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Author: Alexander A Navarini (86)


Jan
2018

Physicians can treat psoriasis patients with several effective treatments, however the response is individual and even the most effective therapies do sometimes not lead to a success of treatment. Currently, possible genetic markers that can predict individual therapy response are investigated. Up to now 45 genes have been identified to be associated with psoriasis [1].

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Dec
1969

Although anti-tumor necrosis factor (TNF) agents are highly effective in the treatment of psoriasis, 2-5% of treated patients develop psoriasis-like skin lesions called paradoxical psoriasis. The pathogenesis of this side effect and its distinction from classical psoriasis remain unknown. Here we show that skin lesions from patients with paradoxical psoriasis are characterized by a selective overexpression of type I interferons, dermal accumulation of plasmacytoid dendritic cells (pDC), and reduced T-cell numbers, when compared to classical psoriasis.

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Nov
2017

Pyoderma gangrenosum (PG) is a rare, neutrophilic dermatosis often associated with an underlying disease, and clinical data or larger studies are rare.
In this retrospective study, disease characteristics, clinical manifestations, and treatment response were evaluated in a Swiss cohort of PG patients.
In participating centers, 34 cases (21 females) of PG were analyzed based on clinical and histological presentation between 2002 and 2012.

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Jan
2018

Tumor necrosis factor α (TNFα) blocking drugs are in use for a wide range of autoimmune disorders. In up to 5% of patients, this class of drugs produces puzzling cutaneous side effects that are the subject of this investigation, namely psoriasiform and eczema-like skin inflammation. These side effects can occur after any time of treatment and regardless of the underlying disorders.

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Oct
2017

Mutations in Sp110 are the underlying cause of veno-occlusive disease with immunodeficiency (VODI), a combined immunodeficiency that is difficult to treat and often fatal. Because early treatment is critically important for patients with VODI, broadly usable diagnostic tools are needed to detect Sp110 protein deficiency. Several factors make establishing the diagnosis of VODI challenging: (1) Current screening strategies to identify severe combined immunodeficiency are based on measuring T cell receptor excision circles (TREC).

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Aug
2017

Repetitive skin manipulation is the key symptom in skin picking disorder (SPD) or acne excoriée des jeunes filles Brocq. The diagnostic and statistical manual of mental disorders (DSM-5) has recognized SPD as an independent disease, namely an obsessive-compulsive disorder. Thus, psychiatric treatment is indicated.

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Dec
2017

A patient withis presented together with a review of the literature of figurate erythema. Figurate lesions are emblematic for dermatology and perhaps the most picturesque efflorescences. The differential diagnosis can be broad and sometimes challenging.

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Dec
1969

Hidradenitis suppurativa (HS) is a painful, inflammatory, debilitating skin disease with a chronic intermittent course. The central pathogenetic event seems to be the occlusion of the hair follicle. HS has a 1-year prevalence of about 1%.

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Dec
1969

Subcorneal pustular dermatosis (SCPD, Sneddon-Wilkinson disease) is a rare chronic-relapsing skin disorder that typically manifests as flaccid sterile pustules without systemic symptoms. Although the accumulation of neutrophils is acknowledged to be a hallmark of SCPD, its exact pathomechanism is still not known. Several chemotactic factors have been implicated in neutrophil recruitment and invasion, including the proinflammatory cytokine TNF-α.

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Dec
1969

Acute generalized exanthematous pustulosis (AGEP) is a dramatic generalized pustular rash of severe onset, which is considered a serious cutaneous adverse reaction to drugs. However, even though the clinical features are impressive and are often accompanied by systemic inflammation, it can be controlled quickly and safely by topical steroids subsequent to interruption of the offending drug. Here, we describe the management of a case and the evolution of the pustular rash.

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Dec
1969

Due to the increasingly widespread use and side effect profile of epidermal growth factor receptor inhibitors (EGFRIs), cutaneous side effects of these drugs are frequently encountered. The EGFR is expressed on keratinocytes and fibroblasts. Inhibition of EGFR can produce a range of cutaneous adverse effects, the most frequent being a characteristic acneiform skin eruption.

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Dec
1969

Mutations in the fibroblast growth factor-receptor gene 2 () gene have been implicated in numerous diseases, including nevus comedonicus (NC) and naevoid acne that have somatic missense mutations inin the affected tissue. A patient presented in our department with unusual, innumerable large comedones throughout his back reminiscient of NC, as well as multifocal hidradenitis suppurativa and acne. Topical and systemic treatments were unsuccessful.

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Mar
2017

Solid facial edema (SFE) is a rare complication of acne vulgaris. To examine the clinical features of acne patients with solid facial edema, and to give an overview on the outcome of previous topical and systemic treatments in the cases so far published.
We report two cases from Switzerland, both young men with initially papulopustular acne resistant to topical retinoids.

