Successful treatment of acrodermatitis continua of Hallopeau coexisting with generalized pustular psoriasis with spesolimab: a case report.

Generalized pustular psoriasis (GPP) is a rare chronic inflammatory pustular dermatosis that presents as painful erythema with sterile pustules on nonacral skin. No unified standard and guideline for the treatment of GPP has been established. Several biologics have been tried for GPP, with varying success. Acrodermatitis continua of Hallopeau (ACH) is a very rare disabling variant of pustular psoriasis characterized by sterile pustules on the fingers and toes, including the nail bed. Comparatively, treating ACH is highly challenging due to its commonly therapy-resistant disease course. The pathogenic role of IL-36 signaling axis has been currently identified in GPP development. Spesolimab, the first anti-interleukin-36 receptor biologic, has been approved for treating GPP flares and shown promising results. In view of a shared pathogenesis between GPP and ACH, specolimab may be an effective treatment for ACH. Currently, there is no case and clinical trial data exist on this condition. Therefore, this case was aim to describe real-world experience of spesolimab use in ACH coexisting with GPP. We report an Asian patient with a 16-year-history of GPP and ACH with marked pustulosis on the nail bed and onychodystrophy. He received conventional systemic regimen acitretin, cyclosporine and biologics adalimumab and secukinumab, but experienced relapse for skin lesions and refractory for nail lesions. He was then treated with a single dose of spesolimab in combination with secukinumab, which resulted in skin clearance and nearly complete resolution of nail lesions over a 32-week period. Our observation suggests that spesolimab should be considered for the treatment of ACH, especially in the patients with intractable nail lesions and concomitant GPP.

A retrospective analysis of 65 patients with acrodermatitis continua of Hallopeau.

There are limited data on acrodermatitis continua of Hallopeau (ACH), particularly among Asian populations. The primary aim was to evaluate the clinical features of ACH and treatment approaches in a sizeable multicentre Asian cohort. We analysed data from adult patients diagnosed with ACH. Of 65 patients with ACH, seven patients had ACH with GPP. Females were more frequently affected in both conditions. Five (71.4%) developed GPP 5-33 years after ACH onset, while two (28.6%) developed GPP concurrently with ACH. The onset age for ACH with GPP (27.9 ± 13.6 years) was earlier than that of isolated ACH (39.8 ± 17.3 years). Metabolic comorbidities were common. ACH exhibited a chronic persistent course. Among systemic non-biologics, acitretin was the most frequently prescribed, followed by ciclosporin and methotrexate. Acitretin and ciclosporin demonstrated similar marked response rates, which surpassed that of methotrexate. Regarding biologics, a marked response was more commonly observed with interleukin-17 inhibitors than with tumour necrosis factor inhibitors. Females are predominant in both conditions. The onset age for ACH among Asian patients is earlier (late 30s) than that for Caucasian patients (late 40s). Interleukin-17 inhibitors may be more effective than tumour necrosis factor inhibitors in managing ACH.

Acquired diffuse palmoplantar erythema with keratoderma in Chinese patients with pustular psoriasis: A predictor for IL36 receptor antagonist c.115+6T>C mutation?

Several studies have suggested that mutation of the interleukin 36 receptor antagonist gene (IL36RN) is related to generalized pustular psoriasis (GPP), and the presence of IL36RN mutation may affect the clinical manifestations and treatment responses. However, genetic testing is not routinely available in clinical practice for the diagnosis of GPP. Previously, GPP patients with acrodermatitis continua of Hallopeau (ACH) were found to have a high percentage of carrying IL36RN mutation. In this study, we reported six patients with pustular psoriasis presenting as diffuse palmoplantar erythema with keratoderma among 60 patients who carried IL36RN mutation. ACH was present in five patients and five patients had acute flare of GPP. This unique presentation may serve as a predictor for IL36RN mutation in patients with pustular psoriasis, similar to ACH.

Role of zinc in health and disease.

