An overview of cutaneous squamous cell carcinoma imaging diagnosis methods.

Cutaneous squamous cell carcinoma, a type of non-melanoma skin cancer, is a form of keratinocyte carcinoma that stands as one of the most prevalent cancers, exhibiting a rising frequency. This review provides an overview of the latest literature on imaging methods for diagnosing squamous cell carcinoma (SCC) and actinic keratosis (AK). It discusses the diagnostic criteria, advantages, and disadvantages of various techniques such as dermatoscopy, skin ultrasound (US), in vivo and ex-vivo reflectance confocal microscopy (RCM), and line-field confocal optical coherence tomography (LC-OCT). These methods offer benefits including non-invasiveness, rapidity, comprehensive lesion imaging, and enhanced sensitivity, but face challenges like high costs and the need for specialized expertise. Despite obstacles, the use of these innovative techniques is expected to increase with ongoing technological advancements, improving diagnosis and treatment planning for keratinocyte carcinomas. Standardizing LC-OCT imaging algorithms for AK, Bowen's disease, and SCC remains an area for further research.

Orofacial Anomalies in Kindler Epidermolysis Bullosa.

Importance: Kindler epidermolysis bullosa is a genetic skin-blistering disease associated with recessive inherited pathogenic variants in FERMT1, which encodes kindlin-1. Severe orofacial manifestations of Kindler epidermolysis bullosa, including early oral squamous cell carcinoma, have been reported. Objective: To determine whether hypoplastic pitted amelogenesis imperfecta is a feature of Kindler epidermolysis bullosa. Design, Settings, and Participants: This longitudinal, 2-center cohort study was performed from 2003 to 2023 at the Epidermolysis Bullosa Centre, University of Freiburg, Germany, and the Special Care Dentistry Clinic, University of Chile in association with DEBRA Chile. Participants included a convenience sampling of all patients with a diagnosis of Kindler epidermolysis bullosa. Main Outcomes and Measures: The primary outcomes were the presence of hypoplastic pitted amelogenesis imperfecta, intraoral wounds, gingivitis and periodontal disease, gingival hyperplasia, vestibular obliteration, cheilitis, angular cheilitis, chronic lip wounds, microstomia, and oral squamous cell carcinoma. Results: The cohort consisted of 36 patients (15 female [42%] and 21 male [58%]; mean age at first examination, 23 years [range, 2 weeks to 70 years]) with Kindler epidermolysis bullosa. The follow-up ranged from 1 to 24 years. The enamel structure was assessed in 11 patients, all of whom presented with enamel structure abnormalities. The severity of hypoplastic pitted amelogenesis imperfecta varied from generalized to localized pitting. Additional orofacial features observed include gingivitis and periodontal disease, which was present in 90% (27 of 30 patients) of those assessed, followed by intraoral lesions (16 of 22 patients [73%]), angular cheilitis (24 of 33 patients [73%]), cheilitis (22 of 34 patients [65%]), gingival overgrowth (17 of 26 patients [65%]), microstomia (14 of 25 patients [56%]), and vestibular obliteration (8 of 16 patients [50%]). Other features included chronic lip ulcers (2 patients) and oral squamous cell carcinoma with lethal outcome (2 patients). Conclusions and Relevance: These findings suggest that hypoplastic pitted amelogenesis imperfecta is a feature of Kindler epidermolysis bullosa and underscore the extent and severity of oral manifestations in Kindler epidermolysis bullosa and the need for early and sustained dental care.

Ultrasound in non-tumoral pathology of the skin.

Skin ultrasound (US) is a relatively new imaging technique, for which interest has grown significantly in the last decade. Properties such as mobility, real-time imaging and lack of irradiation or sedation, have made it a useful tool in completing the clinical examination. The use of probes of different frequencies has managed to improve the US technique, offering the possibility of obtaining high quality images. Thus, by using high-frequency and ultra-high frequency US, subclinical information can be obtained with a wide applicability in dermatological pathology. In this paper we aim to discuss the main uses of skin US in non-tumoral pathology (inflammatory and autoimmune pathology).

Lymphocyte-predominant lesional inflammatory infiltrates of the skin are associated with mucosal-dominant phenotype in pemphigus.

