients with BD. These data were compared with each other and controls. Active and inactive periods of BD were established. Results. The mean ± SD serum CGRP (ng/ml) and IL‐8 levels (pg/ml) in inactive BD (5.87 ± 2.49 and 0.62 ± 0.24, respectively) were significantly higher than the control group (4.74 ± 1.17 and 0.46 ± 0.11) (P < 0.05 for both). The difference between serum CGRP and IL‐8 levels in active BD were also significantly higher than in inactive BD (P < 0.05 for both). Serum SP values (ng/ml) in active BD (18.27 ± 5.38) were significantly higher than in inactive BD (15.26 ± 5.74) and controls (12.6 ± 4.45) (P < 0.05 for all), whereas the difference between the serum SP values in inactive BD and the control group was not statistically significant (P > 0.05). Conclusion. Serum SP and CGRP may have a role in the pathogenesis of BD. In addition, serum IL‐8, SP and CGRP levels can be used as laboratory parameters indicating activity in BD.     

Long‐term follow‐up of photodynamic therapy with a self‐adhesive 5‐aminolaevulinic acid patch: 12 months data

Background Photodynamic therapy with a self‐adhesive 5‐aminolaevulinic acid (5‐ALA) patch shows high efficacy rates in the treatment of mild to moderate actinic keratosis (AK) in short term trials. Objectives The purpose of the trial was to follow up patients after successful 5‐ALA patch‐PDT at 3 month intervals over a total period of 12 months. Patients who had received placebo‐PDT or cryosurgery served for comparison. Patients/methods Three months after therapy, 360 patients from two separate randomized parallel group phase III studies (one superiority trial vs. placebo‐PDT, one noninferiority trial vs. cryosurgery) were suitable for the follow‐up study. Patients had to show at least one successfully treated AK lesion after initial therapy. A total of 316 patients completed the follow‐up. Results Twelve months after a single treatment, 5‐ALA patch‐PDT still proved superior to placebo‐PDT and cryosurgery (P < 0·001 for all tests). On a lesion basis, efficacy rates were 63% and 79% for PDT, 63% for cryosurgery and 9% and 25% for placebo‐PDT. Recurrence rates of patch‐PDT proved superior to those of cryosurgery (per protocol set: P = 0·011, full analysis set: P = 0·049). While 31% of cryosurgery lesions were still hypopigmented after 1 year, the 5‐ALA patch‐PDT groups showed hypopigmentation in 0% (superiority trial) and 3% (noninferiority trial) of the treated lesions. Conclusion Twelve months after a single 5‐ALA patch‐PDT the majority of lesions were still cleared with an excellent cosmetic outcome. 5‐ALA patch‐PDT proved to be superior to cryosurgery in the noninferiority study setting.     

Pain evaluation and control during and following the treatment of hypertrophic scars and keloids by contact and intralesional cryosurgery – a preliminary study

Background Intralesional cryosurgery effectively treats hypertrophic scars and keloids (HSK), but pain experienced by the patient during treatment can limit the application of cryosurgery. Objectives  To characterize the pain response during cryosurgical treatment of HSK, and to evaluate the pain experienced during contact and intralesional cryosurgery that employs a pain‐control protocol. Methods  Twenty‐nine patients (17 women, 12 men) aged 17 years and older (mean ages 31.9 ± 12.5 and 38.9 ± 18.6 years, respectively, P = 0.24), who were treated for a total of 36 HSKs by intralesional (n = 20; 22 cryotreatments) or contact (n = 9; 14 cryotreatments) cryosurgery were evaluated. The pain‐control protocol involved oral pain‐relief tablets (Dipyrone) and translesional local anaesthesia with Bupivacaine hydrochloride 0.5%. Pain evaluation according to the Visual Analogue Scale (VAS) (0–10 cm) was compared between the two groups at three time points: during cryosurgery, immediately after it, and 4 h later. Scores ≤3 cm were considered to define the ‘zone of analgesic success’. These results were compared with control data (contact cryosurgery without a pain‐control protocol; n = 56). Results  Pain in the intralesional group was significantly lower than that in the contact group during and immediately after cryotreatment. During: mean VAS = 1.68 ± 2.21 vs. 5.07 ± 4.01 cm; median VAS = 0.5 vs. 5.5 cm, respectively; P < 0.0001. Immediately after: mean VAS = 1.22 ± 1.77 vs. 5.38 ± 3.81 cm; median VAS = 0 vs. 6.0 cm, respectively; P = 0.001. The control group had more pain during treatment (mean VAS = 5.34 ± 2.31, median = 6.0) and 4 h later (mean = 3.79 ± 2.35, median = 4.0) than the intralesional group (P < 0.0001 and P = 0.988, respectively). The pain level in the control group during the cryotreatment did not differ from that in the contact group (P = 0.988). In the intralesional, contact and control groups analgesic success (VAS ≤3 cm) was achieved in 77.3%, 35.7% and 33.9%, respectively, of cases (P = 0.002) during cryotreatment, and in 54.5%, 42.9% and 33.9%, respectively, of cases 4 h after treatment (P = 0.24). Conclusions  The pain‐control protocol significantly reduced pain severity to tolerable levels (VAS ≤3 cm) during and following intralesional and contact cryosurgery. Intralesional cryosurgery caused the least pain during and immediately after treatment.     

