Mild generalised pustular psoriasis patient with a heterozygous hypomorphic MPO variant successfully treated with granulocyte and monocyte adsorption apheresis.

Pathogenic variants in MPO, which encodes the myeloperoxidase, were reported as causative genetic defects in several cases of generalised pustular psoriasis (GPP) in addition to patients with myeloperoxidase deficiency in 2020. However, which clinical subtypes of GPP patients have pathogenic variants in MPO remains largely undetermined, and elucidating this is clinically important. The present report outlines a mild case of GPP with a rare missense heterozygous variant, c.1810C>T p.(Arg604Cys), in MPO. Our structural analysis and functional assays to measure myeloperoxidase activity suggest that the present MPO substitution is a hypomorphic variant in MPO. Thus, the mild phenotype of the present GPP patient might be associated with an incomplete hypomorphic loss-of-function variant in MPO. Additionally, the severe intractable edematous pustules and erythema improved dramatically after five rounds of granulocyte and monocyte adsorption apheresis (GMA) therapy. This is the first report of GMA treatment for GPP associated with a pathogenic variant in MPO, as far as we know. Our findings suggest that GMA might be a useful and powerful tool for controlling GPP in patients with myeloperoxidase deficiency.

Intraepithelial autoimmune bullous dermatoses disease activity assessment and therapy.

Intraepithelial autoimmune blistering dermatoses are a rare group of skin disorders characterized by disruptions of inter-keratinocyte connections within the epidermis through the action of autoantibodies. The second article in this continuing medical education series presents validated disease activity scoring systems, serologic parameters of disease, treatments, and clinical trials for pemphigus and its subtypes.

A 62-year-old man with new-onset bullae.

Cutaneous blisters and/or bullae can occur in autoimmune disorders, infections, genetic diseases, and drug hypersensitivity. We present the case of a 62-year-old man with two autoimmune conditions who was admitted for antibiotic treatment of a lower extremity infection and suddenly developed a bullous rash. His physical examination was significant for tense, bullous lesions that involved his chin, palms, and inner thighs. Narrowing the differential diagnosis for patients with blistering skin lesions is imperative for timely and appropriate management.

Bullous Drug Reactions.

Bullous drug eruptions are infrequent, but because they pose a challenge both to affected patients and to treating physicians they are considered to be the most severe cutaneous adverse reactions (SCAR). It is important to recognize these conditions and to differentiate them from other clinical entities involving blister formation. There may be early signs and symptoms that indicate a severe bullous drug eruption even before blisters and erosions of the skin and mucous membranes become obvious. Once the diagnosis is suspected, appropriate diagnostic procedures and adequate management must be initiated. The latter includes identification of the potentially inducing drug, although it should be taken into account that not all cases of bullous eruptions are drug-induced. In cases with drug causality the potentially culprit agent must be withdrawn, while in cases with other aetiology the underlying condition, e.g. an infection, must be treated appropriately. In addition to best supportive care, immunomodulating therapy may be considered.

From bench to bedside: evolving therapeutic targets in autoimmune blistering disease.

Autoimmune blistering diseases comprise a group of heterogenous conditions characterized by the loss of tolerance and subsequent development of autoantibodies targeting epidermal and subepidermal adhesion proteins. Blisters and erosions form on the skin and mucous membranes leading to significant morbidity and mortality. Traditional therapies rely on systemic immunosuppression. Advancements in our understanding of the pathophysiology of pemphigus and pemphigoid have led to the development of molecules which target specific pathways involved in induction and perpetuation of disease. In this review, we outline the novel therapeutic strategies including B-cell depletion, T-regulatory cell repletion, cell signalling inhibitors and small molecular inhibitors, inhibitory monoclonal antibodies, as well as complement inhibition. We additionally review their current level of clinical evidence. We lastly review therapeutics targets gleaned from the experimental epidermolysis bullosa acquisita mouse model. These emerging treatments offer an exciting progression from basic science discoveries that have the potential to transform the treatment paradigm in autoimmune blistering diseases.