This review provides a concise overview of the cellular and clinical aspects of the role of zinc, an essential micronutrient, in human physiology and discusses zinc-related pathological states. Zinc cannot be stored in significant amounts, so regular dietary intake is essential. ZIP4 and/or ZnT5B transport dietary zinc ions from the duodenum into the enterocyte, ZnT1 transports zinc ions from the enterocyte into the circulation, and ZnT5B (bidirectional zinc transporter) facilitates endogenous zinc secretion into the intestinal lumen. Putative promoters of zinc absorption that increase its bioavailability include amino acids released from protein digestion and citrate, whereas dietary phytates, casein and calcium can reduce zinc bioavailability. In circulation, 70% of zinc is bound to albumin, and the majority in the body is found in skeletal muscle and bone. Zinc excretion is via faeces (predominantly), urine, sweat, menstrual flow and semen. Excessive zinc intake can inhibit the absorption of copper and iron, leading to copper deficiency and anaemia, respectively. Zinc toxicity can adversely affect the lipid profile and immune system, and its treatment depends on the mode of zinc acquisition. Acquired zinc deficiency usually presents later in life alongside risk factors like malabsorption syndromes, but medications like diuretics and angiotensin-receptor blockers can also cause zinc deficiency. Inherited zinc deficiency condition acrodermatitis enteropathica, which occurs due to mutation in the SLC39A4 gene (encoding ZIP4), presents from birth. Treatment involves zinc supplementation via zinc gluconate, zinc sulphate or zinc chloride. Notably, oral zinc supplementation may decrease the absorption of drugs like ciprofloxacin, doxycycline and risedronate.

Atezolizumab-Induced Acrodermatitis and Pustular Psoriasis in a Patient with Non-Small Cell Lung Cancer: A Rare Case Report.

Introduction: Immune checkpoint inhibitors are new drugs approved for the treatment of many types of malignancies. Despite their wide use and unquestionable clinical benefits, these agents have also been associated with a unique spectrum of side effects known as immune-related adverse events. In this study, we report the first case of atezolizumab-induced pustular psoriasis and acrodermatitis. Case Presentation: A 61-year-old woman presented to our department with erythematous-desquamative and pustular lesions involving all hands and feet fingers, inguinal region, and trunk, associated to severe psoriatic onychodystrophy. She was affected by non-small-cell lung carcinoma from 12 years, and 7 months before admission, she started a treatment with atezolizumab. Conclusion: Immune checkpoint inhibitors such as atezolizumab are linked to a plethora of adverse events. Identifying and treating certain adverse skin events, particularly in cancer patients, can be a challenge, leading oncologists to discontinue immunotherapy. Our case shows how it is necessary to have a shared therapeutic algorithm in order to manage serious skin reactions in cancer patients and avoid disruption of the oncotherapy.

Anti-Interleukin-17s for successful management of pustular psoriasis.

Generalised pustular psoriasis (GPP) and acrodermatitis continua of Hallopeau (ACH) are two rare entities included in the spectrum of pustular psoriasis (PP). Due to the lack of randomised controlled clinical trials and standardized guidelines, their treatment remains a challenge for clinicians. Thus, herein we report our centre experience with the successful use of interleukin (IL)-17 inhibitors in three patients affected by PP. We also provide a brief overview of the current knowledge concerning the role of IL-17 in PP pathogenesis and of the use of IL-17 inhibitors in the treatment of PP. Based on our experience, anti-IL-17 molecules may represent a valuable therapeutical option for patients affected by different PP subtypes.

Lyme Disease: An Overview.

Lyme disease, a tick-borne multisystem disease, is caused by spirochete Borrelia burgdorferi (sensu lato). It is a common illness in temperate countries, especially the United States, but the incidence is increasing across continents due to increasing reforestation, travel and adventure tourism, increased intrusion in the vector habitat, and changing habitat of the vector. Transmission primarily occurs via bite of an infected tick (Ixodes spp.). The appearance of an erythema migrans rash following a tick bite is diagnostic of early Lyme disease even without laboratory evidence. Borrelia lymphocytoma and acrodermatitis chronica atrophicans along with multisystem involvement occur in late disseminated and chronic stages. A two-step serologic testing protocol using an enzyme-linked immunosorbent assay (ELISA) followed by confirmation of positive and equivocal results by Western immunoblot is recommended for the diagnosis. Transplacental transmission to infant occurs in the first trimester with possible congenital Lyme disease making treatment imperative during antenatal period. The treatment is most effective in the early stages of the disease, whereas rheumatological, neurological, or other late manifestations remain difficult to treat with antibiotics alone. Treatment with oral doxycycline is preferred for its additional activity against other tick-borne illnesses which may occur concurrently in 10%-15% of cases. New-generation cephalosporins and azithromycin are alternative options in patients with doxycycline contraindications. No vaccine is available and one episode of the disease will not confer life-long immunity; thus, preventive measures remain a priority. The concept of post-Lyme disease syndrome versus chronic Lyme disease remains contested for want of robust evidence favoring benefits of prolonged antibiotic therapy.

A Case of Acrodermatitis Dysmetabolica in a Child Affected by Citrullinemia Type I: When Early Diagnosis and Timely Treatment Are Not Enough.