Analysis of interleukin-10 levels in lesions of vitiligo following treatment with topical tacrolimus

Background Vitiligo is an acquired dermatological condition that is characterized by depigmentation of patches of skin. It is relatively common, occuring in about 0·38–0·50% of the general population, and can engender significant cosmetic disfigurement and psychological sequelae in the affected individual. Recent studies demonstrate that topical tacrolimus (Protopic^®; Astellas, Markham, ON, Canada) is efficacious in the treatment of vitiligo. We propose that the successful treatment of vitiligo with topical tacrolimus involves the unique immunosuppressive actions of the T lymphocyte T‐helper (Th) 2 cytokine, interleukin (IL)‐10. Objectives We aimed to monitor clinical changes in lesions of vitiligo treated with topical tacrolimus 0·1% ointment and quantify IL‐10 cytokine levels in nonvitiliginous skin, as well as lesions of vitiligo before and following topical tacrolimus therapy. Methods Clinical evaluation of lesions of vitiligo on the basis of surface area and follicular repigmentation under Wood’s lamp was performed in 20 enrolled adult patients. Biopsy specimens were obtained from nonvitiliginous skin, as well as lesions of vitiligo before and following topical tacrolimus therapy. Specimens were processed and analysed for expression of IL‐10 using the method of enzyme‐linked immunosorbent assay. Results A statistically significant mean ± SEM decrease in vitiligo lesion size of 41·0 ± 5·2% was observed following 3 months of treatment. A pattern of follicular repigmentation was noted by the third month of treatment for all patients completing the study. In addition, there was a statistically significant difference between IL‐10 expression in vitiligo lesions following treatment for 3 months with topical tacrolimus compared with untreated vitiligo lesions (P = 0·017) and normal skin (P = 0·004). Conclusions These results confirm that topical tacrolimus is an effective treatment for vitiligo. We propose that topical tacrolimus increases IL‐10 expression in vitiligo lesions, and thereby inhibits melanocyte destruction triggered by unchecked Th1 pathways in vitiligo.     

