Isotretinoin-associated acne fulminans: A multicentre, retrospective study of the European Academy of Dermatology and Venereology Task Force on Acne, Rosacea and Hidradenitis Suppurativa.

BACKGROUND: Acne fulminans (AF) is a rare severe acne entity. Although occasionally reported, it is unclear whether AF development is associated with oral isotretinoin treatment. OBJECTIVES: To investigate the occurrence of isotretinoin-associated AF, clinical characteristics and prognosis at follow-up. METHODS: An international, multicentre, retrospective study was performed in eight hospitals following the call of the EADV Task Force on Acne, Rosacea and Hidradenitis Suppurativa (ARHS). Characteristics of patients treated with isotretinoin before the development of AF (isotretinoin-associated acne fulminans, IAF) were compared with non-IAF (NAF). RESULTS: Forty-nine patients diagnosed with AF from 2008 to 2022 were included (mean age 16.4 years, SD 2.9, 77.6% male). Αrthralgias/arthritis occurred in 11 patients (22.9%). AF occurred without any previous acne treatment in 26.5% of the patients. Overall, 28 patients (57.1%) developed AF after oral isotretinoin intake (IAF group), while the remaining 21 patients (42.9%) developed AF without previous oral isotretinoin administration (NAF group). IAF occurred after a median duration of isotretinoin treatment of 45 days (IQR: 30, 90). Patients with IAF were more frequently male compared to patients with NAF (89.3% vs. 61.9%, respectively, p = 0.023). There were no differences in patients with IAF versus NAF in patient age, the duration of pre-existing acne, a family history of AF, the distribution of AF lesions or the presence of systemic symptoms or arthralgias. Regarding the management of AF, patients with IAF were treated more frequently with prednisolone (96.2%) compared to those with NAF (70%; p = 0.033) and less frequently with isotretinoin (32.1%) compared to NAF (85.7%; p < 0.001). At a median follow-up of 2.2 years, 76.4% of patients were free of AF and scarring was present in all patients. CONCLUSIONS: No specific clinical or demographic characteristics of IAF compared with NAF could be detected, a fact that does not support IAF as a district clinical entity.

Immunohistochemical analysis of the ligamentum mucosum is the key to understand its clinical usefulness.

Ligamentum Mucosum(LM) is a ligamentous structure within the synovial layer of the knee joint capsule. For a long time LM was perceived as the vestigial remnant from the embryological development of the knee. Being treated as an irrelevant structure LM was often the first victim of shaver during arthroscopy. However, last years have shown increased interest in this structure due to its potentially significant clinical role. Our aim was to classify LM based on its morphological characteristics and examine its microanatomy using immunohistochemical analysis to reveal the potential clinical value for surgeons. We have examined sixteen fresh frozen lower limbs, 6 females (mean age 83.1 ± 3.4 years) and 10 males (mean age 84.2 ± 6.8 years). Classical histological H+E stain was routinely conducted. Subsequently, CD31 antibody (DAKO, Monoclonal Mouse Anti-Human, Clone JC70A) was used to mark vascular epithelium. Monoclonal Mouse Anti-Human Neurofilament Protein (NFP) antibody (DAKO, Clone 2F11) was used to expose the nerves. Moreover, we have conducted arthroscopic visualizing and suturing LM to the torn ACL during routinely performed arthroscopic suturing of the ACL. The dissection process has revealed that LM was present only in 75% of cases. Histological examination confirmed the presence of longitudinal collagen fiber bundles in all samples. Tiny nerves were confirmed by NFP, along the subsynovial layer in all samples. CD-31 immunostain revealed the presence of many vascular vessels along the entire ligament, especially well developed at its distal end. Our study has revealed that LM contains rich vascular network. Thus, it may be a donor for the revascularization process after ACL tear or reconstruction which may improve the recovery. Another great advantage of the LM is the presence of nerves along the subsynovial layer, hopefully they may serve as the source of reinnervation and hence better clinical outcome. Based on our results we believe that seemingly irrelevant LM may be very useful during surgical procedures in the knee region. Suturing LM to the ACL may not only prevent the infrapatellar fat pad from subluxation but also improve the blood flow and reinnervation of the injured ACL. Until now there are only a few studies examining microanatomy of the LM. This basic knowledge may serve as the foundation for surgical procedures. Hopefully our findings may be useful for surgeons while planning surgical procedures or clinicians while diagnosing patients who suffer anterior knee pain.

