Long-term treatment of severe SAPHO syndrome with adalimumab: case report and a review of the literature.

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome defines an association of inflammatory cutaneous disorders with osteoarticular manifestations and represents a clinical and therapeutic challenge. We report a case of severe SAPHO syndrome with acne conglobata and a diffuse involvement of the anterior chest wall and sacroiliac joints that required treatment with isotretinoin and adalimumab, a new fully human anti-tumor necrosis factor (TNF)-α monoclonal antibody. Combination treatment determined a complete clinical remission of cutaneous and osteoarticular manifestations after 48 weeks. Despite maintenance of clinical remission, follow-up imaging studies after 24 months of adalimumab monotherapy revealed osteoarticular disease progression, with features of inflammatory osteitis. TNFα antagonists have been used as third-line therapy for SAPHO syndrome in single case reports or case series, but these lack consistent long-term follow-up. SAPHO syndrome can present an intermittent-favorable course in the majority of cases as well as a chronic-progressive course, the latter requiring aggressive combination treatment with TNFα antagonists and conventional systemic agents.

Usefulness of ultrasound imaging in detecting psoriatic arthritis of fingers and toes in patients with psoriasis.

BACKGROUND: Given that clinical evaluation may underestimate the joint damage and that early treatment can slow down psoriatic arthritis (PsA) progression, screening psoriasis patients with imaging tools that can depict early PsA changes would entail clear benefits. OBJECTIVE: To compare the ability of X-ray and ultrasound (US) examination in detecting morphological abnormalities consistent with early PsA in patients with psoriasis, using rheumatological evaluation as the gold standard for diagnosis. METHODS: Patients with chronic plaque psoriasis and no previous PsA diagnosis attending our outpatient dermatology clinic and reporting finger/toe joint and/or tendon pain underwent X-ray and US evaluation; they were subsequently referred to a rheumatologist for clinical examination and review of imaging findings. RESULTS: Abnormal US and/or X-ray findings involving at least one finger and/or toe (joints and/or tendons) were seen in 36/52 patients: 11 had one or more X-ray abnormalities, including erosion, joint space narrowing, new bone formation, periarticular soft tissue swelling, and periarticular osteoporosis; 36 had suspicious changes on US. CONCLUSION: US proved valuable in detecting joint and/or tendon abnormalities in the fingers and toes of patients with suspicious changes. The dermatologist should consider US to obtain an accurate assessment of suspicious findings.

Prevalence, characteristics and severity of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis.

BACKGROUND/AIMS: The association between NAFLD and psoriasis has never been explored in prospective epidemiological studies. The aim of this 2-phase study was to study the clinical features of NAFLD in patients with psoriasis. METHODS: Phase 1: Investigation of prevalence and characteristics of NAFLD in an unselected cohort of 142 adult Italian outpatients with psoriasis vulgaris. Phase 2: Comparison of the psoriasis cohort subgroup with NAFLD and an age- and body mass index-matched retrospective cohort of 125 non-psoriasis patients with biopsy proven NAFLD. RESULTS: Based on histories, laboratory tests, and ultrasound studies, 84 (59.2%) received clinical diagnosis of NAFLD; 30 had factors potentially associated with liver disease other than NAFLD (e.g., viral hepatitis, significant ethanol, methotrexate use); and 28 (19.7%) had normal livers. Comparison of the normal-liver and NAFLD subgroups revealed that NAFLD in psoriasis patients (Ps-NAFLD) was significantly correlated with metabolic syndrome (p<0.05); obesity (p=0.043); hypercholesterolemia (p=0.029); hypertriglyceridemia (p<0.001); AST/ALT ratio >1 (p=0.019), and psoriatic arthritis (PsA) (p=0.036). The association with PsA remained significant after logistic regression analysis (OR=3.94 [CI, 1.07-14.46]). Compared with the retrospective non-psoriatic NAFLD cohort (controls), Ps-NAFLD patients (cases) were likely to have severe NAFLD reflected by non-invasive NAFLD Fibrosis Scores and AST/ALT >1. CONCLUSIONS: NAFLD is highly prevalent among psoriasis patients, where it is closely associated with obesity (overall and abdominal), metabolic syndrome, and PsA, and more likely to cause severe liver fibrosis (compared with nonPs-NAFLD). Routine work-up for NAFLD may be warranted in patients with psoriasis, especially when potentially hepatotoxic drug therapy is being considered.