An infant with a prenatal diagnosis of citrullinemia, who started standard treatment at birth (L-arginine; sodium benzoate and a personalized diet characterized by a low protein intake and supplementation of essential nutrients and amino acids), presented at 4 months of age with extended, progressive, and severe skin lesions consistent with acrodermatitis dysmetabolica. Guidelines for the diagnosis and management of urea cycle disorders underline that a low-protein diet places patients at risk of essential fatty acids, trace elements, and vitamin deficiency. At hospital admission, our patient had normal levels of zinc and alkaline phosphatases. The plasmatic amino acid profile revealed a severe and generalized deficiency. In particular, the serum levels of arginine, valine, and isoleucine were very low and the dermatitis did not improve until the blood levels of these amino acids increased. In our patient, skin lesions happened despite an early diagnosis of citrullinemia and timely treatment due to compliance issues as a consequence of linguistic barriers.

A novel case of limbal stem cell deficiency in a patient with acrodermatitis enteropathica.

An 18-year-old male diagnosed with acrodermatitis enteropathica (AE) since early childhood presented with worsening of dermatitis along with photophobia and watering in both eyes. Systemic evaluation by dermatology and gastroenterology specialists confirmed a diagnosis of acute exacerbation of AE, and oral zinc supplements were initiated. A best-corrected visual acuity of 20/20 was documented in both eyes. Slit-lamp examination revealed bilateral subepithelial corneal opacities in a radial fan-like pattern extending from the superior limbus toward the center. A whorled appearance of fluorescein staining and small epithelial erosions was noted in both eyes. Ocular involvements in AE such as blepharitis, cataracts, and radial corneal opacities have been reported previously. We report a new association of AE with limbal stem cell deficiency with its classical features of linear subepithelial corneal opacities with a whorling uptake of fluorescein stain and corneal erosions.

Pustular psoriasis: A distinct aetiopathogenic and clinical entity.

Pustular psoriasis is a distinct subset of psoriasis that presents with involvement of the skin in the form of sterile pustules along with systemic manifestations. Though it has been conventionally grouped under the umbrella of psoriasis, recent research has shed light on its pathogenetic mechanisms associated with the IL-36 pathway, which is distinct from conventional psoriasis. Pustular psoriasis in itself is a heterogeneous entity consisting of various subtypes, including generalised, localised, acute, and chronic forms. There is confusion regarding its current classification as entities like deficiency of IL-36 antagonist (DITRA) which are closely related to pustular psoriasis both in their pathogenetic mechanism and its clinical manifestations, are not included under pustular psoriasis. Entities like palmoplantar pustulosis, which presents with similar clinical features but is pathogenetically distinct from other forms of pustular psoriasis, are included under this condition. Management of pustular psoriasis depends upon its severity; while some of the localised variants can be managed with topical therapy alone, the generalised variants like Von Zumbusch disease and impetigo herpetiformis may need intensive care unit admission and tailor-made treatment protocols. The advent of newer biologics and better insight into the pathogenesis of pustular psoriasis has opened the way for newer therapies, including tumour necrosis factor-alpha inhibitors, interleukin-1 inhibitors, interleukin-17 inhibitors, and granulocyte monocyte apheresis. It continues to be an enigma whether pustular psoriasis is actually a variant of psoriasis or an entirely different disease entity, though we feel that it is an entirely different disease process.

Zinc: an undervalued microelement in research and treatment.

Recent years have seen a growing interest in a healthy lifestyle, particularly nutrition. An important component of a balanced diet is the microelement content. Zinc is the second most abundant trace element, after iron. It has antioxidant and immunomodulatory functions, and plays important roles in the pathogenesis of various diseases, including dermatoses. Individuals with a zinc deficiency may present with nonspecific erythematous, pustular, erosive, and bullous lesions as well as alopecia, nail dystrophy, and a variety of systemic symptoms. Any individual assessment of zinc levels should consider risk factors for deficiency, clinical symptoms, type of diet, and results of laboratory analyses. Recent research has shed light on the systemic and topical effects of zinc, indicating the value of its supplementation for many conditions.

Successful treatment of acrodermatitis continua of Hallopeau with tildrakizumab: A case report.

Acrodermatitis continua of Hallopeau is a rare, localized variant of pustular psoriasis commonly associated with join disease and severe quality of life impairment. While there are no standard treatment guidelines, therapies used for psoriasis vulgaris are commonly tried. We report a case of severe acrodermatitis continua of Hallopeau in a patient with multiple comorbidities (advanced malignancy, recurrent empyema, psoriatic arthritis) where tildrakizumab lead to a rapid resolution of skin and joint disease which was maintained 1 year later. To date, there are only four cases reporting the use of IL-23 inhibitors class in acrodermatitis continua of Hallopeau and none for tildrakizumab. However, IL-23 inhibitors should be strongly considered among the treatment of choice for acrodermatitis continua of Hallopeau, especially in patients with ongoing malignancy and/or high risk of infections.