INTRODUCTION: Pemphigus is a potentially life-threatening autoimmune blistering disease. To date, studies assessing the association of histopathology with clinical phenotype are lacking. We sought to evaluate the main histopathologic findings and, also, the potential links between cutaneous inflammatory infiltrates and clinical characteristics in pemphigus. METHODS: We conducted a retrospective cohort study in patients diagnosed with pemphigus vulgaris (PV) and pemphigus foliaceus (PF) in a referral center for autoimmune blistering diseases. RESULTS: A total of 124 patients were included in the study (97 had PV and 27 had PF). On biopsy specimens, PV was more frequently associated with the "row of tombstones" feature (36.1% vs. 11.1%, p = 0.013), and PF was associated with acanthosis (44.4% vs. 23.7%, p = 0.034). Acantholysis was found in the upper half of the epidermis in PF (96.3% vs. 5.15%, p < 0.001), as opposed to the lower half in PV (75.2% vs. 0%, p = 0.002). Patients with lymphocyte-predominant inflammatory infiltrates in lesional skin specimens presented with a higher frequency of the mucosal-dominant phenotype (25.5% vs. 9.1%, p = 0.014), higher-density cellular infiltrate (100% vs. 41.6%, p < 0.001), and more frequent acantholytic cells (42.6% vs. 23.4%, p = 0.025). Neutrophil-predominant infiltrates in specimens from lesional skin were linked to a milder disease based on median Pemphigus Disease Area Index (38.9% vs. 13.2%, p = 0.036) and Autoimmune Bullous Skin Disorder Intensity Score (20.2 vs. 36.3, p = 0.019), while eosinophil-predominant inflammatory infiltrates were more often associated with eosinophilic spongiosis (100% vs. 23.1%, p = 0.014). CONCLUSIONS: Lymphocyte-predominant infiltrates in lesional skin specimens of pemphigus patients predict a mucosal-dominant phenotype, while neutrophil-predominant infiltrates are associated with a milder disease.

Survival and prognostic factors in bullous pemphigoid: A retrospective cohort study.

Background Bullous pemphigoid is the most common subepidermal autoimmune blistering disease. Till now, the reported prognostic factors in bullous pemphigoid vary considerably. Aims The purpose of this study was to determine the overall survival rate and prognostic factors in bullous pemphigoid. Methods We conducted a retrospective cohort study on newly diagnosed bullous pemphigoid patients between July 2001 and November 2019 in a referral unit for autoimmune blistering skin diseases in Romania. Results One hundred forty-eight patients were included in the study. The Kaplan-Meier overall survival rates at 1, 3, 5 and 10 years were respectively 74.2% (95% confidence interval, 67.5-81.6%), 53.4% (45.7-62.2%), 43.6% (35.9-53%) and 31.3% (23.5-41.7%). The median follow-up among survivors was 48 months (interquartile range: 11-150). Ninety (60.8%) patients died during the follow-up period; of them, 38 (42.2%) had active disease at the time of death. Advanced age, neurological diseases, valvular heart disease, malignancies, use of statins, skin infections and extensive cutaneous involvement were linked to poorer outcomes, while the use of topical corticosteroids was associated with increased overall survival. Limitations This study lacks a control cohort to validate the obtained results. It was conducted in a retrospective manner in a single centre. In addition, indirect immunofluorescence microscopy was not performed in all patients. Conclusion Beyond ageing and neurological comorbidities, the prognosis of bullous pemphigoid patients was significantly influenced by the presence of skin infections, valvular heart disease, use of statins and extensive cutaneous involvement. Topical corticosteroid treatment was associated with increased survival in these patients.

Advancements in Basal Cell Carcinoma Diagnosis: Non-Invasive Imaging and Multimodal Approach.