Array-based comparative genomic hybridization in early-stage mycosis fungoides: recurrent deletion of tumor suppressor genes BCL7A, SMAC/DIABLO, and RHOF.

The etiology of mycosis fungoides (MF), the most frequent form of cutaneous T cell lymphoma (CTCL), is poorly understood. No specific genetic aberration has been detected, especially in early-stage disease, possibly due to the clinical and histological heterogeneity of patient series and to the different sources of malignant cells (skin, blood, or lymph node) included in most studies. Frozen skin biopsies from 16 patients with early-stage MF were studied using array-based comparative genomic hybridization. A DNA pool from healthy donors was used as the reference. Results demonstrated recurrent loss of 19, 7p22.1-p22.3, 7q11.1-q11.23, 9q34.12, 12q24.31, and 16q22.3-q23.1, and gain of 8q22.3-q23.1 and 21q22.12. The 12q24.31 region was recurrently deleted in 7/16 patients. Real-time PCR investigation for deletion of genes BCL7A, SMAC/DIABLO, and RHOF-three tumor suppressor genes with a putative role in hematological malignancies-demonstrated that they were deleted in 9, 10, and 13 cases, respectively. The identified genomic alterations and individual genes could yield important insights into the early steps of MF pathogenesis.

Topical preparations for the treatment of psoriasis: results of a retrospective study over 15 years.

BACKGROUND: Psoriasis requires lifelong treatments that depend on the extent, clinical forms and associated conditions. OBJECTIVE: To retrospectively analyze which topical treatments were used, their efficacy, and potential advantages and disadvantages. METHODS: A total of 666 patients admitted for the first time over 15 years who were topically treated were retrospectively reviewed and subdivided using clinical forms and PASI into four groups and four subgroups for the applied treatments. For each treatment the mean PASI was calculated daily: on the first, third and sixth day. An X sample statistical analysis and Mann--Whitney U-test were performed. The hospitalization time and correlation with the response to treatment were analyzed. RESULTS: A statistically significant response was recorded for every regimen. The best combination was clobetasol propionate plus eosin on alternate days with eosin plus cade oil. The highest score was recorded for the 'en plaques' psoriasis. The average length of treatment was of 7.5 days in the best combination. No statistically significant difference among the groups was recorded with respect to the length of hospitalization and PASI. CONCLUSION: The statistically significant response for all the topical treatments analyzed and recorded in this study does not exclude a potential benefit due to hospitalization per se.

[The skin as a mirror of small intestine]. / La cute: specchio del tenue.

It is possible to observe the changes of intestinal functions, in particular absorbent, immunologic and hormonal ones, correlated to inside action of a pathogenic noxa, in the cutaneous district, thanks to clinico-dermatological manifestations. The most evident cutaneous pathologies are present in progress of inflammatory bowel diseases, however the most representative manifestations are present especially in progress of celiac disease. The importance of these associations leads to conclude that skin is the "mirror" of the small intestine, and that remembering it can be necessary for specialist and generalist in their clinical practice.

Absence of microsatellite instability and lack of evidence for subclone diversification in the pathogenesis and progression of mycosis fungoides.

Mutator phenotypes with microsatellite instability (MSI) correlated with defects in the mismatch repair system are characteristic for a subset of solid neoplasms, but are rare in non-Hodgkin lymphomas. In mismatch repair-deficient mice, however, mutator-type non-Hodgkin lymphomas are the most frequent tumors. To determine the role of MSI in mycosis fungoides, we compared the states of the eight dinucleotide microsatellite loci DXS418, DXS453, DXS556, DXS1060, D1S201, D6S260, D9S162, and D10S215 in tumor cells of 12 well-characterized patients at early- and advanced-stage diseases to matched healthy tissue. We did not find any MSI, although all but one patient had progressed to advanced-stage disease within the timeframe of the study. Concordantly, the expression of mismatch repair genes was normal. These results suggest that progressive accumulation of mutations as detected by MS analysis does not play a major role in the pathogenesis or in the progression of mycosis fungoides.

Malabsorption in psoriatic patients: cause or consequence?