Spotted fever group rickettsiae and Anaplasma phagocytophilum in Borrelia burgdorferi sensu lato seropositive individuals with or without Lyme disease: A retrospective analysis.

Background: The Ixodes ricinus tick is the main vector of Borrelia burgdorferi and tick-borne encephalitis virus in Switzerland. Spotted fever group Rickettsiae (SFG) and Anaplasma phagocytophilum have been detected in Swiss ticks, however, information about the extent and clinical presentation of these infections in humans is scant. Methods: Indirect fluorescent antibody tests for SFG rickettsiae and Anaplasma phagocytophilum were performed on serum samples of 121 Borrelia burgdorferi seropositive patients with and without Lyme disease and 43 negative controls. Results: Out of 121 Borrelia burgdorferi seropositive individuals, 65 (53.7%) were seropositive for IgG and 15 (12.4%) for IgM antibodies to SFG rickettsiae. IgM antibodies were detected more frequently in early-than in late-stage of Lyme disease (12 out of 51 and 2 out of 49; respectively; p â€‹= â€‹0.0078). Significantly higher IgG antibody titers against SFG rickettsiae were found in patients with late-stage compared to patients with early-stage Lyme disease (mean titer 1:261 and 1:129, respectively; p â€‹= â€‹0.038). This difference was even more pronounced in patients with acrodermatitis chronica atrophicans compared to patients with early stage of Lyme disease (mean titer 1:337 and 1:129, respectively; p â€‹= â€‹0.009).In patients presenting with fatigue, headache and myalgia, the prevalence of IgG antibodies against SFG rickettsiae was significantly higher (7 out of 11; 63.6%) than in Borrelia burgdorferi seropositive individuals without clinical illness (1 out of 10; 10%; p â€‹= â€‹0.024). IgG antibodies to Anaplasma phagocytophilum were detected in 12 out of 121 individuals (9.9%), no IgM antibodies were found. Conclusion: Infections with SFG rickettsiae and Anaplasma phagocytophilum are underdiagnosed and should be ruled out after a tick bite. Further studies are needed to elucidate the possible causative role of SFG rickettsiae for myalgia, headache and long-lasting fatigue after a tick bite and to determine the necessity for an antibiotic treatment.

Acrodermatitis Enteropathica: A Rare Case With Lifelong Implications.

Acrodermatitis enteropathica is a rare genetic disorder caused by a defect in intestinal zinc absorption, resulting in zinc deficiency and various clinical manifestations, including dermatitis, diarrhea, alopecia, and nail abnormalities. Here we present the case of a 10-year-old male child with diarrhea, and abdominal pain for several months who was diagnosed with acrodermatitis enteropathica confirmed by low serum zinc levels. The child had multiple erythematous, scaly, and crusted lesions on the hands and elbows, which resolved after starting oral zinc sulfate supplementation (10 mg/kg/day) in three divided doses. The patient's serum zinc levels normalized (1.0 µg/mL), and the skin lesions completely resolved after six months of follow-up with a regular zinc-rich diet and gradual reduction of zinc sulfate dosage to a maintenance level (2-4 mg/kg/day). This case report emphasizes the importance of timely diagnosis and treatment of acrodermatitis enteropathica to prevent the harmful consequences of zinc deficiency and highlights the need for healthcare providers to consider this disorder in children presenting with skin lesions and diarrhea, particularly those with a positive family history or consanguinity.

A rare case of chronic Gianotti-Crosti syndrome: A case report.

Gianotti-Crosti syndrome, also known as papular acrodermatitis of childhood, is a common, self-limiting dermatosis often seen in children with triggers including viral and bacterial infections along with immunizations. Lesions are generally described as asymptomatic, skin colored to erythematous papules and papulovesicles that often spontaneously resolve within weeks. Here, we will discuss Gianotti-Crosti syndrome and present a rare case of chronic Gianotti-Crosti syndrome in an otherwise healthy 3-year-old male persisting for over 20 months. From this report, we aim to better educate the dermatologic community on the extremes of the Gianotti-Crosti syndrome disease course to improve diagnosis and treatment of symptomatic patients.

Think zinc: Transient nutritional deficiency related to novel maternal SLC30A2 mutation potentially precipitated by antenatal proton pump inhibitor exposure.

A second-born breastfed infant presented with zinc deficiency. His mother had a novel heterozygous mutation in SLC30A2. A previous baby did not have zinc deficiency but the mother had taken a proton pump inhibitor (PPI) during the second pregnancy. Antenatal PPI exposure may plausibly contribute to transient infantile zinc deficiency.