(1) Background: The aim of this study was to correlate the diagnostic criteria described in dermatoscopy, ultrasonography (US), ex vivo confocal microscopy, and histology to the most common subtypes of basal cell carcinoma (BCC). (2) Methods: We conducted a prospective study including 46 BCC cases, which were analyzed with dermatoscopy using the Delta 30 dermatoscope and Vidix 4.0 videodermoscope, with US using a high-resolution 20 MHz linear probe, with confocal microscopy, along with histopathological analysis. (3) Results: This study categorized BCC by histological subtype, with nodular being the most common (84.8%) and various other subtypes represented. US measurements of tumor thickness correlated strongly with the histopathological depth of invasion index (DI). Dermatoscopy analysis revealed significant associations between specific features and BCC subtypes. The DI was directly related to arborized vessels but inversely related to short, fine telangiectasias, maple-leaf-like areas, and spoke-wheel areas. The presence of ulceration was directly related to the DI. Confocal microscopy images exhibited several characteristics, including fluorescence, nuclear crowding, peripheral palisading, clefting, increased nuclear-cytoplasmic (N/C) ratio, and a "cauliflower-like" appearance. (4) Conclusion: The advanced detection of BCC through imagistic techniques like dermatoscopy, confocal microscopy, and ultrasound improves the diagnosis and may offer valuable insights for treatment in the future by evaluating lesion characteristics.

Challenges and pitfalls between lichen planus pemphigoides and bullous lichen planus.

Lichen planus pemphigoides (LPP) and bullous lichen planus (BLP) are rare dermatoses, which are characterised by blisters and lichenoid lesions. Their clinical presentation is heterogenous, displaying overlapping features or mimicking other dermatological diseases. Therefore, diagnosis can often be challenging, requiring a thorough dermatological examination along with distinctive histological and immunopathological characteristics. Lichenoid degeneration of the basal epidermis exposes various antigens of the dermal-epidermal junction in LPP, resulting in the breakdown of immune tolerance, hence, the production of autoantibodies against type XVII collagen. Conversely, no pathogenic autoantibodies are detected in BLP. However, some cases of mucosal lichen planus might display immunopathological features suggestive of autoimmune blistering diseases. Therefore, a better understanding of the pathophysiology of these two distinct dermatoses is imperative. The aim of this review was to provide a summary of the current knowledge on the clinical hallmarks, diagnosis and available therapeutic options in LPP and BLP.

Phänotypisches und genetisches Spektrum von Incontinentia pigmenti - eine große Fallserie.

HINTERGRUND: Incontinentia pigmenti ist eine seltene X-chromosomal dominant vererbte Systemerkrankung, die vor allem die Haut, aber auch andere neuroektodermale Gewebe wie Zähne, Haare, Augen und das zentrale Nervensystem betrifft. PATIENTEN UND METHODIK: Diese multizentrische Fallserienstudie wurde an drei europäischen Hautkliniken durchgeführt und umfasste 30 Patienten mit Incontinentia pigmenti. Zwanzig Patienten wurden klinisch und genetisch untersucht, weitere zehn nur genetisch. ERGEBNISSE: Die Studie umfasste 28 Frauen und zwei Männer mit einem medianen Alter von drei Jahren. Kutane Manifestationen zeigten sich bei allen 20 Patienten mit klinischen Daten. Stadium I wurde in 90 % dieser Patienten beobachtet. Stadium IV wurde bereits im Alter von einem Jahr beobachtet. Zahn- (81 %), Haar- (78 %) und neurologische Anomalien (53 %) waren häufiger als in bisherigen Berichten. Vierzehn Hautbiopsien zeigten typische Merkmale des entsprechenden Stadiums. Genetische Tests wurden bei 24 Patienten durchgeführt, von denen 14 die häufige Exon 4-10-Deletion und sieben andere pathogene Varianten aufwiesen, darunter drei unveröffentlichte Mutationen. In drei weiteren Fällen wurden keine genetischen Veränderungen gefunden. SCHLUSSFOLGERUNGEN: In dieser Studie reichte der Phänotyp von lediglich subtil ausgeprägter Hautbeteiligung bis hin zu schweren Multisystemerkrankungen. Die extrakutane Beteiligung sollte zum Zeitpunkt der Diagnose und in regelmäßigen Abständen evaluiert werden, da sich einige Manifestationen erst mit der Zeit entwickeln. SUMMARY: Background and objectives Incontinentia pigmenti is a rare X-linked dominantly inherited systemic disease affecting primarily the skin but also other neuroectodermal tissues such as teeth, hair, eyes, and the central nervous system. Patients and methods This multicenter case series study was conducted at three European departments of Dermatology including 30 patients with incontinentia pigmenti. Twenty patients were evaluated clinically and genetically, another ten only genetically. Results The study included 28 females and two males with a median age of three years. Cutaneous manifestations were present in all 20 patients with clinical data. Stage I was observed in 90 % of those patients. Stage IV was observed as early as one year of age. Dental (81 %), hair (78 %) and neurological anomalies (53 %) were more frequent than previously reported. Fourteen skin biopsies showed typical features of the corresponding stage. Genetic testing of 24 patients revealed the common exon 4-10 deletion in 14 cases and seven other pathogenic variants, including three unpublished mutations. In another three cases, no genetic alterations were found. Conclusions In this study, the phenotype ranged from only subtle cutaneous involvement to severe multisystemic disorders. Extracutaneous involvement should be evaluated at the time of diagnosis and in regular intervals, as some manifestations may develop over time.

