Psoriasis is a skin disorder which is caused by a genetic fault. Although there is no cure for psoriasis, there are many treatment modalities to help control the disease. To evaluate treatment efficacy, the current gold standard method, PASI (Psoriasis Area and Severity Index), is used to measure psoriasis severity by evaluating the area, erythema, scaliness and thickness of the plaques. However, the determination of PASI can be tedious and subjective. In this work, we develop a computer vision method that determines one of the PASI parameters, the lesion area. The method isolates healthy and healed skin areas from lesion areas by analysing the hue and chroma information in the CIE L*a*b* colour space. Centroids of healthy skin and psoriasis in the hue-chroma space are determined from selected sample. The Euclidean distance of all pixels from each centroid is calculated. Pixels are assigned to either healthy skin or psorasis lesion classes based on the minimum Euclidean distance. The study involves patients from different ethnic origins having three different skin tones. Results obtained show that the proposed method is able to determine lesion areas with accuracy higher than 90% for 28 out of 30 cases.
Study site: Dermatology Clinic, Hospital Kuala Lumpur
Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterized by episodes of widespread sterile macroscopic pustules, with or without systemic inflammation and/or plaque psoriasis. Multiple GPP subtypes have been described, from acute GPP of von Zumbusch to milder, annular pustular psoriasis. Generalized pustular psoriasis mainly affects adults, with a female preponderance, but juvenile GPP also occurs. Flares are a hallmark of GPP and may occur de novo or be provoked by triggers, including withdrawal of systemic corticosteroids, infections, stress, pregnancy, and menstruation. Severity of flares varies widely between patients, and between flares in an individual patient. Significant flares are often accompanied by systemic symptoms, notably fever, general malaise, and extracutaneous manifestations such as arthritis, uveitis, and neutrophilic cholangitis. Common laboratory abnormalities include neutrophilia, elevated C-reactive protein levels, hypocalcemia, and abnormal liver function tests. The clinical course of GPP is highly variable; it can be a relapsing disease with recurrent flares and no pustulation between flares or a persistent disease with perpetual mild pustulation punctuated with flares of greater severity. Patients may have multiple flares per year or a flare every few years. Most flares last 2-5 weeks and approximately 50% require hospitalization. Life-threatening complications include sepsis and renal, hepatic, respiratory, and heart failure. Reported mortality rates are 2-16%.
Generalized pustular psoriasis (GPP) is a rare neutrophilic skin condition characterized by episodes of widespread eruption of sterile macroscopic pustules that can be associated with systemic inflammation. The rarity of GPP and its heterogeneous cutaneous and extracutaneous symptoms pose considerable challenges to the development and adoption of comprehensive accurate disease measures for the routine clinical assessment of disease severity and the evaluation of new treatments in clinical trials. Psoriasis disease measures remain among the most commonly used methods for evaluating patients with GPP, despite their limitations owing to a lack of assessment of pustules (a hallmark of GPP), systemic inflammation, and disease symptoms. The adaptation of psoriasis disease measures and the development of assessment tools specific for GPP severity will enable more effective and accurate monitoring of patients with GPP and enhance the clinical development of new therapies. Further clinical validation of recently developed modified assessment tools, such as the Generalized Pustular Psoriasis Physician Global Assessment and the Generalized Pustular Psoriasis Area and Severity Index, and international consensus on using quantitative tools and patient-reported outcome measures in the development of new treatments are needed to advance patient care.
Psoriasis is an incurable skin disorder affecting 2-3% of the world population. The scaliness of psoriasis is a key assessment parameter of the Psoriasis Area and Severity Index (PASI). Dermatologists typically use visual and tactile senses in PASI scaliness assessment. However, the assessment can be subjective resulting in inter- and intra-rater variability in the scores. This paper proposes an assessment method that incorporates 3D surface roughness with standard clustering techniques to objectively determine the PASI scaliness score for psoriasis lesions. A surface roughness algorithm using structured light projection has been applied to 1999 3D psoriasis lesion surfaces. The algorithm has been validated with an accuracy of 94.12%. Clustering algorithms were used to classify the surface roughness measured using the proposed assessment method for PASI scaliness scoring. The reliability of the developed PASI scaliness algorithm was high with kappa coefficients>0.84 (almost perfect agreement).