TNF-alpha gene 1031 T/C polymorphism in Turkish patients with Behçet's disease

Background Genetic factors that predispose individuals to Behçet's disease (BD) are considered to play an important role in development of the disease. The tumour necrosis factor (TNF)‐α gene, which is closely linked to the HLA‐B51 gene, is involved in susceptibility for BD. Recently, a polymorphism at position ?1031 within the TNF‐α promoter region was demonstrated to be responsible for susceptibility to BD in a British population. However, the functional effects of this polymorphism have not yet been determined. Objectives To investigate the possible relation of the TNF‐α–1031 T/C polymorphism with susceptibility to BD in a Turkish population and to determine the functional importance of this polymorphism. Methods Ninety‐nine unrelated patients (47 women, 52 men; mean ± SD age, 34·10 ± 10·53 years) with BD and 103 ethnically matched healthy controls (52 males, 51 females; mean ± SD age, 40·25 ± 14·15) were enrolled in the study. For genotyping, polymerase chain reaction – restriction fragment length polymorphism (PCR‐RFLP) analysis was employed. The functional importance of TNF‐α–1031 T/C polymorphism was determined with an enzyme‐linked immunospot (ELISPOT) assay. For this purpose, mononuclear cells obtained from BD patients and controls were analysed for TNF‐α and interferon (IFN)‐γ production. Results A significant difference was observed between BD patients and controls with respect to the allele frequency of TNF‐α–1031C [P = 0·018, OR = 1·83, 95% confidence interval (CI) = 1·07–3·13]. When the allele frequencies were analysed according to the clinical features, the T allele in patients with positive skin pathergy test (SPT) was significantly increased when compared with those of patients without these findings (P = 0·004, OR = 2·75, 95% CI = 1·3–5·86). To demonstrate the frequency of TNF‐α and IFN‐γ producing cells, mononuclear cells from four representative individuals of each genotype were used and the spontaneous and stimulated TNF‐α and IFN‐γ values (spot numbers) were analysed. Compared with the control groups, a significant increase was observed in the number of cells producing TNF‐α obtained from BD patients (P < 0·001). Moreover, the stimulation index for TNF‐α [bacterial lipopolysaccharide (LPS) stimulated/unstimulated] was higher for the CC genotype (9 ± 9·5) with respect to the other genotypes (TT; 1·3 ± 0·3 and TC; 1·2 ± 0·2). While the difference in the spontaneous IFN‐γ values between groups were not statistically significant, the stimulated IFN‐γ values were found to be significantly increased in the BD group when compared with the healthy control group (P = 0·004). Conclusions Our results showed that, in the Turkish population the TNF‐α–1031C allele is associated with susceptibility to BD. On the other hand, carrying the T allele may render patients more prone to developing a positive skin pathergy test. In addition, ELISPOT assays revealed that BD patients exhibited a significantly higher number of mononuclear cells producing TNF‐α, and cells obtained from patients with a CC genotype had a stronger response to LPS stimulation. The strong IFN‐γ response upon LPS stimulation in BD patients supports the previous findings that BD is a Th1 driven disease. These findings suggest that the TNF‐α–1031 polymorphism may have a functional effect and could explain the reason for high levels of TNF‐α production observed in BD patients.     

Cryosurgery is more effective in the treatment of primary, non-superficial basal cell carcinomas when applied during and not prior to a five week imiquimod course: a randomized, prospective, open-label study

Combinational cryosurgery during daily imiquimod application ('immunocryosurgery') efficiently cures invading basal cell carcinoma (BCC). Since timing of the cryosurgery is considered crucial for effectiveness, our aim was to compare efficacy of two different timing schemes of the combination of cryosurgery and topical imiquimod: Cryosurgery (a) 2 weeks after (Arm I) vs (b) prior to the initiation of a 5 week daily imiquimod course (Arm II). 16 patients with 21 BCC were recruited in this prospective, randomized, open-label trial. 14 patients with 17 BCC were evaluated (Arm I: 7 patients/10 tumors vs Arm II: 7 patients/7 tumors) during scheduled interim analysis at 6 month follow-up (two patients dropped out, one non-compliant and one lost to follow up). The trial was revoked because study Arm I ('immunocryosurgery') was significantly superior to Arm II (adjuvant imiquimod) in achieving tumor clearance (10/10 vs 3/7 tumors; p=0.0147) and by overall treatment efficacy (9/10 vs 2/7 relapse-free tumors; p=0.0345). The same overall efficacy persisted after at least 18 months follow-up for those patients with tumor clearance after the trial treatment. The timing of cryosurgery during imiquimod application substantially determines the efficacy of this combinational approach in the treatment of BCC.     

Kontrollierte schichtweise Abtragung anogenitaler Warzen mittels Argon‐Plasma‐Koagulation

Background: According to guidelines of the German STD Association, appropriate treatment of extensive anogenital warts with comparable recurrence rates includes cryotherapy, surgical excision, electrosurgery, CO₂‐ and Nd:YAG‐laser vaporisation. All these procedures are associated with varying degrees of risk for bleeding, release of potentially infectious aerosol, deep thermal destruction, slow wound healing, and scarring. Methods: Using argon‐plasma coagulation anogenital warts can be removed in layers in a controlled manner. High frequency current flows through the argon plasma to the tissue, allowing well‐controlled, superficial tissue destruction. Results: From January 2001 to March 2003, 54 patients with extensive genital, anal or anogenital warts were treated. After one treatment, 66 % of the patients remained disease‐free in the following 4 months. Thirteen patients (24 %) showed early recurrence after 4 weeks, five patients (9 %) at a later date. In these patients, further treatment, in 9 cases combined with topical imiquimod cream, were necessary for complete remission. Conclusion: Compared to other therapeutic procedures, argon‐plasma coagulation is a better controlled, quick and low‐risk option for the treatment of anogenital warts. Depending on the type of involvement and individual risk factors, postoperative treatment with topical imiquimod cream may be useful.     