Erosive Pustular Dermatosis of the Leg Successfully Treated With an Oral Retinoid and a Bi-layered Skin Substitute

Erosive pustular dermatosis is a rare inflammatory skin disorder characterized by crusted erosions, sterile pustules, skin atrophy, and scarring alopecia. Cases of involvement of lower extremities, with or without scalp lesions, have been scarcely reported in the literature, and have been denominated Erosive Pustular Dermatosis of the Legs. The disorder usually affects elderly patients associated with chronic venous insufficiency and venous dermatitis. Topical corticosteroids and topical calcineurin inhibitors have been reported to be effective. On the other hand, several treatments have also failed to achieve appropriate results; hence we present a case of erosive pustular dermatosis of the leg, who was unresponsive to compression and antibacterial ointments, but successfully treated systemically with an oral retinoid and locally with the application of a bioengineered bi-layered skin substitute. This condition may be overlooked, which represents its low prevalence in literature. J Drugs Dermatol. 2019;18(3):301-302.

Erosive pustular dermatosis of the scalp in an adolescent with near-total hair regrowth: Case report and review of the literature.

Erosive pustular dermatosis of the scalp (EPDS) is an uncommon chronic inflammatory response to scalp trauma that usually resolves with cicatricial alopecia. It most commonly affects elderly patients with a history of actinic damage. Herein, we describe a 16-year-old girl with acrofacial dysostosis type 1 presenting after surgery with crusting purulent scalp lesions, whose clinical presentation and histopathologic findings were consistent with EPDS. A review of the literature on EPDS in children is also detailed.

Erosive pustular dermatosis of the scalp - an Australian perspective: Insights to aid clinical practice.

Erosive pustular dermatosis of the scalp has particular relevance in Australia, due to its association with actinic damage. Despite its rarity, the recalcitrant nature of erosive pustular dermatosis of the scalp dictates a protracted recovery fraught with relapse and recurrence, posing inherent challenges to successful treatment and complete recovery. In Australia, erosive pustular dermatosis of the scalp is prevalent in the elderly, who are negatively affected due to the condition. We propose a management outline to aid clinical practice, to improve the quality of life in the elderly, whilst providing insight into the current understanding and treatment of erosive pustular dermatosis of the scalp.

Erosive pustular dermatosis of the scalp: reappraisal of an underrecognized entity.

Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory dermatosis of unknown etiology. Herein, we present a review of the disease and report our own clinical and histopathological experience in eleven patients. EPDS tends to spontaneously affect bald areas of the scalp in elderly individuals. A history of previous surgery at the same site - as observed in four of our patients - is common. Coronary artery disease, cerebrovascular insult, arterial hypertension, diabetes mellitus, and severe cases of cancer were frequent comorbidities. Most patients show an undulating clinical course despite topical anti-inflammatory treatment; in some individuals, the lesions heal with scarring. Histopathology reveals scaly crusts or erosions and granulation tissue-like changes in the dermis, evolving into a scar in more advanced stages. Apart from actinic/local damage, impaired immunity and microcirculation may be predisposing factors of the disease. Similar to pyoderma gangrenosum, EPDS must be considered in the context of nonhealing wounds in the elderly after the differential diagnoses mimicking EPDS have been ruled out. Given that previous or concomitant adjacent basal cell or squamous cell carcinoma is a common finding and that infiltrative variants extending beyond the clinically visible tumor may occur, histological mapping of the surrounding skin may be advisable in doubtful cases.

Bullous Fixed Drug Eruption Caused by Doxycycline.

A 50-year-old woman presented to our dermatology clinic with pruritic lesions on her hands that had appeared 24 hours earlier. The clinical manifestations had started 24 hours after taking 100 mg of doxycycline for acute bronchitis. She had no history of allergic disease or allergic reactions to drugs. The dermatologic examination revealed multiple erythematous, purplish annular patches with overlying bullae with hemorrhagic content on both palms (Figure 1). The patient had no fever, and the rest of the physical examination did not reveal any abnormalities. Results of laboratory tests were within normal limits. A skin biopsy was performed, showing hydrophic degenerations of the basal membrane, a superficial perivascular infiltrate consisting of lymphocytes and eosinophils, and red blood cells in the dermis (Figure 2). A pharmacovigilance investigation was conducted, and doxycycline was confirmed as the agent responsible for the bullous fixed drug eruption (FDE) in our patient.