Skin colour is vital information in dermatological diagnosis as it reflects the pathological condition beneath the skin. It is commonly used to indicate the extent of diseases such as psoriasis, which is indicated by the appearance of red plaques. Although there is no cure for psoriasis, there are many treatment modalities to help control the disease. To evaluate treatment efficacy, the current gold standard method, PASI (Psoriasis Area and Severity Index), is used to determine severity of psoriasis lesion. Erythema (redness) is one parameter in PASI and this condition is assessed visually, thus leading to subjective and inconsistent results. Current methods or instruments that assess erythema have limitations, such as being able to measure erythema well for low pigmented skin (fair skin) but not for highly pigmented skin (dark skin) or vice versa. In this work, we proposed an objective assessment of psoriasis erythema for PASI scoring for different (low to highly pigmented) skin types. The colour of psoriasis lesions are initially obtained by using a chromameter giving the values L*, a*, and b* of CIELAB colour space. The L* value is used to classify skin into three categories: low, medium and highly pigmented skin. The lightness difference (DeltaL*), hue difference (Deltah(ab)), chroma (DeltaC*(ab)) between lesions and the surrounding normal skin are calculated and analysed. It is found that the erythema score of a lesion can be distinguished by their Deltah(ab) value within a particular skin type group. References of lesion with different scores are obtained from the selected lesions by two dermatologists. Results based on 38 lesions from 22 patients with various level of skin pigmentation show that PASI erythema score for different skin types i.e. low (fair skin) to highly pigmented (dark skin) skin types can be determined objectively and consistent with dermatology scoring.
Psoriasis is an immune-mediated skin disorder associated with severe systemic comorbidities. Whereas IL-36 is a key disease driver, the pathogenic role of this cytokine has mainly been investigated in skin. Thus, its effects on systemic immunity and extracutaneous disease manifestations remain poorly understood. To address this issue, we investigated the consequences of excessive IL-36 activity in circulating immune cells. We initially focused our attention on generalized pustular psoriasis (GPP), a clinical variant associated with pervasive upregulation of IL-36 signaling. By undertaking blood and neutrophil RNA sequencing, we demonstrated that affected individuals display a prominent IFN-I signature, which correlates with abnormal IL-36 activity. We then validated the association between IL-36 deregulation and IFN-I over-expression in patients with severe psoriasis vulgaris (PV). We also found that the activation of IFN-I genes was associated with extracutaneous morbidity, in both GPP and PV. Finally, we undertook mechanistic experiments, demonstrating that IL-36 acts directly on plasmacytoid dendritic cells, where it potentiates toll-like receptor (TLR)-9 activation and IFN-α production. This effect was mediated by the upregulation of PLSCR1, a phospholipid scramblase mediating endosomal TLR-9 translocation. These findings identify an IL-36/ IFN-I axis contributing to extracutaneous inflammation in psoriasis.
Psoriasis is a common skin disorder with a prevalence of 0.6 - 4.8% around the world. The most common is plaques psoriasis and it appears as red scaling plaques. Psoriasis is incurable but treatable in a long term treatment. Although PASI (Psoriasis Area and Severity Index) scoring is recognised as gold standard for psoriasis assessment, this method is still influenced by inter and intra-rater variation. An imaging and analysis system called α-PASI is developed to perform PASI scoring objectively. Percentage of lesion area to the body surface area is one of PASI parameter. In this paper, enhanced imaging methods are developed to improve the determination of body surface area (BSA) and lesion area. BSA determination method has been validated on medical mannequin. BSA accuracies obtained at four body regions are 97.80% (lower limb), 92.41% (trunk), 87.72% (upper limb), and 83.82% (head). By applying fuzzy c-means clustering algorithm, the membership functions of lesions area for PASI area scoring have been determined. Performance of scoring result has been tested with double assessment by α-PASI area algorithm on body region images from 46 patients. Kappa coefficients for α-PASI system are greater than or equal to 0.72 for all body regions (Head - 0.76, Upper limb - 0.81, Trunk - 0.85, Lower limb - 0.72). The overall kappa coefficient for the α-PASI area is 0.80 that can be categorised as substantial agreement. This shows that the α-PASI area system has a high reliability and can be used in psoriasis area assessment.
