Plaque psoriasis in patients with palmoplantar pustulosis

This study from the USA, Denmark and Germany looked at how often plaque psoriasis and palmoplantar pustulosis (PPP) occur together. Plaque psoriasis is the commonest form of psoriasis. PPP is a condition where pus-filled spots are seen on the palms and soles, often on skin that is red and scaly like psoriasis. It is not known how PPP is related to psoriasis, if at all. From insurance records in the USA and Germany, and from the Danish National Patient Register, the researchers found approximately 4000 patients diagnosed with PPP. Many of their findings varied strikingly from country to country, as noted in the commentary for this study. For instance, the prevalence of PPP ranged from 0.005% in Denmark to 0.08% in Germany. The presence of plaque psoriasis in PPP patients varied from 14.2% in the Danish patients to 36.4% in Germany and 61.3% in the USA. As regards treatment, patients with PPP and plaque psoriasis together were more likely to have been prescribed strong steroid creams, ointments or gels, especially in the USA and Denmark. More patients with both conditions together were treated with acitretin, methotrexate and biologics in the USA and Denmark, and the differences for treatment with biologics ranged widely: 18.4% of USA patients compared with 8.5% in Denmark and 2.5% in Germany. In comparison with patients with PPP alone, patients who had PPP and plaque psoriasis together were more likely to have joint disease related to psoriasis, and this was roughly the same in all three countries.     

The distribution of choline acetyltransferase- and acetylcholinesterase-like immunoreactivity in the palmar skin of patients with palmoplantar pustulosis

The distribution of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in involved skin in patients with palmoplantar pustulosis (PPP) and in normal palmar skin in healthy non-smokers and smokers has been studied by immunohistochemistry, especially in relation to the sweat gland apparatus. The sweat gland and its duct showed ChAT- and AChE-like immunoreactivity (LI) of varying intensity in all three groups and with stronger reactivity than in the epidermis. ChAT-LI was present in the coil and in the duct except in the corneal layer. Smokers and patients with PPP displayed significantly fewer ChAT+ acrosyringia than non-smokers. In the patients with PPP, the granulocytes in the pustules and in the papillary dermis displayed ChAT-LI. Western blot analysis of granulocytes from peripheral blood from healthy donors confirmed the presence of ChAT-like proteins in large amounts in neutrophils and small amounts in eosinophils. AChE-LI of varying intensity was found in all parts of the sweat gland apparatus in all three groups. The strongest AChE-LI in the acrosyringia was seen in the lowest part of the stratum corneum, where the PPP pustules are located. No significant differences in staining pattern or intensity were found between the coils, nerve fibres surrounding the coils or ducts. The number of mast cells in the papillary dermis was about four times larger in the patients with PPP than in the control subjects. AChE-LI was observed in about 25% of the mast cells in non-smoking control subjects and in patients with PPP, but only in 10% of those in the smoking control subjects. Our findings indicate that the (non-neuronal) cholinergic system may be involved in cutaneous inflammatory processes.     

Expression of nicotinic receptors in the skin of patients with palmoplantar pustulosis

BACKGROUND: A suggested role for nicotine in the pathogenesis of palmoplantar pustulosis (PPP) has been discussed. The target for the inflammation in PPP is the acrosyringium. Nicotine acts as an agonist on nicotinic acetylcholine receptors (nAChRs) and can influence a variety of cellular functions. OBJECTIVES: To study the alpha 3- and alpha 7-nAChR expression in palmar skin of patients with PPP in comparison with that in healthy smoking and non-smoking controls. METHODS: Biopsies from 20 patients with PPP, seven healthy smokers and eight healthy non-smokers were studied by immunohistochemistry with a monoclonal anti-alpha 3 and a polyclonal anti-alpha 7 antibody. RESULTS: In healthy controls both nAChR subtypes showed stronger immunoreactivity in the eccrine glands and ducts than in the epidermis. The papillary endothelium was positive for both subtypes. Epidermal alpha 3 staining was stronger and that of the coil and dermal ducts weaker in healthy smokers than in healthy non-smokers. In involved PPP skin, granulocytes displayed strong alpha 3 immunoreactivity. The normal epidermal alpha 7 staining pattern was abolished in PPP skin and was replaced by strong mesh-like surface staining, most markedly adjacent to the acrosyringium, which in controls was intensely alpha 7 positive at this level. Endothelial alpha 7 staining was stronger in PPP skin than in the controls. CONCLUSIONS: Smoking can influence nAChR expression. The altered nAChR staining pattern in PPP skin may indicate a possible role for nicotine in the pathogenesis of PPP. We hypothesize that there is an abnormal response to nicotine in patients with PPP, resulting in inflammation.     