Microanatomical study of arachnoid granulations and meningeal architecture around Meckel's cave.

Although the microanatomy of Meckel's cave (MC) has been well studied, there are still controversies regarding the meningeal architecture of the space. Moreover, there are only general mentions of the arachnoid granulations near MC in just a few sources. This study is aimed at determining the frequency, location, and anatomical variability of the main clusters of arachnoid granulations around MC. The dissection involved 26 isolated specimens of MC fixed in formalin (neutral buffered, 10%). This number included five freshly harvested specimens examined histologically. Additional paraffin block with MC horizontal section was taken from our neuroanatomical collection. Carefully selected anatomical and histological techniques were applied to assess the complex relationships between the arachnoid granulations and adjacent structures. Arachnoid granulations were found around MC in all specimens with different anatomical variations. The main clusters of arachnoid granulations were close to the trigeminal ganglion and its divisions. The dorsolateral wall of MC was a thick layer formed by interweaving bundles of collagen fibers arranged in various directions. The entire MC was surrounded by a dural sleeve (envelope). This sleeve separated MC from the lateral sellar compartment. At its anterior (rostral) end, it formed a cribriform area pierced by individual fascicles of the trigeminal nerve's primary divisions. The connective tissue forming the sleeve was not only continuous with the epineurium but also shifted to the perineuria surrounding individual nerve fascicles. The meningeal architecture around MC has a complex and multilayer arrangement with a collagenous sleeve closely related to the trigeminal ganglion. Arachnoid granulations are typically found around MC.

A Multicenter Cohort Study Evaluating the Teratogenic Effects of Isotretinoin on Neonates.

(1) Background: Isotretinoin (ISO) is a systemic retinoid known for its teratogenic effects on embryos and fetuses. The aim of this study was to compare the pregnancy outcomes of women who were exposed to isotretinoin with those of women without such exposure from a teratogenic point of view. (2) Methods: A total of 1459 female patients from three clinical hospitals in Poland and Romania, segregated into two groups depending on their ISO exposure, were evaluated between January and December 2019. Medical records were screened to identify the pregnancy outcomes and congenital malformation rates. (3) Results: The congenital malformation rate for the exposed group was 1.2% (four cases), and no specific signs of Accutane embryopathy were identified. Women from the unexposed group were more likely to deliver preterm and through cesarean deliveries and had a higher rate of newborn congenital malformations as compared to women from the exposed group. (4) Conclusions: Even though we could not find a significant association between ISO exposure and teratogenic effects in newborns, effective contraceptive measures are key to preventing unfavorable pregnancy outcomes.

The use of isotretinoin in acne therapy in early childhood and its effect on the occurrence of acne symptoms later in life. Eight-year follow-up.

Introduction: Acne vulgaris is a chronic inflammatory skin disease of the pilosebaceous follicles that affects patients of all ages. Aim: Use of isotretinoin in the early stages of the disease to prevent subsequent lesions of acne, including prolonged treatment and acne scars at a later age. Material and methods: A retrospective, comparative study was carried between January 2010 and November 2018. The study population consisted of 90 children aged 9-18 years with acne. During treatment by isotretinoin the clinical evaluation was done every month. Patients were divided into three groups according to age. One of the qualification criteria was follow-up visits. Results: A total of 90 children (67.8% females; mean age: 13.5 years) were enrolled. In group A (30 individuals - aged 9-11) and B (30 individuals - aged 12-13), treatment was terminated 2 months after clinical improvement (mean: 3 months). In control group C (30 individuals - aged 14-18), treatment was carried out using average cumulative dose 135 mg/kg bw/day. All groups showed up for follow-up. after 1 to 8 years. In groups A and B, 13 people underwent a second acne treatment; in 3.33% oral isotretinoin was used, in 18.33% topical treatment. In group C, 30 (100%) individuals underwent a second acne treatment; in 20% oral isotretinoin was used, and 80% required a topical treatment. Acne scars and post acne hyperpigmentation have been documented in 73.33% in group C. Conclusions: Early, reasonable and short-term use of isotretinoin can reduce the incidence of acne in the future and reduce the occurrence of secondary acne symptoms.