Phenotypic and genetic spectrum of incontinentia pigmenti - a large case series.

BACKGROUND AND OBJECTIVES: Incontinentia pigmenti is a rare X-linked dominantly inherited systemic disease affecting primarily the skin but also other neuroectodermal tissues such as teeth, hair, eyes, and the central nervous system. PATIENTS AND METHODS: This multicenter case series study was conducted at three European departments of Dermatology including 30 patients with incontinentia pigmenti. Twenty patients were evaluated clinically and genetically, another ten only genetically. RESULTS: The study included 28 females and two males with a median age of three years. Cutaneous manifestations were present in all 20 patients with clinical data. Stage I was observed in 90 % of those patients. Stage IV was observed as early as one year of age. Dental (81 %), hair (78 %) and neurological anomalies (53 %) were more frequent than previously reported. Fourteen skin biopsies showed typical features of the corresponding stage. Genetic testing of 24 patients revealed the common exon 4-10 deletion in 14 cases and seven other pathogenic variants, including three unpublished mutations. In another three cases, no genetic alterations were found. CONCLUSIONS: In this study, the phenotype ranged from only subtle cutaneous involvement to severe multisystemic disorders. Extracutaneous involvement should be evaluated at the time of diagnosis and in regular intervals, as some manifestations may develop over time.

Ketoconazole-p aminobenzoic cocrystal, an improved antimycotic drug formulation, does not induce skin sensitization on the skin of BALBc mice.

Fungal infections are a growing global health problem. Therefore, our group has synthetized and characterized an improved antimycotic by co-crystallization of ketoconazole and para-amino benzoic acid, named KET-PABA. The aim was to increase bioavailability, biocompatibility, and efficiency of the parent drug-ketoconazole. Based on our previous results showing the cocrystal improved physical properties, such as stability in suspension, solubility, as well as antimycotic efficiency compared to ketoconazole, the current study investigated the local possible side effects induced on the skin of BALBc mice by the application of KET-PABA cocrystal, in view of a further use as a topically applied antimycotic drug. A specific test (mouse ear-swelling test) was used, combined with the histopathological examination and the measurement of pro and anti-inflammatory cytokines and inflammation mediators. KET-PABA application was safe, without signs of skin sensitization shown by the mouse ear sensitization test, or histopathology. KET-PABA strongly inhibited proinflammatory cytokines such as IL1 α, IL1 ß, IL6 and TNF α, and other proinflammatory inducers such as NRF2, compared to vehicle. KET-PABA had no effect on the levels of the anti-inflammatory cytokine IL10, or proinflammatory enzyme COX2 and had minimal effects on the activation of the NF-κB pathway. Overall, KET-PABA application induced no sensitization, moreover, it decreased the skin levels of proinflammatory molecules. The lack of skin sensitization effects on BALBc mice skin along with the inhibition of the proinflammatory markers show a good safety profile for topical applications of KET-PABA and show promise for a further clinical use in the treatment of cutaneous mycosis.

[Treatment of pigmentation disorders in association with systemic diseases]. / Therapie von Pigmentstörungen in Zusammenhang mit systemischen Erkrankungen.