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Dec
1969

Randomized controlled trials have shown the efficacy of systemic treatments in moderate-to-severe psoriasis. Clinical outcomes in psoriasis patients under real-world conditions are less well understood.
This study compared Psoriasis Area and Severity Index (PASI) and Dermatological Life Quality Index (DLQI) improvement in all psoriasis patients registered in the Swiss Dermatology Network for Targeted Therapies.

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Dec
1969

The Swiss psoriasis registry SDNTT (Swiss Dermatology Network for Targeted Therapies) records the long-term safety and effectiveness of systemic treatment regimens for psoriasis.
Patients with moderate to severe psoriasis are included in the SDNTT when treatment with a conventional systemic agent or biologic is initiated that was not previously used by the respective patient. Patients are followed over a 5-year period.

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Dec
2016

Apremilast is an oral phosphodiesterase IV inhibitor recently registered for the treatment of psoriasis and psoriatic arthritis in Switzerland and other countries. Even though it offers only moderate efficacy compared to biologics, many patients prefer drugs given by the oral route. Apremilast is frequently used in private practice, as it showed no relevant safety signals in clinical trials and often, laboratory tests are omitted completely.

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Dec
2016

Methotrexate (MTX) is an antifolic drug used in the treatment of immune-mediated and neoplastic diseases. Initiation or dosage changes in MTX therapy can cause mucositis and bone marrow suppression. Skin lesions due to acute MTX toxicity are rare, but they serve as a herald for later-onset pancytopenia.

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Dec
1969

Allergic contact dermatitis (ACD) is a common skin disease caused by a T cell-mediated immune reaction to usually innocuous allergens. ACD can have grave medical and socioeconomic consequences. ACD and irritant contact dermatitis often occur together.

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Dec
1969

A 74-year-old woman with extensive lichen planus mucosae (LPM) developed stenotic esophagitis that was refractory to intravenous glucocorticosteroids. Esophageal dilatations to 14 mm width were repeatedly performed without any lasting effect. After introducing oral apremilast, she experienced complete clinical remission within the first 4 weeks of treatment.

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Dec
1969

Psoriasis vulgaris is a common, chronic inflammatory skin disease with a prevalence of 1.5-2% in Western industrialized countries. A relevant percentage of patients suffer from moderate-to-severe psoriasis and experience a significant reduction in quality of life.

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Dec
1969

Alopecia areata is a common autoimmune disorder that targets hair follicles. Swarms of lymphocytes surround the basis of the follicles, inducing loss of pigmented terminal hair and subsequently inhibit further hair growth. Depending on the extent of involvement, alopecia areata can be associated with a dramatic reduction of quality of life.

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Jan
2016

Neutrophilic dermatoses (NDs) such as Sweet's syndrome and pyoderma gangrenosum were first described more than 50 years ago and grouped based on their clinical features combined with the typical, neutrophil-rich cutaneous inflammation. In contrast, the recently identified autoinflammatory diseases (ADs) that are also associated with neutrophil granulocyte infiltration of the skin were first characterized based on their genetic architecture. Though both the older ND and the newer AD encompass distinct conditions, they can be seen as parts of a spectrum of innate inflammation.

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Jan
2016

The skin and its blossoms--fertile soil for clinical science.

Semin Immunopathol 2016 Jan 24;38(1):1-2. Epub 2015 Nov 24.
Alexander A Navarini, Lars E French

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Jan
2016

The making of wax moulages was an exclusive and sought-after art that was primarily used for teaching, but also to document clinical and laboratory research during the first half of the 20th century. Applying the technique of moulage-making to document a case of psoriasis improvement for posterity, a moulage of the trunk of a patient with psoriasis vulgaris was taken prior to treatment with biologics - adalimumab, a TNF-α antagonist - and again 3 month after adalimumab was first given. Our modern moulage shows in the most realistic way the science-driven improvement of psoriasis achievable nowadays with biologics.

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May
2016

Sézary syndrome is a primary cutaneous T-cell lymphoma characterized by pruritic erythroderma, peripheral lymphadenopathy and the presence of malignant T cells in the blood. Unequivocal detection of malignant cells in patients with Sézary syndrome is of important diagnostic, prognostic and therapeutic value. However, no single Sézary syndrome specific cell surface marker has been identified.

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Dec
1969

Type I interferon (IFN-I) predisposes to bacterial superinfections, an important problem during viral infection or treatment with interferon-alpha (IFN-α). IFN-I-induced neutropenia is one reason for the impaired bacterial control; however there is evidence that more frequent bacterial infections during IFN-α-treatment occur independently of neutropenia.
We analyzed in a mouse model, whether Pseudomonas aeruginosa control is influenced by co-infection with the lymphocytic choriomeningitis virus (LCMV).