Cutaneous and hypersensitivity reactions associated with COVID-19 vaccination-a narrative review.

Vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV­2) has become a major tool in the battle against the coronavirus disease 2019 (COVID-19) pandemic. Numerous products have been developed and more are to come. Vaccination success varies greatly between different countries. There are a number of different vaccine types, such as mRNA, DNA vaccines, adenovirus vector vaccines, and full-length spike protein nanoparticles with a special matrix. The different types may also cause a different spectrum of adverse events. With mass vaccination, post-marketing surveillance for product safety becomes increasingly important. In this review, we discuss possible hypersensitivity and cutaneous adverse events related to SARS-CoV­2 vaccination-from local reactions like COVID arm to systemic and severe reactions like anaphylaxis. Vaccination may also induce or exacerbate preexisting disorders such as herpes zoster infection. This review should provide information to tailor, whenever possible, vaccination to patients' needs. It is a contribution to patient safety as well. There is general consensus that the benefits of SARS-CoV­2 vaccination currently outweigh the risks of possible adverse events.

Gross and Micro-Anatomical Study of the Cavernous Segment of the Abducens Nerve and Its Relationships to Internal Carotid Plexus: Application to Skull Base Surgery.

The present study aims to provide detailed observations on the cavernous segment of the abducens nerve (AN), emphasizing anatomical variations and the relationships between the nerve and the internal carotid plexus. A total of 60 sides underwent gross-anatomical study. Five specimens of the AN were stained using Sihler's method. An additional five specimens were subjected to histological examination. Four types of AN course were observed: a single nerve along its entire course, duplication of the nerve, division into separate rootlets at the point of contact with the cavernous part of the internal carotid artery (ICA), and early-branching before entering the orbit. Due to the relationships between the ICA and internal carotid plexus, the cavernous segment of the AN can be subdivided into a carotid portion located at the point of contact with the posterior vertical segment of the cavernous ICA and a prefissural portion. The carotid portion of the cavernous AN segment is a place of angulation, where the nerve always directly adheres to the ICA. The prefissural portion of the AN, in turn, is the primary site of fiber exchange between the internal carotid plexus and either the AN or the lateral wall of the cavernous sinus.

Microsurgical Anatomy of the Inferomedial Paraclival Triangle: Contents, Topographical Relationships and Anatomical Variations.

The inferomedial triangle is one of the two surgical triangles in the paraclival subregion of the skull base. It is delineated by the posterior clinoid process, the dural entrance of the trochlear nerve and the dural entrance of the abducens nerve. The aim of the present article is to describe the anatomical variations within the inferomedial triangle. Measurements of the triangle's borders and area were supplemented by detailed observations of the topographical anatomy and various arrangements of its contents. Nine adult cadaveric heads (18 sides) and 28 sagittal head sections were studied. The mean area of the inferomedial triangle was estimated to be 60.7 mm2. The mean lengths of its medial, lateral and superior borders were 16.1 mm, 11.9 mm and 10.4 mm, respectively. The dorsal meningeal artery was identified within the inferomedial triangle in 37 out of 46 sides (80.4%). A well-developed petrosphenoidal ligament of Grüber was identified within the triangle on 36 sides (78.3%). Although some structures were variable, the constant contents of the inferomedial triangle were the posterior petroclinoid dural fold, the upper end of the petroclival suture, the gulfar segment of the abducens nerve and the posterior genu of the intracavernous internal carotid artery.