Pigmentation disorders are a frequent skin problem and incorporate a broad spectrum of diseases, caused by an abnormal melanin pigmentation or also non-melanin pigmentation of the skin. Both hypermelanosis and hypomelanosis can be hereditary or acquired. This article summarizes the treatment approaches that are used in the majority of acquired pigmentation disorders of the skin. The following forms of hypermelanosis are addressed: lentiginosis, hyperpigmentation due to endocrine disorders or other systemic diseases, drug-induced hyperpigmentation. Acquired hypomelanoses include postinflammatory hypomelanosis, chemical depigmentation, idiopathic guttate hypomelanosis and punctate leucoderma. With reference to non-melanin pigmentation, the exogenous pigmentation due to chemicals, metals and drug exposure are discussed. The treatment is primarily based on finding the cause of the alterations to the pigment. The affected area, age and ethnic origin are also important factors. The spectrum of therapeutic options is broad: topical agents, chemical peeling, systemic agents, laser and light-based treatment. As some of these treatment procedures can have side effects, the availability of a protocol that contains information on the drug concentration, dose, parameters for laser treatment and the number of sessions is important. For every disorder the specific dermatological treatment is presented even when some pigmentation alterations that occur in association with systemic diseases, are cured by the treatment of the primary disease. Most diseases are exacerbated by exposure to UV light. Therefore, sun protection is recommended and a cosmetic coverage is indicated.

A Recurrent Case of Targetoid Hemosiderotic Hemangioma: A Case Report and a Comprehensive Review of the Literature.

Targetoid hemosiderotic hemangioma is an acquired vascular malformation of unknown origin. We report the case of a 31-year-old man with a recurrent and spontaneous regressive targetoid hemosiderotic hemangioma. Diagnosis relied on clinical and histological findings. Physical examination revealed presence of an approximately 2 cm targetoid lesion located on the left arm, and associated with pain after pressure. No trigger agent (trauma, insect sting) was reported. Dermoscopy showed a group of red lacunae centrally, encircled by an intermediate yellow circular homogenous area and a red violaceous homogenous ring in the periphery. The histopathological examination and the immunohistochemical staining of the lesion were characteristic for a hemangioma-like proliferation of vessels in the upper part of the dermis, similar to a targetoid hemosiderotic angioma. We also review epidemiological, clinical, and histopathological findings in 6 similar cases presented in the literature. Spontaneous regression and recurrence have rarely been described in this type of skin lesion.

Effects of silver and gold nanoparticles phytosynthesized with Cornus mas extract on oral dysplastic human cells.

Background: Oral cancer is highly aggressive due to difficult diagnosis, therapy resistance and increasing frequency; thus finding prevention therapies is very important. Aim: This study evaluates the use of gold and silver nanoparticles (NPs), phyto-synthesized with Cornus mas extract against oral dysplastic lesions. Methods: NPs were characterized by UV-Vis, Fourier-transform infrared spectroscopy, transmission electron microscopy, x-ray diffraction and laser Doppler microelectrophoresis. Biological testing employed two human oral cell lines: gingival fibroblasts and dysplastic keratinocytes and evaluated viability, cell death mechanisms and cellular uptake. Results: NPs induced selective toxic effects against dysplastic cells. p53/BAX/BCL2 activation and PI3K/AKT inhibition led to cell death through necrosis and apoptosis. NPs also induced antioxidant and anti-inflammatory effects. Conclusion: NPs of gold and silver showed promising beneficial effects in the therapy of oral dysplasia.

Risk factors for melanoma and skin health behaviour: An analysis on Romanian melanoma patients.

In contrast to Western Europe, in Central and Eastern Europe reports show higher rates of advanced melanoma and lower survival. Our aim was to document and compare melanoma risk factors and skin health behaviour in patients diagnosed with melanoma and people not affected by this disease in a large medical university centre from Romania (Cluj-Napoca). Two hundred and forty-seven melanoma patients followed-up in the Department of Dermatology at the Cluj-Napoca Emergency County Hospital and 956 people not affected by melanoma completed a paper-based questionnaire regarding melanoma risk factors, risk behaviour and self-protecting measures, after giving informed consent. People with melanoma had significantly higher personal risk and protective behaviour, and lower risk behaviour than those not affected. Although our data suggest that melanoma patients are better educated about how to avoid a second primary melanoma, our results are concerning when compared with studies from other countries. The low incidence of self and clinical skin-examination together with the relatively low percentage of participants which would consult a doctor in the case of new/changing mole could be one of the explanations for the late diagnosis of melanoma in the studied population. According to our findings, there is an urgent need for population health campaigns regarding not only primary but also secondary melanoma prevention.

Progesterone hypersensitivity: Case report with favorable evolution.