In vitro and in vivo models to investigate the pathomechanisms and novel treatments for pemphigoid diseases.

Pemphigoid diseases (PD) are a subgroup of rare acute or chronic autoimmune skin disorders characterized and caused by autoantibodies directed against distinct structural components of the dermal-epidermal junction. Binding of autoantibodies to their targets leads to the formation of blisters and erosions in patients. PDs comprise eight disorders for which the molecular target antigens have been identified. First, we review the available in vitro and ex vivo models for analysis of distinct aspects of the pathogenesis of PDs. This includes the binding of autoantibodies to skin sections, the analysis of blister formation capability and skin complement activation as well as investigation of neutrophil and keratinocyte activation. In addition to this, several animal models of PD have been developed during the last decades. These animal models have greatly contributed to our current understanding of the pathogenesis of PDs. We summarize spontaneously arising PD in animals and the induction of PD by transfer of (auto)antibodies, transfer of (auto)-antigen-specific lymphocytes and by immunization. In combined use, these models allow dissecting all aspects of PD pathogenesis, for example loss of tolerance, autoantibody production and inflammatory skin processes that lead to blister formation. Overall, we aimed to foster translational biomedical research, to deepen our understanding of PD pathogenesis and to develop novel treatments for patients suffering from these life-threatening and difficult-to-treat autoimmune diseases.

Complete remission of skin lesions in a patient with subcorneal pustular dermatosis (Sneddon-Wilkinson disease) treated with antimyeloma therapy: association with disappearance of M-protein.

Subcorneal pustular dermatosis (SPD), or Sneddon-Wilkinson disease, is a rare pustular skin disease that follows a chronic relapsing course. A well-known association exists between SPD and IgA monoclonal gammopathy of undetermined significance (MGUS), which exists in up to 40% of cases. SPD has also been observed in patients with IgA myeloma. In SPD, direct and indirect immunofluorescence studies do not reveal in vivo bound IgA to the epithelial cell surface, in contrast to IgA pemphigus, which has similar clinicopathological features. Here we describe the case of a male patient with SPD and a concurrent IgA MGUS who had been treated with dapsone for 20 years with frequent relapses. Following development of multiple myeloma, the patient was treated with intensive antimyeloma treatment consisting of high-dose melphalan with autologous stem cell transplantation. This resulted in a complete remission of the myeloma with disappearance of the M-protein. In addition, a sustained remission of SPD was achieved without further treatment. Twenty-eight months after melphalan therapy the M-protein reappeared in the serum, and 2 months later SPD reappeared with histopathologically proven skin lesions at predilection sites. Presence and absence of skin lesions was found to correlate with the presence and absence of the M-protein in the serum. This is the first report of antimyeloma therapy inducing a long-lasting remission in SPD. The findings in this patient strongly suggest a causal role for circulating IgA antibodies in the pathogenesis of SPD. Antimyeloma treatment should be considered in patients with IgA MGUS-associated SPD refractory to other therapies.

[Unintended rechallenge : Generalized bullous fixed drug eruption in two elderly women]. / Unfreiwillige Reexposition : Generalisiertes bullöses fixes Arzneiexanthem bei 2 älteren Patientinnen.

Severe bullous skin reactions like Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and generalized bullous fixed drug eruption (GBFDE) are rare, but occasionally fatal diseases which are mainly induced by drugs. We report about 2 women who both developed severe bullous skin reactions after domestic falls. Despite knowing the causative drug and having an allergy identification, both patients suffered from a secondary event after unintentional re-exposure.

Pediatric pustular psoriasis responsive to cyclosporine bridged to etanercept: A treatment approach.

Pustular psoriasis occurs rarely in children but can present with acute toxicity requiring inpatient admission. For the best approach, medical providers should have an evidence based and systematic treatment algorithm in their armamentarium. Toillustrate this point, we describe a 13-year-old girl who was admitted with generalized pustular psoriasis and who responded dramatically to "wet wrap" therapy and cyclosporine bridged to etanercept. Using this case example, we highlight the three most important considerations in any patient with new onset pustularpsoriasis: avoidance of disease complications, acute "rescue" therapy, and maintenance therapy.

