Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study. / Condicionantes de acceso a nuevos medicamentos dermatológicos en España: resultados del proyecto EQUIDAD.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

[Translated article] Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Capillary malformation-arteriovenous malformation syndrome: a multicentre study.

BACKGROUND: Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a rare syndrome with characteristic skin lesions that are associated with fast-flow vascular malformations (FFVMs) in one-third of patients. Few case series have been described, and none in Spain. AIM: To identify the prevalence of dermatological parameters, FFVMs and associated features in a large series of patients with CM-AVM. METHODS: We conducted an observational study of patients with CM-AVM syndrome diagnosed in 15 Spanish hospitals over 3 years. The main clinical, radiological, genetic findings and associated diseases were analysed. RESULTS: In total, 64 patients were assessed. In 26.5% of cases, the diagnosis was incidental. In 75% of patients, there was one significantly larger macule, which we termed the 'herald patch'. FFVMs were detected in 34% of the patients, with 30% located on the skin, 7.8% in the brain and in 1.5% in the spine. There was a positive family history in 65% of the 64 patients. Genetic analysis was performed for RASA1 mutations in 57 patients, of whom 42 (73%) had a positive result. All 4 patients tested for EPHB4 mutations had a positive result. No tumour lesions were detected in the series, except for five infantile haemangiomas. CONCLUSIONS: Our data on clinical lesions, associated FFVM, family history and genetics are similar to those previously published in the literature. An extensive data analysis failed to demonstrate any statistically significant association between the presence of an FFVM and any clinical, familial or genetic parameter that could predict its onset, although a link between the presence of a herald patch on the midline face and the presence of a brain FFVM was observed. We did not detect any genotype-phenotype correlation.

Histopathological hallmarks of cutaneous lesions of capillary malformation-arteriovenous malformation syndrome.

IMPORTANCE: Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is a recently described syndrome with distinctive cutaneous lesions. Very little is known about the histopathology of these lesions. OBJECTIVE: The purpose of the study was to evaluate the histopathological characteristics of the pink macules of the CM-AVM syndrome and to investigate if these pink macules could be classified as capillary malformations or arteriovenous malformations based on their histopathological features. DESIGN-SETTINGS-PARTICIPANTS: We conducted a retrospective multicenter study involving eight hospitals in Spain. Fifteen biopsies from pink macules of the CM-AVM syndrome were analysed and compared with five biopsies of diverse capillary malformations and three stage I arteriovenous malformations. RESULTS: Pink macules' biopsies of the CM-AVM syndrome showed similar features including a high vascular density encompassing capillaries and numerous thick-walled arterioles mainly located in the superficial dermis, a predominance of elongated over round vessels, scarce or absent erythrocytes within the lumina and discrete perivascular inflammation. CMs were characterized by an increased number of capillary-type vessels mostly rounded and located in the upper dermis. AVMs were composed by highly increased numbers of vessels with a branching pattern involving the full thickness of the dermis, without erythrocytes within the lumina. Wilms tumour 1 protein was positive in the endothelial cells both in pink macules of the CM-AVM and in arteriovenous malformations. CONCLUSIONS AND RELEVANCE: Pink macules of the CM-AVM syndrome seem to be different from capillary malformations. Our results suggest that histologically and immunohistochemically they are closer to incipient arteriovenous malformations than to capillary malformations. A deepened knowledge about the nature of these skin lesions will contribute to the better understanding of capillary malformation-arteriovenous malformation syndrome, and will open the possibility of new and more specific treatments in the future.

Evidence of the high prevalence of neurological disorders in nonsyndromic X-linked recessive ichthyosis: a retrospective case series.

BACKGROUND: X-linked recessive ichthyosis (XLI) is a relatively common type of ichthyosis caused by a deficiency in the steroid sulfatase (STS) enzyme. It is the only type of ichthyosis that can be both syndromic and nonsyndromic. Typical clinical features include dark-brown scale of variable size favouring the extensor surfaces of the extremities. OBJECTIVES: To characterize clinically nonsyndromic XLI, with a particular focus on extracutaneous manifestations. METHODS: This was a multicentre retrospective review of clinical findings from a case series of patients with a clinical and genetic diagnosis of XLI. RESULTS: We identified 30 patients with XLI belonging to 25 different families carrying a deletion in the STS locus. All patients had dark scales of variable size on the extensor surfaces of the extremities. Lack of flexural involvement and pruritus were common but inconsistent findings, whereas palmoplantar hyperlinearity was absent in all but one patient. A history of orchiopexy was present in 10% and thus was more common than expected vs. the general population (3%). Neurological disorders including epilepsy (13%) and attention deficit hyperactivity disorder (ADHD; 30%) were over-represented in patients with XLI. CONCLUSIONS: This was a retrospective study with a limited number of patients. In the absence of confirmatory genetic testing and family history of the disease, dark-brown scale of the extensor surfaces and the absence of palmoplantar hyperlinearity appear to be the most reliable clinical findings supporting a diagnosis of XLI. Dermatologists should be aware of the high prevalence of ADHD and epilepsy in patients with nonsyndromic XLI.

