Tuscan consensus on the diagnosis, treatment and follow-up of moderate-to-severe psoriasis.

BACKGROUND: Psoriasis is traditionally defined as an inflammatory chronic-relapsing disease of the skin. As widely demonstrated, this disease is also associated with multiple comorbidities: arthropathy, inflammatory bowel disease, metabolic, cardiovascular, ocular and psychological disorders. The disease also has a significant impact on patients' quality of life, whose work ability decreases considerably with clear consequences for the social costs. Therefore, if we consider that in Tuscany, more than 100,000 people out of 3,672,202 suffer from psoriasis, it is of paramount importance focusing the attention on a rational model of clinical and therapeutic management of the disease. All the leading experts in Tuscany have come together with the aim of defining unanimously accepted regional guidelines for the diagnosis, treatment, follow-up and management of psoriasis, and of providing practical guidance/protocol on diagnosis, treatment, follow-up and management of special cases of moderate-to-severe plaque psoriasis. METHODS: In a working group formed ad hoc, the main topics have been discussed and approved by plenary vote. RESULTS: Diagnosis must include a proper general health condition overview, a careful evaluation of skin and joints, the assessment and management of other comorbidities and the definition of disease severity. With regards to the therapy the best time to start a systemic treatment, the therapeutic goal, the most appropriate drug and blood tests to be performed in case of moderate severe-psoriasis have been taken into account. During follow-up, proper monitoring of systemic therapy and its management in the long term has also been suggested. Eventually, the experts have addressed the problem of how to manage the disease in special conditions, such as during surgery, pregnancy, in children and in case of infections (HBV, HCV, HIV). CONCLUSIONS: The main aim of this Consensus was to find agreement on the criteria for diagnosis, treatment and follow-up of psoriasis, shared by all the Dermatologic Therapy Units of Tuscany. A need to create an easier way for the patient to access specialized dermatology outpatient services, and to reduce the waiting list and costs related to the management of psoriasis has been stressed. Most importantly, during the Consensus all of the participants agreed on the central role of the patient, and on the need of a multidisciplinary management of the disease which requires communication among specialists and regional centers in order to build on existing experience.

Idiopathic atrophie blanche.

A 41-year-old woman presented with a 3-year history of purpuric lesions followed by superficial, painful ulcers and development of lesions on the lower legs and on the dorsa of the feet, particularly in the summer. The patient was asymptomatic during the winter months. On physical examination she had irregular, scleroatrophic, white-ivory, coalescent lesions on a livedoid basis, with purpuric and, in some lesions, pigmented borders with numerous telangiectatic capillaries. These lesions were localized on the medial sides of the lower legs and on the dorsa of the feet (Figure 1). Laboratory investigations were normal or negative, including complete blood cell count, platelets, coagulation indexes, erythrocyte sedimentation rate, serum immunoglobulins, antinuclear antibodies, anti-double-stranded DNA, anticardiolipin, antiphospholipids, antineutrophilic cytoplasmic antibodies, circulating immunocomplexes, complement fractions (C3, C4), cryoglobulins, rheumatoid factor, and Rose-Waaler reaction. The only laboratory abnormality was an elevated fibrinogen level (472 mg/dL). Doppler velocimetry excluded a chronic venous insufficiency. Thoracic x-ray and abdominal ultrasound were normal. A digital photoplethysmograph revealed functional Raynaud's phenomenon. A biopsy specimen taken from a purpuric lesion showed an atrophic epidermis with parakeratosis and focal spongiosis. An increased number of small-sized vessels were observed within a sclerotic dermis. Most of the vessels in the upper dermis were dilated and showed endothelial swelling; some were occluded due to amorphous hyaline microthrombi (Figure 2). There were fibrinoid deposits around the vessels with thickening of the vessel walls. Extravasated erythrocytes were found throughout the upper and mid-dermis. There was a sparse perivascular lymphocytic infiltrate but no vasculitis. Direct immunofluorescence showed a perivascular microgranular deposit of IgM (+), C3 (++), and fibrinogen/fibrin (+++). On the basis of clinical, serologic, histopathologic, and immunopathologic findings, a diagnosis of idiopathic atrophie blanche was made. The patient was treated with dapsone (50 mg p.o. q.d.) and pentoxifylline (400 mg p.o. t.i.d.) with pain relief and complete resolution of the ulcerations after 6 weeks of therapy.

Case study: fibrosing alopecia in a pattern distribution localized on alopecia androgenetica areas and unaffected scalp.