Unique clinical presentations of pityriasis rosea: aphthous ulcers, vesicles and inverse distribution of lesions.

Pityriasis Rosea (PR) is a common skin disorderencountered in daily practice. Although its etiologyhas not been established, there has been widespreadresearch into possibilities. The lack of its characteristicmanifestations, specifically the herald patch andtruncal involvement, can lead to pitfalls in diagnosis.Whereas other conditions in the differential diagnosisshould be considered, PR can at times also manifest inan atypical manner. We wish to illustrate three casesof PR including those that presented with aphthousulcers, vesicles, and an inverse pattern.

Erosive pustular dermatosis of the leg: A prospective, multicentre, observational study of 36 cases.

BACKGROUND: Erosive pustular dermatosis of the leg (EPDL) is a poorly understood entity first described by Lanigan and Cotteril in 1987. Its clinical diagnosis is based on exclusion since the physiopathology is unknown. The primary objective of this investigation was to specify the clinical aspects and outcomes in a prospective study. The secondary objectives were to describe associated diseases, the circumstances of occurrence, and the laboratory tests used. PATIENTS AND METHODS: This was a prospective study that included 45 patients selected by members of the Angiology-Dermatology Group of the SFD (French Dermatology Society) at 13 centres between 01/09/2013 and 31/10/2014. There was a 180-day monitoring period. The records of 36 patients were analysed. Clinical and laboratory data were collected. RESULTS: Mean patient age was 79.6±9.9 years with a M/F sex ratio of 0.2. Among the patients, 16.7% had skin cancer and 91.7% had venous insufficiency. The proportion of patients wearing venous compression hose was constant between inclusion and D180. Lesions were bilateral (53%), affected the middle third of the leg, and were on the anterior aspect. Complete healing was achieved in 77.8% of cases with time to healing of 2.4±1.2 months, and under topical corticosteroids in 97.3% of cases. During follow-up, relapse occurred in 38.9% of cases after a mean time of 2.4±1.2 months. CONCLUSION: EPDL appears to be an idiopathic inflammatory dermatosis with a particular topographic expression. The physiopathology could be related to chronic inflammation associated with venous insufficiency and with certain trigger factors. Currently, there are few therapeutic alternatives to topical corticosteroids.

Blistering diseases in neonates.

PURPOSE OF REVIEW: Neonatal blistering diseases are rare yet potentially fatal. Therefore, it is crucial for clinicians to know its broad range of differential diagnoses. This review discusses the recent literature on the causes and the most appropriate clinical approach to neonatal blistering diseases. RECENT FINDINGS: Neonatal infections are the commonest causes for neonatal blistering. On the other hand, autoimmune blistering diseases are extremely rare with the literature limited to case reports and one systematic review only. Inherited genodermatoses are also rare, with recent developments in epidermolysis bullosa classification. SUMMARY: In conclusion, as neonatal infections are the commonest cause for blistering, any neonate with blistering should have their blister fluid investigated for infection, while an antimicrobial should be initiated early. Autoimmune blistering diseases should be considered in neonates with a maternal history of autoimmune blistering disease. Although pemphigus and bullous pemphigoid have overall good prognoses, linear IgA bullous dermatoses has a poor prognosis and requires aggressive treatment. Inherited genodermatoses should be suspected when there is a family history of genodermatoses or consanguinity. In this case, the clinician should not hesitate to seek dermatology advice, perform a skin biopsy and consider genetic testing.

The Use of Traditional Chinese Medicine in Some Dermatologic Diseases: Part II--Autoimmune Bullous Disorders and Lichen Planus.

Over the centuries, traditional Chinese medicine (TCM) and Western medicine have traveled along parallel lines with no opportunity for collaboration. In recent decades, while an interest in TCM has been growing among Western clinicians, progress has been made in the comprehension of pathogenic mechanisms of skin disorders, and the communication between Western and Eastern medicines has become more and more intensive. In this paper, the authors discuss TCM remedies used in the treatment of autoimmune bullous disorders (pemphigus and bullous pemphigoid) and lichen planus. Future studies on the active components of the TCM will certainly shed new light on the still obscure aspects of some dermatologic diseases.