Increased arterial stiffness assessed by pulse wave velocity in Behçet’s disease and its association with the lipid profile

Objective To evaluate the structural and functional properties of vessels in Behçet’s Disease (BD) using carotid‐femoral pulse wave velocity (PWV) and an echo‐tracking system. Methods BD patients without traditional cardiovascular risk factors were selected. All BD patients performed PWV and carotid ultrasound. BD patients were divided into groups based on the presence of systemic (vascular and/or ocular and/or central nervous system involvement) and vascular involvement. Healthy controls age‐ and sex‐matched with the same exclusion criteria were selected. Results A total of 23 BD patients (mean age 35.0 ± 7.6 years) had significantly higher PWV levels compared with controls (8.48 ± 1.14 vs. 7.53 ± 1.40 m/s, P = 0.017). Intima‐media thickness (594.87 ± 138.61 vs. 561.08 ± 134.26 μm, P = 0.371), diastolic diameter (6383.78 ± 960.49 vs. 6447.65 ± 1159.73 μm, P = 0.840), distension (401.95 ± 117.72 vs. 337.91 ± 175.36 μm, P = 0.225) and relative distension (6.26 ± 2.83 vs. 5.42 ± 2.46 μm, P = 0.293) were similar in both groups. The systemic disease group had significantly higher levels of PWV (8.79 ± 1.21 vs. 7.88 ± 0.72 m/s, P = 0.036) compared to those with exclusive mucocutaneous manifestations. BD patients with vascular involvement had similar PWV and echo‐tracking parameters compared to those without vascular involvement (P > 0.05), but had higher total and LDL cholesterol levels (P = 0.019 and P = 0.012, respectively). The multivariate linear regression analysis identified triglycerides as the most important factor in increasing PWV levels (P = 0.001) in BD. Conclusions PWV is more useful than carotid ultrasound in detecting structural and functional vascular damage in BD and emphasizes the role of the disease itself in promoting these alterations. Our findings also reinforce the need for rigorous control of all risk factors in BD, particularly lipoproteins.     

Serum levels of GRO-α are elevated in association with disease activity in patients with Behçet's disease

Background Although the etiology of Behçet’s disease (BD) is still unknown, neutrophils are implicated in its pathogenesis. Growth‐related oncogene‐α (GRO‐α) is a potent chemoattractant and activator for neutrophils. Objective To determine the role of GRO‐α in the pathogenesis of BD, we investigated serum GRO‐α levels in patients with BD. Materials and methods Sera from patients with BD (n = 57) and control subjects (n = 26) were measured by enzyme‐linked immunosorbent assay. Serum levels of GRO‐α were compared with clinical symptoms. Results Patients with BD had significantly elevated serum GRO‐α levels compared with healthy controls (121.7 ± 79.2 pg/ml vs. 75.9 ± 20.6 pg/ml, P < 0.01). Concerning the subgroups of BD, serum GRO‐α levels in active patients with BD (n = 35) were significantly higher than in inactive patients with BD (n = 22; 139.0 ± 92.8 pg/ml vs. 94.3 ± 36.2 pg/ml, P < 0.05). Also, as seen in previous studies, serum interleukin‐8 levels in patients with BD (52.4 ± 81.8 pg/ml) were significantly higher than in controls (13.9 ± 19.7 pg/ml, P < 0.01). Enhanced GRO‐α levels correlated with clinical symptoms such as erythema nodosum. Conclusion Our results indicate that serum levels of GRO‐α are elevated in patients with active stage BD, suggesting that GRO‐α may serve as a reliable marker for disease activity of BD.     

Er:YAG laser followed by topical podophyllotoxin for hard‐to‐treat palmoplantar warts

BACKGROUND AND OBJECTIVES: Palmoplantar warts are often hard to treat. They tend to relapse and the course of therapy is frustrating in many cases. The erbium:YAG laser (Er:YAG) with a wavelength of 2.94?μm is capable of achieving a rapid and precise ablation of warts, but about 14% of patients are non‐responders as shown in a previous study. Podophyllotoxin is an established antimitotic agent derived from podophyllum plant resin, approved for human papilloma virus (HPV)‐induced genital warts. The combination of both ablative Er:YAG laser and topical 0.5% podophyllotoxin solution in hard‐to‐treat palmoplantar HPV warts was investigated.