Cutaneous involvement in an 8-year-old boy with Ras-associated autoimmune leucoproliferative disorder (RALD).

Ras-associated autoimmune leucoproliferative disorder (RALD) is a nonmalignant syndrome associated with somatic KRAS mutations. We report a patient with RALD and cutaneous lesions, the first such case reported, to our knowledge. An 8-year-old boy presented with erythematous plaques on his face and body, along with lymphadenopathies and spleen enlargement without systemic symptoms. An increased number of monocytes were found in skin biopsy, peripheral blood and bone marrow (BM). Juvenile myelomonocytic leukaemia (JMML) was suspected. Genetic study using peripheral blood showed no mutations in the KRAS, PTPN11, NRAS, CBL or BCR-ABL genes, but bone marrow analysis revealed a mutation (p-G12S/c.34 G>A) in the KRAS gene. The karyotype was normal. No KRAS mutations were found using molecular analysis of saliva. The diagnosis of RALD was proposed. The differential diagnosis between RALD and JMML is challenging because there are no established criteria to differentiate between them. The clinical course of RALD is uncertain, so long-term follow-up is recommended.

Changing perspectives in atopic dermatitis.

Atopic dermatitis (AD) is a multifaceted disease that involves a complex interplay between the skin and the immune system. The course of the disease depends strongly on the genetic background of the patient and on yet poorly-defined environmental factors. Changes in lifestyle could be behind the dramatic rise in the prevalence of AD across continents; including hygienic conditions, food, social habits, skin microbiome or exposure to a number of allergens. Although AD typically develops in childhood and disappears after a few years, in a relatively large number of patients it continues into adulthood. Adult AD can also appear de novo but it is often underdiagnosed and its treatment can be challenging. New, highly effective drugs are being developed to manage moderate and severe forms of the disease in adults. In this review, we highlight the most recent developments in diagnostic tools, current insights into the mechanistic basis of this disease, and therapeutic innovations.

Amelanotic naevoid melanoma in a 16-month-old albino infant.

Melanoma in individuals with oculocutaneous albinism has been reported in the literature to be rare compared with the more common occurrence of squamous cell carcinoma and basal cell carcinoma. We present a singular case of amelanotic naevoid melanoma arising from a small congenital naevus in a 16-month old albino boy, the youngest reported to date.

Infantile hemangiomas with minimal or arrested growth associated with soft tissue hypertrophy: a case series of 10 patients.

BACKGROUND: Infantile hemangiomas with minimal or arrested growth (IH-MAGs) are characterized by a proliferative component of <25% of its surface area. The co-occurrence of IH-MAGs and soft tissue anomalies is rare, and case series of this association are lacking. OBJECTIVE: We present 10 cases of IH-MAGs associated with soft tissue hypertrophy and describe their clinical features. METHODS: We reviewed all infantile hemangiomas with minimal or arrested growth seen between 2009 and 2016 in the dermatology clinic department at Hospital Santa Creu i Sant Pau, Barcelona. To collect more patients, we also requested cases from the Hemangioma Investigator Group and members of the Spanish Society of Vascular Anomalies. RESULTS: Ten patients had IH-MAGs associated with soft tissue hypertrophy; seven involving the arm and three involving the leg. All displayed a segmental pattern, a doughy and puffy texture and prominent surface veins. No significant asymmetries in limbs and no other visceral anomalies were observed at follow-up (range 15 months to 7 years). One patient reported coldness in the limb with infantile hemangioma, but RMI-angiography did not disclose a vascular malformation underneath the lesion. Ulceration was observed in three patients. The proliferative component in all IH-MAGs had faded at 1-year follow-up, while soft tissue hypertrophy and prominent vessels remained unchanged. CONCLUSIONS: In this first case series of IH-MAGS associated with soft tissue hypertrophy, soft tissue hypertrophy was not progressive and remained unchanged over time, unlike the proliferative component of classic infantile hemangioma. The origin of the prominent vessels and the higher ulceration risk are unknown; however, these findings are probably related to a minor disruption of local vessels not detected in imaging tests.