Malignant Degeneration of Scars.

"Marjolin's ulcer" is known as malignant degeneration of ancient burn scars, but both words can induce misdiagnosis. Malignant degeneration of scarring tissue can occur and can vary in its clinical, histological manifestations and its pre-existing skin lesions. We present several cases to substantiate our observations. "Marjolin's ulcer" is not synonym to an ulceration appeared on an old burn scar, transformed into squamous cell carcinoma.

Immunomodulatory drugs alone and adjuvant to surgery for hidradenitis suppurativa/acne inversa-A narrative review.

Hidradenitis suppurativa/acne inversa (HS/AI) is one of the most debilitating dermatoses with a strong negative impact on every dimension of quality of life. Treatment is dependent on the severity of clinical manifestations and comorbidities. While anti-inflammatory and antimicrobial approaches are recommended for mild and moderate stages, immunomodulatory drugs have gained increasing interest in all stages of HS/AI. We reviewed the available data on this subject in a narrative review and included not only substances with published final outcome but those where either the ongoing trials or experience from case report. Furthermore, we investigated combined surgical therapy and immunomodulatory drugs and raised specific questions to be answered in controlled settings. This aspect seems to be underrepresented. The first approved medical treatment for HS/AI is adalimumab. Other cytokine, interleukin, Janus kinase and C5a inhibitors and antagonists are under investigation. IL-1 inhibitors and antagonists may become an option for mild to moderate HS/AI, while most of the other medical compounds target moderate to severe HS/AI. Despite medical efforts with immunomodulatory agents, surgery remains a cornerstone of efficient HS/AI therapy. Better outcome in advanced disease might be achieved by combining drug therapy and surgery, but more systematic clinical trials are necessary for the optimal combination.

Anatomical variations and innervation patterns of the superior oblique muscle.

GOAL: The location and anatomical relationships of the superior oblique muscle make surgical intervention difficult. The aim of the present paper was therefore to supplement existing anatomical descriptions of this muscle. Its anatomical variability is particularly emphasized, including variations in muscle and tendon size and details of the innervation pattern. MATERIALS AND METHODS: The study was conducted on 78 orbits from 39 adult human cadavers of both sexes (18 males and 21 females). The roof and upper part of the medial and lateral walls of the orbit were carefully removed, which allowed the superior oblique muscle and trochlear nerve to be exposed along their entire course. Sihler's stain was applied to visualize the intramuscular distribution of the trochlear nerve. RESULTS: The length of the muscle between the origin and trochlea ranged from 37.8 to 56.5mm, the length of the tendinous expansion ranged from 16.3 to 22.8mm, and the width of the scleral insertion of the muscle's tendon ranged from 5.4 to 9.6mm. In two cadavers, accessory muscular slips connecting the levator palpebrae superioris muscle to the trochlea of the superior oblique muscle were present unilaterally. The distance from the level of the trochlea attachment to the anteriormost endings of the intramuscular branches varied from 17.2 to 21.5mm. CONCLUSIONS: The intramuscular nervous branches of the trochlear nerve form a tree-like pattern. Unexpected anatomical variations such as accessory muscular bands could be relevant during orbital imaging or surgeries.

Crusted (Norwegian) scabies as a strong marker of adult T-cell leukemia/lymphoma in HTLV-1 infection.

We present a rare case of crusted scabies in an human T-cell lymphotropic virus type 1 (HTLV-1) infected woman prior to onset of adult T-cell leukemia/lymphoma (ATL). We highlight the importance of this rare form of scabies as a prediagnostic sign of ATL, requiring high suspicion and monitoring of possible symptoms for early detection of ATL.

The value of metastasectomy in stage IV cutaneous melanoma.