OBJECTIVE: The etiopathogenesis of psoriasis is still unclear. Associations between gut and skin diseases are well known, since psoriatic patients show a high prevalence of coeliac disease. Small-bowel abnormalities can cause clinical or, more frequently, laboratory alterations that give rise to malabsorption. The aim of the study was to evaluate the prevalence of malabsorption in psoriatic patients. MATERIAL AND METHODS: Fifty-five (29 M, 26 F, mean age 51+/-8 years) psoriatic patients in the Dermatology Centre of our hospital and 65 healthy controls (36 M, 29 F, mean age 47+/-9 years) were screened for malabsorption using a D-xylose test. Psoriatic subjects who resulted positive were further investigated in order to reach a better characterization of the malabsorption using serum antigliadin, anti-endomysium and anti-transglutaminase antibodies, H2 lactulose breath test, the parasitological faecal test and colonoscopy with retrograde ileoscopy. RESULTS: Altered D-xylose absorption was found in 60% (33/55) of psoriatic patients and in 3% (2/65) of controls. Of the former, 6% had coeliac disease, 21% had bacterial overgrowth, 3% had parasitic infections and 1 patient presented eosinophilic gastroenteritis. CONCLUSIONS: Malabsorption was more prevalent among psoriatic patients than among controls. Coeliac disease, bacterial overgrowth, parasitic infestations and eosinophilic gastroenteritis could be possible causes of malabsorption in these patients. Further studies are needed to clarify the pathogenesis and possible causative associations between gut and skin diseases.

Comparison between three molecular methods for detection of blood melanoma tyrosinase mRNA. Correlation with melanoma stages and S100B, LDH, NSE biochemical markers.

BACKGROUND: The molecular monitoring of circulating tumor cells by reverse transcriptase-PCR (RT-PCR) for patients with melanoma, is still under debate. It may be affected by: a) pre-analytical variability, b) frequency of melanoma-associated gene transcripts and c) the reliability of the methods employed. Few commercial methods are available for the detection of tyrosinase mRNA in blood. OBJECTIVE: Comparison between two RT-PCR-nested methods with a third one based on real-time methodology, for detection and quantitation of tyrosinase transcripts, respectively. METHODS: Sixty-two melanoma patients with different AJCC stages and 20 healthy subjects were enrolled. All blood samples were extracted in duplicate with two different methods. Two nested-PCR methods (one commercial and one in house) plus a real time commercial kit were employed. RESULTS: The two nested PCR methods employed were overimposable, specific and sensitive, at least in the stage III, where there was a concordance between sentinel lymph nodes detection and blood tyrosinase positivity. The different extraction methods did not affect the quality of results, while the commercial real-time kit cannot be used. CONCLUSION: Tyrosinase mRNA detection may be therefore employed to monitor the melanoma patients over time in function of response to therapy.

Nail psoriasis: combined therapy with systemic cyclosporin and topical calcipotriol.

BACKGROUND: Nail psoriasis is a common problem in psoriatic patients and often it is difficult to cure. Several treatments have been proposed in the last decade using new molecules like vitamin-D analog and/or immunosoppressive drugs both systemically and locally. OBJECTIVE: Our goal was to evaluate a combination of cyclosporin and topical calcipotriol cream versus cyclosporin alone in a matched group of patients treated with cyclosporin alone. METHOD: Fifty-four patients affected by severe psoriasis and nail involvement were selected and matched for severity of nail involvement, sex, age, and cyclosporin dosage. Group A included 21 patients treated with cyclosporin alone (3.5 mg/kg/day) for three months. Group B included 33 patients treated with the same cyclosporin dosage plus, for the same time, topical application of calcipotriol cream twice a day. Evaluation for clinical improvement was the personal feeling of the patient after three months, while clinical appearance of the lesions was evaluated by the same dermatologist using digital pictures and who was blind as to the treatment of the patient. A score ranging from + to +++ was used in order to evaluate the improvement, and data were statistically evaluated with the Wilcoxon test. RESULTS: Both cyclosporin alone and a combination of cyclosporin with topical calcipotriol twice a day were useful for treating nail psoriasis after three months of therapy although the combined therapy showed a better overall result in both mild and severe nail psoriasis. Improvement of the clinical appearance of the nail lesions was seen in about 79% of patients in group B (p < or = 0.0004) versus about 47% of patients in group A (p < or = 0.15). CONCLUSIONS: In patients with severe involvement of nail psoriasis we suggest the use of a combination of topical calcipotriol twice a day with systemic treatment such as cyclosporine.