Prominent skin involvement is a defining characteristic of autoinflammatory disorders caused by abnormal IL-1 signaling. However, the pathways and cell types that drive cutaneous autoinflammatory features remain poorly understood. We sought to address this issue by investigating the pathogenesis of pustular psoriasis, a model of autoinflammatory disorders with predominant cutaneous manifestations. We specifically characterized the impact of mutations affecting AP1S3, a disease gene previously identified by our group and validated here in a newly ascertained patient resource. We first showed that AP1S3 expression is distinctively elevated in keratinocytes. Because AP1S3 encodes a protein implicated in autophagosome formation, we next investigated the effects of gene silencing on this pathway. We found that AP1S3 knockout disrupts keratinocyte autophagy, causing abnormal accumulation of p62, an adaptor protein mediating NF-κB activation. We showed that as a consequence, AP1S3-deficient cells up-regulate IL-1 signaling and overexpress IL-36α, a cytokine that is emerging as an important mediator of skin inflammation. These abnormal immune profiles were recapitulated by pharmacological inhibition of autophagy and verified in patient keratinocytes, where they were reversed by IL-36 blockade. These findings show that keratinocytes play a key role in skin autoinflammation and identify autophagy modulation of IL-36 signaling as a therapeutic target.
The identification of disease alleles underlying human autoinflammatory diseases can provide important insights into the mechanisms that maintain neutrophil homeostasis. Here, we focused our attention on generalized pustular psoriasis (GPP), a potentially life-threatening disorder presenting with cutaneous and systemic neutrophilia. Following the whole-exome sequencing of 19 unrelated affected individuals, we identified a subject harboring a homozygous splice-site mutation (c.2031-2A>C) in MPO. This encodes myeloperoxidase, an essential component of neutrophil azurophil granules. MPO screening in conditions phenotypically related to GPP uncovered further disease alleles in one subject with acral pustular psoriasis (c.2031-2A>C;c.2031-2A>C) and in two individuals with acute generalized exanthematous pustulosis (c.1705C>T;c.2031-2A>C and c.1552_1565del;c.1552_1565del). A subsequent analysis of UK Biobank data demonstrated that the c.2031-2A>C and c.1705C>T (p.Arg569Trp) disease alleles were also associated with increased neutrophil abundance in the general population (p = 5.1 × 10-6 and p = 3.6 × 10-5, respectively). The same applied to three further deleterious variants that had been genotyped in the cohort, with two alleles (c.995C>T [p.Ala332Val] and c.752T>C [p.Met251Thr]) yielding p values < 10-10. Finally, treatment of healthy neutrophils with an MPO inhibitor (4-Aminobenzoic acid hydrazide) increased cell viability and delayed apoptosis, highlighting a mechanism whereby MPO mutations affect granulocyte numbers. These findings identify MPO as a genetic determinant of pustular skin disease and neutrophil abundance. Given the recent interest in the development of MPO antagonists for the treatment of neurodegenerative disease, our results also suggest that the pro-inflammatory effects of these agents should be closely monitored.
Psoriasis is a chronic autoimmune skin disorder affecting 2-3% of the world population. It has characteristic features such as increased keratinocyte proliferation and production of inflammatory mediators. The treatment involves various strategies including topical, systemic, phototherapy and biologics. Topical therapies are preferred for mild to moderate psoriasis conditions over the systemic therapies which are ideal in severe disease conditions. The systemic therapies include immunosuppressants, biological agents and recently approved phosphodiesterase-4 (PDE4) inhibitors. There are various limitations associated with the existing therapies where the new findings in the pathogenesis of psoriasis are paving a path for newer therapeutics to target at the molecular level. Various small molecules, PDE-4 inhibitors, biologics, and immunomodulator proved efficacious including the new molecules targeting Janus kinases (JAK) inhibitors that are under investigation. Furthermore, the role of genetic and miRNAs in psoriasis is still not completely explored and may further help in improving the treatment efficacy. This review provides an insight into various emerging therapies along with currently approved treatments for psoriasis.