Progesterone hypersensitivity or autoimmune progesterone dermatitis is characterized by heterogeneous skin eruptions that cyclically aggravate during the second half of the menstrual cycle, corresponding to a rise in the progesterone level. Clinical presentation is highly variable and includes all urticaria manifestations with or without angioedema, vesiculobullous, eczematous, purpuric or target-like lesions on the skin and mucous membrane. Both endogenous progesterone as well as exogenous progestogens may represent an initial trigger. We report a case of progesterone hypersensitivity in a 27-year old woman with favorable evolution only on topical therapy, the positive clinical outcome being maintained during a subsequent pregnancy and postpartum period.

Unusual Manifestations of Secondary Syphilis: Case Presentations.

Dear Editor, Syphilis is an infection caused by Treponema pallidum. Without treatment, it goes through the following stages: primary, secondary, latent, and tertiary (1). The clinical picture of secondary syphilis is very variable (2,3). We present two rare cases of secondary syphilis, one with nodular lesions initially considered to be lymphoma and second with periostitis, which was initially interpreted as an osteoma. To date, only 15 cases with nodular lesions and 10 cases with periostitis in secondary syphilis have been reported in the literature. The first patient was a 59 year old man who presented in a private practice with nodular lesions on the face and axillary and inguinal folds (Figure 1, a, b). The initial diagnostic consideration was lymphoma. A biopsy specimen was taken, and the histopathological features revealed epidermal hyperplasia with papillomatosis, minimal spongiosis with many neutrophils and with a marked inflammatory infiltrate in dermis, consisting of lymphocytes, plasma cells, and neutrophils; the diagnosis of interfaced dermatitis was established (Figure 1, d, e). After one month, the patient presented to our clinic with numerous nodular lesions, some of them painful, located on the trunk and intertriginous folds, including the intergluteal cleft - the lesions in this area being suggestive of condylomata lata (Figure 1, c). The diagnosis of secondary syphilis was taken into consideration, and screening serum tests were performed and found reactive: a Venereal Diseases Research Laboratory (VDRL) titer of 1:64 and Treponema pallidum Hemaglutination Assay (TPHA) titer of 1:80. Hepatitis and anti-human immunodeficiency virus (HIV) antibodies serology was negative. The biopsy was repeated and showed the same histopathological changes. In addition, Warthin-Starry staining was performed, revealing the presence of some spiral micro-organisms in the dermis corresponding to Treponema pallidum (Figure 1, f). A diagnosis of secondary syphilis was established, and the patient was treated with benzathine penicillin G 2.4 million units by intramuscular injection once a week for 2 consecutive weeks. The skin lesions regressed within 1 month, and serological tests showed a VDRL titer of 1:8 3 months after treatment. The second patient was a homosexual male, 35 years old, diagnosed with HIV infection, stage B2. He presented with bone pain in the calves and forearms, with insidious onset. He also presented with an associated erythematous maculo-papular rash on the trunk and limbs and generalized lymphadenopathy (Figure 2, a, b). The tibial crest and radius were sensitive to palpation. A right leg radiography was performed, raising suspicion of osteoid osteoma. The CT scan excluded the diagnosis of osteoma; taking into account the epidemiological context, the diagnosis of syphilis was suspected. The diagnosis was confirmed by leg ultrasound examination (2D US) which showed thickening of the compact tibial bone associated with subperiosteal destructive and proliferative changes (Figure 2, c, d) and by serology for syphilis: the VDRL titer was 1:32 and the TPHA titer was 1:80. The patient was treated with benzathine penicillin 2.4 million units, once a week, for 2 consecutive weeks, with clinical improvement. Syphilis continues to be a serious public health problem worldwide, even if it is a controllable disease due to diagnostic tests and effective and accessible treatment. According to the World Health Organization in 2008, the estimated number of new cases of sexually transmitted diseases in adults with syphilis is 10.6 million cases (4). The cases presented in this paper were characterized by unusual manifestations, requiring good collaboration between the dermatologist and other specialties. In the first case, the diagnosis of secondary syphilis was confirmed by positive serological, clinical, and histopathological findings. The main differential diagnosis of nodular syphilis includes lymphoma, sarcoidosis, Kaposi's sarcoma, atypical mycobacteriosis, deep fungal infections, leprosy, tuberculosis, leishmaniasis, and lymphomatoid papulosis (5). Another important differential diagnosis is between secondary and tertiary syphilis, especially when ulcerating nodules are present. Tertiary syphilis is characterized by unilateral, deep ulcerating nodules with necrotizing granulomas (6). Bone involvement during syphilis is mainly represented by polyarthritis, synovitis, osteitis, and periostitis (7,8). Syphilitic periostitis is characterized by localized or diffuse pain, particularly during the night, which is relieved by movement. The skull, the shoulder girdle, and the long bones are the most common sites of involvement (9). In conclusion, we presented two different cases of secondary syphilis that contribute to the clinical experience of rare cases presented in the literature, raising the awareness of dermatologists and other specialists about less specific clinical aspects of syphilis.