Cutaneous melanoma is an aggressive neoplasia of melanocytes. Prognosis is dependent on tumor stage. Stage IV melanoma is characterized by the occurrence of distant metastases. Response of metastases to classical chemotherapy is limited and toxicity of treatment is high. In recent years, new developments in immunotherapy and targeted therapies improved prognosis of stage IV melanoma patients with better tolerability of treatment. There is no dispute about surgical treatment of primary melanoma. But what is the value of metastasectomy in the era of new systemic treatments? This review aims to discuss available data for surgical removal of distant metastases for several organs and tissues. The available evidence suggests that for selected patients with possible complete resection of all tumor metastases, metastasectomy remains an effective treatment option with a benefit in overall survival.

Aesthetic dermatology: What's new, what's true?

Aesthetic dermatology (AD) is a rapidly growing subspecialty of dermatology. The acceptance of AD in scientific community and the society is associated with its competence, efficiency, and seriousness. This review highlights some recent developments toward new tools, techniques, and understanding in the field of AD. Analyzing the specific needs of patients and assessing the effect by objective measurements is important for further progress. For long time ignored, white adipose tissue has gained increasing interest in biology and rejuvenation. Characterization of dermal and subcutaneous white adipose tissue has made progress. The interaction of hyaluronic acid and calcium hydroxyl apatite (CaHA) fillers with adipocytes could be responsible for clinical efficacy. New developments of oral collagen treatment and highly diluted CaHA to contour the body outside the face will be discussed. Submental contouring using purified desoxycholic acid is another new development.

Adverse effects of isotretinoin: A large, retrospective review.

Acne is a very common and disfiguring disease that affects mostly adolescents and, to some extent, adults. The objective of our study was to estimate the adverse effects after isotretinoin by treatment of 3,525 patients due to acne vulgaris in a 5-year observation. Retrospective, comparative study was carried out in Poland and Romania from January 2012 to August 2016. Inclusion criteria into this study were moderate, severe, and nodulocystic inflammatory acne vulgaris. Exclusion criteria were mild acne, pregnant, and lactating women. Statistical analysis was carried out using T test and Chi square. All patients were treated with oral isotretinoin. Patient age ranged from 13-35 years. Dry lips was the most commonly reported adverse effect, affecting 100% of users, followed by xerosis (94.97%) and facial erythema (66.21%). Of all adverse effects, psychiatric symptoms accounted for 25.16%; eye lesions accounted for 8.96%. In lab investigations an increase in the level of total cholesterol and serum triglycerides was observed. This study documents the adverse effect profile of isotretinoin in a large number of patients collected over a period of 4 years. Side effects were mild and well tolerated and did not necessitate stopping the treatment. However, it is important to educate patients about this potential consequence.

Superficial basal cell carcinoma treated with 70% trichloroacetic acid applied topically: a case study.

BACKGROUND: Basal cell carcinoma (BCC) is the most common form of skin cancer, affecting millions of people worldwide. The treatment concept for BCCs is the surgical one, but it is costly, as such, searching for alternative medical therapeutics is justified. AIM: To highlight the efficacy of high concentration (70%) trichloroacetic acid (TCA) as a choice therapy for low-risk BCC. METHOD AND PATIENT: Authors present, for the first time, the use of a high concentration TCA applied once a week for 2 consecutive weeks with a toothpick, on a patient with BCC on the right preauricular area. RESULTS: On examination 4 weeks later, the lesion was not clinically and dermatoscopically evidenced. CONCLUSION: High concentration TCA could be an effective and safe, non-invasive choice of therapy for low-risk BCC, easy to perform, not expensive, with good cosmetic results, especially for patients who are not likely to undergo invasive or expensive treatments.

Iatrogenic metrorrhagia after the use of itraconazole for onychomycosis.

We present first case report on itraconazole, a drug very commonly used for onychomycosis, used along with simvastatin that caused metrorrhagia. The suggested probable mechanism is the inhibition of steroidogenesis, especially estrogens that resulted in low-estrogen breakthrough bleeding. This article emphasizes the importance of drug interaction check prior the initiation of onychomycosis treatment.