A 54-year-old man with a 24-year history of androgenetic alopecia was referred to the Department of Dermatological Sciences with follicular inflammatory lesions leading to scleroatrophy in the vertex region (Figure 1) of 1-year duration. These lesions appeared a year ago. There was no previous history of this condition. On examination, the patient showed confluent infiltrative follicular lesions on the frontoparietal and occipital scalp (Figure 2). Some lesions evolved into erosions that developed in ivory white scleroatrophy within weeks. These lesions were localized both in and outside of are as affected by alopecia androgenetica and were associated with mild pruritus. Histopathologic examination, performed on an early lesion of the vertex, documented a mild thinning of follicular epithelium associated with an intense lymphohistiocytic perifollicular infiltrate. The damage of the basal cell layer was limited to the follicle, while epidermis was intact. In particular, follicular keratinocytes under the isthmus showed a very intense degeneration exactly where the infiltrate was the most prominent. The damage of the hair sheath was under the isthmus and involved the lower portions of the follicles (including the hair bulbs). The inflammatory infiltrate was exclusively represented by perifollicular lymphohistiocytes. Finally, a connective fibrotic shell with numerous fibroblasts formed a sheath around the atrophic follicle (Figure 3). Results of laboratory investigations (including complete blood cell counts, basal thyroid-stimulating hormone, C-reactive protein, serum ferritin levels, B and C hepatitis markers, antinuclear antibodies, and cultural examinations) were negative.We diagnosed the patient with fibrosing alopecia in a pattern distribution.

A case of chronic herpes gestationis: persistent disease or conversion to bullous pemphigoid?

We report the case of a 38-year-old woman with herpes gestationis (HG) persistent for 26 months postpartum with typical erythematous-edematous grouped lesions associated with vesicles, blisters, and scaled crusts on most parts of her body. Despite high doses of oral prednisolone, azathioprine, and dapsone, and a trial of 5 plasmaphereses, the disease has persisted to date. Histopathologic examination of lesional skin showed subepidermal blisters, focal basal cell necrosis, and a dermal inflammatory infiltrate including many eosinophils. Direct immunofluorescence showed linear C3 staining in the basement membrane zone and the complement fixation test demonstrated circulating antibasement membrane zone antibodies at a low titer (1:80). HLA typing demonstrated an A2, A24, B35, B52, DR4,5, DR13,15, DRW52,53 phenotype. We present this case as chronic persistent HG and discuss the differential diagnosis between chronic persistent HG and HG evolving to bullous pemphigoid, together with a careful examination of similar cases reported in literature.

Subacute cutaneous lupus erythematosus in childhood.

We report a 7-year-old girl who presented with erythematous-infiltrated, figurate, well-defined lesions over sun-exposed skin and antinuclear and Ro/SSA antibodies. Lupus band test revealed granular IgM and microgranular C3 deposits at the dermoepidermal junction. Histopathologic examination of lesional skin showed orthohyperkeratosis, epidermal atrophy, widespread hydropic degeneration of the epidermal basal cell layer, and a dermal perivascular lymphohistiocytic infiltrate. The clinical, immunopathologic, and histopathologic findings were consistent with the diagnosis of annular-polycyclic variant of subacute cutaneous lupus erythematosus (SCLE). Treatment with hydroxychloroquine cleared the cutaneous lesions. We report this patient because SCLE is extremely rare in childhood, and discuss the two previous cases reported in the literature.

New insights into the pathogenesis of vitiligo: imbalance of epidermal cytokines at sites of lesions.

Vitiligo is a skin disease that is caused by selective destruction of melanocytes and is characterized by white spots. Melanocytes and keratinocytes seem to exhibit a functional close relationship, mediated at least in part by keratinocyte-derived cytokines, which seem important for survival and activity of melanocytic cells. We wanted to investigate the hypothesis that in vitiligo the expression of epidermal cytokines may be modified compared with normal skin. In 15 patients with active, non-segmental vitiligo, biopsies were obtained from lesional, perilesional and non-lesional skin; normal skin from five healthy donors was also tested. Tissue sections were tested using immunohistochemistry for the expression of keratinocyte-derived cytokines with stimulating activity, such as granulocyte-monocyte colony stimulating factor (GM-CSF), basic fibroblastic growth factor (bFGF), and stem cell factor (SCF) or with inhibiting activity, such as interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) on melanocytes. Cytokine receptors and specific melanocytic markers were also investigated. No melanocyte was identified in lesional skin by means of specific markers or c-kit receptor, whereas in perilesional, non-lesional and healthy skin, melanocytes were found in similar number. In vitiligo skin a significantly lower expression of GM-CSF, bFGF and SCF was found, and a significantly higher expression of IL-6 and TNF-alpha was detected, compared with perilesional, non-lesional and healthy skin. In conclusion, we provided evidence that a significant change of epidermal cytokines exists in vitiligo skin compared with perilesional, non-lesional and healthy skin, suggesting that the cytokine production of epidermal microenvironment may be involved in vitiligo.