PATIENTS AND METHODS: Thirty‐five patients with hard‐to‐treat warts (palmar or plantar) with a mean age of (32.2±12.1) years, range 17–50 years, with various pretreatments that had failed, were treated once by Er:YAG laser ablation with a spot size of 3?mm, a frequency between 8?Hz and 10?Hz, and a fluence of 5.7–11.3?J/cm². After wound healing, topical podophyllotoxin 0.5% solution was applied for 3 days followed by a break of 4 days. Four to six treatment cycles with podophyllotoxin were performed.

RESULTS: After laser treatment followed by topical podophyllotoxin cream a complete response was observed in 31 patients (88.6%). Two patients with plantar warts and a complete response showed a relapse within 3 months after treatment (5.7%). None of the patients developed pigmentary changes, wound infections or scarring.

CONCLUSION: The therapy of hard‐to‐treat warts with a combination of Er:YAG laser and topical podophyllotoxin is safe and effective. Compared with laser alone, the CR percentage seems to be higher and the percentage of relapses reduced.     

Successful treatment of chromoblastomycosis caused by Fonsecaea pedrosoi using imiquimod

Chromoblastomycosis (CBM) is a fungal infection caused by fungi belonging to the order Chaetothyriales, and caused mainly by Fonsecaea pedrosoi. The classic treatment, based on itraconazole and/or terbinafine as well as physical approaches, is considered complex and ineffective due to the high rate of relapses. Thus, new strategies are needed to manage CBM; in this regard, the present work reports the evolution of lesions in patients successfully treated with imiquimod. Of note, classic treatment was not effective in healing the lesions of two of them, but single topical treatment with imiquimod healed the lesions.     

Investigation of pregnancy associated plasma protein‐A and neopterin levels in Behçet's patients

Behçet's disease (BD) is an autoimmune disease that affects many organs. We aimed to investigate the relationship between BD and these pregnancy‐associated plasma protein A (PAPP‐A), neopterin, and high sensitive C‐reactive protein (hsCRP) parameters. The study included 57 BD patients and 54 healthy controls. After evaluating the active and inactive disease status of the patients, analyzes were performed. When comparing the patient and control groups, neopterin (111.27 ± 37.49; 76.77 ± 38.27 [nmol/L]; P < .001) and hsCRP (11.81 ± 16.8; 3.62 ± 5.06 [mg/L]; P = .001) parameters were significantly higher in patients. Neopterin (117.68 ± 41.67; 94.85 ± 14.75 [nmol/L]; P = .038) and hsCRP (14.68 ± 18.7; 4.47 ± 7.27 [mg/L]; P = .002) found different in active and inactive patients. The sensitivities of neopterin and hsCRP were also found to be high in BD (respectively 93%, 67%). PAPP‐A was especially elevated in skin pathologies (P = .02) and neopterin in joint involvement (P = .03). We think that the use of neopterin and hsCRP can help in diagnosis and follow‐up of BD.     

Clinical features and natural course of Behçet's disease in 661 cases: a multicentre study

Background Behçet’s disease (BD) is a systemic inflammatory disease with unpredictable exacerbations and remissions. The natural course of BD is not fully known. Objectives We aimed retrospectively to determine the occurrence of the symptoms in chronological order. We also evaluated the influence of the treatment and follow‐up on the clinical severity and tried to identify the factors determining severe organ involvement. Methods Six hundred and sixty‐one patients were involved in this multicentre study. The symptoms of the disease were recorded retrospectively in the time order of the manifestations in each patient. Results Oral ulcers were the most common manifestation (100%), followed by genital ulcers (85·3%), papulopustular lesions (55·4%), erythema nodosum (44·2%), skin pathergy reaction (37·8%), and articular (33·4%) and ocular involvement (29·2%). Oral ulcers were the most common onset manifestation (88·7%). The mean ± SD duration between the onset symptom and the fulfilment of diagnostic criteria was calculated to be 4·3 ± 5·7 years. The clinical severity score was significantly increased in the noncompliant treatment group compared with the compliant group with the passage of time (P < 0·001). The frequency of ocular involvement and genital ulcers was significantly higher in patients whose disease onset was at < 40 years. Genital ulcers, ocular involvement, papulopustular lesions, thrombophlebitis and skin pathergy reaction were found to be significantly more frequent in males. Conclusions Mucocutaneous lesions are the hallmarks of the disease, and especially oral ulcers precede other manifestations. The increase in clinical severity score is more pronounced in patients without regular treatment and follow‐up. Male sex and a younger age at onset are associated with more severe disease.