Histocompatibility antigens in plaque psoriasis and palmoplantar pustulosis

The inheritance of susceptibility to psoriasis is thought to be multifactorial; expression of the disorder being influenced by environmental factors. Studies of histocompatibility antigens (HLA) help our understanding of the genetic inheritance of susceptibility to the disease. Early HLA studies in chronic plaque psoriasis (CPP) have shown an increased incidence of B13 and B17. More recently the antigens CW6 and DR7 have also been shown to be increased. No statistical increase has been shown in patients with persistent pustular psoriasis of the palms and soles (PPP). However there are limited data on class II antigens in this group. No previous study has compared the two groups of patients in the same population or compared clinical subsets of CPP.
Eighty-five British Caucasian patients with CPP and 45 with PPP were typed for antigens of the HLA A, B, C and DR loci. Our results confirm the increased frequencies of B13, BW57 (B17), Cw6 and DR7 in CPP patients compared with controls, and we have also found a previously unreported decrease in the frequency of BW44 (B12). In contrast the PPP patient group had increased frequencies of B8, Cw7 and DR3. HLA associations of subsets of patients related with family history, age of onset, severity of disease, the presence of arthritis and nail changes have also been assessed.     

Topical methoxsalen photochemotherapy in the treatment of palmoplantar pustulosis and psoriasis.

Topical methoxsalen photochemotherapy has been assessed in 22 patients suffering from recalcitrant palmoplantar pustulosis or psoriasis predominantly involving the hands and feet. Although 20 out of 22 patients improved and good results were obtained in exactly half of those treated, only 4 patients were classified as being "clear" or "minimally involved" at the end of 12 weeks. Two patients have shown no improvement at all. Minor local side effects were relatively common and included symptomatic erythema, blistering and local pigmentation. The histological findings in post PUVA treated skin are discussed and the pros and cons of topical photochemotherapy in this group of diseases is reviewed.     

Increased in vivo secretory activity of neutrophil granulocytes in patients with psoriasis and palmoplantar pustulosis

Summary The relationship between psoriasis and palmoplantar pustulosis (PPP) is uncertain, as is the role of the neutrophil granulocyte in these conditions. In a previous comparative study of the rate of polymorphonuclear leucocyte (PMN) phagocytosis of IGG- and IgG-C3b-coated particles, an increased uptake rate was found in both diseases. Further information on the in vivo activity of PMNs in these conditions may be obtainable by determining the level of lactoferrin (LF) in serum from such patients, since LF serves as a specific marker of the turnover and activity of the circulating pool of neutrophils. In this study on 19 patients with psoriasis and 20 patients with PPP, elevated levels of LF were found in both conditions. In contrast, the levels of lysozyme and ₂-microglobulin, which are markers of monocyte-macrophage and lymphocyte activity, respectively, were normal. This suggests the selective activation of neutrophils in these disorders. LF was significantly correlated (P<0.05 and 0.001, respectively) to the rates of phagocytosis of IgG- and IgG-C3b-coated particles, but not to the chemotaxis of isolated PMNs. There was no correlation between the severity of the disease and the levels of serum LF. The data suggest the increased in vivo activity of neutrophils in psoriasis and PPP.     

Studies on the phagocytic activity of the granulocytes in psoriasis and palmoplantar pustulosis

A kinetic method was used to determine the rates of phagocytosis of IgG-coated and C3b-IgG-coated latex particles by neutrophil granulocytes from twenty patients with psoriasis and twenty with palmoplantar pustulosis (PPP). Patients with psoriasis showed a highly increased rate of uptake of IgG-coated particles. An increased rate was also observed in patients with PPP. These results indicate enhanced Fc-receptor function. In healthy controls the uptake rate of C3b-IgG-coated particles was at least 30% higher than that of particles coated with IgG alone. In nearly half of the patients in the psoriasis and PPP groups the uptake rate failed to increase in the normal way, indicating that C3b dysfunction is common in both psoriasis and PPP. In neither group was there any relationship between the rate of phagocytosis and the clinical severity of the disease.     