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Dec
2015

Caspase recruitment family member 14 (CARD14, also known as CARMA2), is a scaffold protein that mediates NF-κB signal transduction in skin keratinocytes. Gain-of-function CARD14 mutations have been documented in familial forms of psoriasis vulgaris (PV) and pityriasis rubra pilaris (PRP). More recent investigations have also implicated CARD14 in the pathogenesis of pustular psoriasis.

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Aug
2015

Data evaluating the chronological order of appearance of extraintestinal manifestations (EIMs) relative to the time of inflammatory bowel disease (IBD) diagnosis is currently lacking. We aimed to assess the type, frequency, and chronological order of appearance of EIMs in patients with IBD.
Data from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed.

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Dec
1969

Sweet's syndrome (SS) is a dermatosis with systemic symptoms characterized by tender, red nodules or papules, occasionally covered with vesicles, pustules or bullae, usually affecting the upper limbs, face and neck. SS is frequently observed in patients with leukemia or connective tissue diseases, while it is rather seldom in patients with inflammatory bowel disease. The exact pathogenesis of SS is only partially understood.

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Dec
1969

The Psoriasis Area and Severity Index (PASI) is the score of choice to grade psoriasis severity and detect clinical changes. Due to low resolution based on the calculation of the score by fixed area classes, PASI scores <10 have little value.
At 756 patient examinations, psoriasis activity was measured with both PASI and PrecisePASI.

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Feb
2015

Extramammary Paget disease (EMPD) is an insidious intraepithelial neoplasm that is difficult to control with surgery, as large resections typically are required. An effective alternative is external beam radiotherapy (EBRT), which typically results in rapid resolution of EMPD. In this study, we analyzed long-term outcomes in 7 patients who were treated with EBRT for EMPD.

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Dec
1969

Psoriatic arthritis (PsA) substantially impacts the management of psoriatic disease.
This study aimed to generate an interdisciplinary national consensus on recommendations of how PsA should be managed.
Based on a systematic literature search, an interdisciplinary expert group identified important domains and went through 3 rounds of a Delphi exercise, followed by a nominal group discussion to generate specific recommendations.

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Jun
2014

Acne vulgaris (acne) is a common inflammatory disorder of the cutaneous pilo-sebaceous unit. Here we perform a genome-wide association analysis in the United Kingdom, comparing severe cases of acne (n=1,893) with controls (n=5,132). In a second stage, we genotype putative-associated loci in a further 2,063 acne cases and 1,970 controls.

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May
2014

The PASI score, the most common outcome measure in clinical trials of psoriasis treatment, is a non-linear scale that does not allow reliable assessment of subtle variations of its components (erythema, induration, and desquamation).
Highlight treatment response patterns potentially hidden by PASI score's compounded weighted-average calculation.
Patients with moderate-to-severe psoriasis enrolled in the phase-3, 16-week, randomized CHAMPION study, and received adalimumab, methotrexate, or placebo.

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May
2014

Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.

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Apr
2013

We have reviewed the medical literature on unusually rapid Canities of body hair to assess whether the reported clinical evidence can be explained with the current hypotheses of pathogenetic mechanisms. We screened the medical literature from 1800 onward, searching for as many case reports as possible. We assessed literature in Dutch, English, French, German, Italian and Spanish and included all cases, which contained an explicit mention or description of unusually rapid graying or whitening of hair.

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Dec
1969

Morphological abnormalities of microvessels are described in psoriasis. However, there are conflicting data as to whether their function is also altered.
Our aim was to study the morphology and function of the lymphatic capillaries of psoriatic skin.

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Sep
2013

Stromal cells at epithelial surfaces contribute to innate immunity by sensing environmental danger signals and producing proinflammatory cytokines. However, the role of stromal cells in controlling local inflammation is unknown. We show that endogenous soluble IL-15 receptor α (IL-15Rα) derived from epidermal stroma, notably keratinocytes, protects against dendritic cell/IL-15-mediated, T cell-driven skin inflammation in vivo, and is relevant to human psoriasis.

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Dec
1969

Therapy-resistant lichen planus (LP) can be a challenging condition for dermatologists. There are some case reports about successful treatments with alitretinoin of cutaneous and oral, but not of esophageal LP.
We present the unique case of a patient with cutaneous, oral and esophageal LP which was refractory to classical treatment options (topical clobetasol propionate and pimecrolimus, intramuscular triamcinolone acetonide); because of systemic side effects the patient did not tolerate systemic acitretin dosed up to 25 mg daily.

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Feb
2013

Rapid activation of immune responses is necessary for antibacterial defense, but excessive immune activation can result in life-threatening septic shock. Understanding how these processes are balanced may provide novel therapeutic potential in treating inflammatory disease. Fc receptors are crucial for innate immune activation.

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