Molecular diagnosis of anti-laminin 332 (epiligrin) mucous membrane pemphigoid.

BACKGROUND: Mucous membrane pemphigoid is a group of chronic subepithelial autoimmune blistering diseases that mainly affect mucous membranes. Laminin 332-specific autoantibodies are present in approximately 1/3 of the patients, being associated with an increased risk of malignancy. Because of the severe complications, an early recognition of the disease allowing a timely therapy is essential. The gold standard methods for detection of laminin 332-specific autoantibodies, including the immunoprecipitation and immunoblotting are non-quantitative, laborious and restricted to a few specialized laboratories worldwide. In addition, the use of radioimmunoassays, although highly sensitive and specific, are laborious, expensive and tightly regulated. Therefore, there is a stringent need for a quantitative immunoassay for the routine detection of laminin 332-specific autoantibodies more broadly available to diagnostic laboratories. The aim of this study was to compare different antigenic substrates, including native, recombinant laminin 332 and laminin 332-rich keratinocyte extracellular matrix, for development of an ELISA to detect autoantibodies in mucous membrane pemphigoid. RESULTS: Using a relatively large number of sera from MMP patients with well-characterized autoantibody reactivity we show the suitability of ELISA systems using laminin 332 preparations as adjunct diagnostic tools in MMP. While glycosylation of laminin 332 does not appear to influence its recognition by MMP autoantibodies, ELISA systems using both purified, native and recombinant laminin 332 demonstrated a high sensitivity and good correlation with the detection of autoantibodies by immunoblotting. ELISA systems using different laminin 332 preparations represent a feasible and more accessible alternative for a broad range of laboratories. CONCLUSIONS: Our findings qualify the use of immunoassays with the laminin 332-rich preparations as an ancillary diagnostic tool in mucous membrane pemphigoid.

A novel IKBKG mutation in a patient with incontinentia pigmenti and features of hepatic ciliopathy.

We describe a new mutation in exon 4 of IKBKG, encoding nuclear factor-kappa B in a patient with incontinentia pigmenti. The patient had a severe cholestatic liver disease with features of a ciliopathy and underwent liver transplantation. We cannot establish a link between incontinentia pigmenti, a very rare disease, and hepatic ciliopathy, but we suggest that hepatic evaluation should be considered in patients with incontinentia pigmenti.

Role of physical factors in the pathogenesis of bullous pemphigoid: Case report series and a comprehensive review of the published work.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease affecting mainly the elderly. The subtype of the disease induced by physical agents represents a rare and, therefore, insufficiently characterized form. In the present study, we aimed to contribute to a better understanding of the pathogenetic mechanisms involved in the onset of BP induced by different trigger factors. We have retrospectively analyzed nine cases of BP. All patients were characterized based on clinical, epidemiological and immunological parameters. For each case, the trigger factor involved was specified. In addition to our retrospective analysis, a comprehensive review of the 59 published cases was conducted, regarding the involvement of trigger factor in BP, and clinical, epidemiological and immunological data were collected. In the local study, conducted on nine patients diagnosed with BP, various trigger factors were identified: contrast substance injection, surgical procedure, mechanical trauma, insect bite, thermal burn, radiotherapy and ultraviolet exposure associated with pre-existing psoriasis. The autoantibodies from all patients were shown to activate granulocytes and induce dermal-epidermal split. Different hypotheses regarding the pathogenetic mechanism involving the trigger factors have been discussed. In regard of the pathogenetic mechanism, we believe that the most reliable hypothesis is that BP patients already have low titers of anti-basement membrane autoantibodies which activate the granulocytes. However, more studies are needed for a better understanding of the pathogenetic mechanism of the intervention of trigger factors.