Clinical and epidemiological comparison of patients affected by palmoplantar plaque psoriasis and palmoplantar pustulosis: a case series study

Summary Background In 2007 the International Psoriasis Council proposed that palmoplantar pustulosis (PPP) should be considered a separate condition from psoriasis, despite the presence of certain phenotypes common in both diseases. Objectives To describe and compare demographic and clinical characteristics among patients with PPP and palmoplantar plaque psoriasis. Methods This was a retrospective case series study from 2005 to 2010. The following data were obtained: age, sex, family history, smoking habits, nail involvement, joint involvement, disease duration, lesion morphology (plaque or pustular), histological diagnosis, comorbidities, and Physician’s Global Assessment (PGA) score for extrapalmoplantar lesions. The sample size calculation indicated that 80 patients, 40 patients for each group (palmoplantar plaque psoriasis and PPP) were needed to see clinically relevant differences between groups. Results Ninety patients were selected, 51 with palmoplantar plaque psoriasis and 39 with PPP. No statistically significant differences were registered between patients affected by PPP and palmoplantar plaque psoriasis as regards age at onset of the disease (48 vs. 44 years; P = 0·4), disease duration (6 vs. 10 years; P = 0·1), family history of psoriasis (28% vs. 33%; P = 0·7), concomitant arthritis (26% vs. 25%; P = 1·0), or smoking habits (54% vs. 41%; P = 0·2). We observed a female predominance (P = 0·01) and a lesser frequency of nail involvement (P = 0·03) in patients affected by PPP. Conclusions Our data suggest a close relationship between PPP and psoriasis. The existing data concerning epidemiology, clinical presentation, genetics, histopathology and pathogenesis do not permit a clear distinction between these two entities, which seem to coincide in many aspects. PPP appears to have a marked predilection among female smokers.     

Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis

The PSORS1 locus in the major histocompatibility complex region is the major genetic determinant for psoriasis vulgaris. Within the PSORS1 region reside at least three potential candidate genes for psoriasis susceptibility. Specific allelic variants of the genes HLA-Cw*6, HCR*WWCC, and CDSN*5 are strongly associated with psoriasis vulgaris and are in strong linkage disequilibrium with each other. We have genotyped the three psoriasis vulgaris susceptibility alleles of the PSORS1 locus in two clinical variants of psoriasis (guttate psoriasis and palmoplantar pustulosis) to study whether PSORS1 is also involved in the pathogenesis of these variants. We also asked whether these two clinical subgroups could help us to distinguish the causative gene within the high-risk PSORS1 haplotype. The association of guttate psoriasis with the three PSORS1 susceptibility alleles was similar and even stronger than seen with psoriasis vulgaris. Palmoplantar pustulosis, however, did not show association with any of the three candidate genes at this locus. Finally, no correlation with the age of onset for disease was observed. Our results show conclusively that psoriasis vulgaris and guttate psoriasis have a similar genetic basis for their association to PSORS1, whereas palmoplantar pustulosis appears to be a distinct disorder.     

Identification of Malassezia species isolated from scalp skin of patients with psoriasis and healthy subjects

The role of Malassezia species in psoriasis is still undetermined, but several reports have associated these lipophilic yeasts with the development of skin lesions in psoriasis. The aim of our study was to analyze the prevalence of Malassezia species in the scalp lesions of patients with psoriasis and assess the distribution of the species according to patient sex, age, and duration of the disease. Forty psoriatic patients with scalp involvement and the same number of clinically healthy individuals were included in the study. The samples were obtained by scraping the skin surface of the scalp of all subjects and then incubated on modified Dixon agar. The yeasts isolated were identified by their morphological and physiological properties according to Guillot et al method. M.globosa in its yeast phase was a predominant species (55%), followed by M.slooffiae (18%) and M.restricta (10%), the latter being the most common species isolated from healthy scalp skin. We found significant difference in the distribution of Malassezia species between psoriatic and healthy scalp skin and in the distribution of Malassezia species according to the severity of the scalp involvement.     

Interleukin-6 in normal skin and psoriasis.

Interleukin-6 (IL-6 or BSF-2/IFN beta 2) is a component of normal human skin. IL-6 was immunologically detected in basal keratinocytes, endothelial cells and in a number of mononucleated cells and fibroblasts in normal skin and sudoriparous ducts. In psoriasis, intense labelling of the cytoplasm in the vicinity of keratinocyte membranes was detected in all epidermal layers and other skin appendages. The fact that this interleukin acts synergistically with respect to IL-1 and Tumour Necrosis Factor (TNF) strengthens the hypothesis whereby IL-6 may contribute via its receptor action to EGF function in modulating cell hyper-proliferation in psoriasis.