Urokinase plasminogen activator mRNA is induced by IL-1alpha and TNF-alpha in in vitro acantholysis.

The role of urokinase type plasminogen activator (uPA) has been well documented in the pathogenesis of pemphigus vulgaris (PV). Activation of plasminogen into active serine protease plasmin initiates extracellular proteolysis leading to acantholysis but the mechanisms underlying this process are not clearly understood. We have previously shown that keratinocyte derived cytokines IL-1alpha and TNF-alpha are involved in PV-induced acantholysis. In the present study we sought to examine whether keratinocyte-derived IL-1alpha and TNF-alpha are correlated with uPA induction in keratinocytes during acantholysis. Normal human keratinocytes were incubated with diluted PV serum. mRNAs for IL-1alpha, TNF-alpha and uPA were examined with RT-PCR at various time points and acantholysis was measured. IL-1alpha, TNF-alpha and uPA mRNAs were all induced in keratinocytes following PV serum stimulation; IL-1alpha/TNF-alpha mRNAs' expression was earlier than the expression of uPA mRNA. To further examine the role of IL-1alpha, TNF-alpha and uPA in acantholysis, we performed antibody blocking studies. Anti-IL-1alpha, anti-TNF-alpha and anti-uPA antibodies suppressed acantholysis by 76%, 80% and 90%, respectively. In addition, anti-IL-1alpha and anti-TNF-alpha antibodies inhibited uPA mRNA induction, whereas anti-uPA antibodies did not alter IL-1alpha/TNF-alpha mRNAs' expression. Our results confirm the role of uPA in acantholysis and suggest an involvement of IL-1alpha/TNF-alpha in uPA induction.

Achilles tendinitis in psoriasis: clinical and sonographic findings.

BACKGROUND: Involvement of the Achilles tendon is frequent in psoriatic arthritis, but it is easily missed at clinical examination. OBJECTIVE: To seek evidence of Achilles tendon abnormalities by means of sonography in psoriatic patients and to correlate sonographic findings with clinical symptoms (tendon and soft-tissue swelling, pain, and difficulty in walking). METHODS: Fifty-nine patients with plaque-type psoriasis (Psoriasis Area and Severity Index score, 3.7-34.7) and 50 healthy, aged-matched volunteers underwent clinical and sonographic evaluation of Achilles tendons and peritendinous structures. RESULTS: Eighteen (30.5%) of the 59 patients had clinical symptoms of Achilles tendinitis. Thirty-five (59.3%) of the patients had sonographic abnormalities. Of these, 13 patients had clinically symptomatic abnormalities, and 11 had psoriatic arthritis. Degenerative tendinitis was the most frequent sonographic finding (76.9%) among patients with symptomatic conditions. Five patients with symptoms did not have sonographic alterations. None of the controls had clinical or sonographic changes. CONCLUSIONS: In psoriatic patients Achilles tendon abnormalities cannot be excluded even when they are clinically absent.

Efficacy and tolerability of natural synergised pyrethrins in a new thermo labile foam formulation in topical treatment of scabies: a prospective, randomised, investigator-blinded, comparative trial vs. permethrin cream.

We compared in a prospective, randomised, investigator-blinded trial, the efficacy and tolerability of a new synergised-pyrethrins thermo-labile foam (F) formulation with permethrin 5 % cream (P) in 40 patients with scabies. Clinical evolution of scabetic lesions (Clinical grading = CG) and itching intensity (IS) were assessed, using a 5-point semi-quantitative score, at baseline, at week 2 and 4. F and P were equally effective in the clinical resolution of scabetic lesions. As compared to baseline, P reduced CG and IS from 3.4 0.7 and 3.1 0.4 to 0.2 0.6 and 1.4 1, at week 2, and to 0.0 0.0 and 0.1 0.3 at week 4, respectively (P < 0.001). F reduced CG and IS from 3.3 0.5 and 3.2 0.4 to 0.05 0.2 and 0.4 0.6 (week 2) and to 0.0 0.0 and 0.0 0.0 (week 4), respectively (P < 0.0001). As compared to P group, the IS in F group, at week 2, was significantly lower (0.4 0.6 vs. 1.4 1.1) (P < 0.0013). This foam formulation was at least as effective as permethrin 5 % cream in the treatment of scabies. In comparison with permethrin the foam induced a more rapid and complete resolution of itching.