Carlo Crosti

Autoinflammatory Skin Disorders in Inflammatory Bowel Diseases, Pyoderma Gangrenosum and Sweet’s Syndrome: a Comprehensive Review and Disease Classification Criteria

Pyoderma gangrenosum (PG) and Sweet’s syndrome (SS) are skin diseases usually presenting with recurrent ulcers and erythematous plaques, respectively. The accumulation of neutrophils in the skin, characteristic of these conditions, led to coin the term of neutrophilic dermatoses to define them. Recently, neutrophilic dermatoses have been included in the group of autoinflammatory diseases, which classically comprises genetically determined forms due to mutations of genes regulating the innate immune response. Both PG and SS are frequently associated with inflammatory bowel diseases (IBDs); however, IBD patients develop PG in 1–3xa0% of cases, whereas SS is rarer. Clinically, PG presents with deep erythematous-to-violaceous painful ulcers with well-defined borders; bullous, pustular, and vegetative variants can also occur. SS is characterized by the abrupt onset of fever, peripheral neutrophilia, tender erythematous skin lesions, and a diffuse neutrophilic dermal infiltrate. It is also known as acute febrile neutrophilic dermatosis. Treatment of PG involves a combination of wound care, topical medications, antibiotics for secondary infections, and treatment of the underlying IBD. Topical therapies include corticosteroids and the calcineurin inhibitor tacrolimus. The most frequently used systemic medications are corticosteroids and cyclosporine, in monotherapy or in combination. Dapsone, azathioprine, cyclophosphamide, methotrexate, intravenous immunoglobulins, mycophenolate mofetil, and plasmapheresis are considered second-line agents. Hyperbaric oxygen, as supportive therapy, can be added. Anti-TNF-α agents such as etanercept, infliximab, and adalimumab are used in refractory cases. SS is usually responsive to oral corticosteroids, and the above-mentioned immunosuppressants should be considered in resistant or highly relapsing cases.

Epidemiological, clinal and allergological observations on pompholyx

We have studied a group of 104 patients with pompholyx, to investigate the relationship between allergological factors and its etiopathogenesis. The following examinations were performed; blood sampling (routine tests and IgE levels), allergological tests (patch, prick, intradermal, and oral provovation tests with nickel sulphate), skin biopsy to exclude pemphigus vulgaris or bullous pemphigoid. An accurate history of familial and personal allergic diathesis was enquired for and various possible aggravating factors (season, microclimate, perspiration and emotional stress) were considered. The results were age and sex‐matched with a healthy control group (208 subjects). We found familial and personal atopic diathesis in 50% of patient wersus 11.5% of controls (p<0.001); 39 patients (37.49%) also had high levels of IgE. Nickel sulphate was the allergen with the highest positivity on patch testing: 20.19% versus 6.25% of the control group (p<0.001). The % of patients allergic to nickel reached 26%. including those (6 patients) reacting to the oral provocation test. Season (43 patients) and hyperhidrosis (38) were the aggravating factors most commonly claimed. We detected no correlation between age, sex grading of pompholyx and the allergolngical parameters investigated. Though several different allergological findings have previously been reported in dyshidrosis their role in its pathogenesis has not yet been fully explained. We think that different haptens or antigens can produce the same clinical and histological picture of pompholyx in predisposed subjects.

Small Congenital Nevi Associated with Melanoma: Case Reports and Considerations

Melanocytic nevi, both congenital and acquired, are considered to be precursors of melanomas. Data about the malignant potential of these nevi are conflicting, particularly with reference to the nevus of the smallest size. Patients with preexisting melanocytic nevi (both congenital and acquired) have risks of developing melanoma that differ from those of subjects without them. The purpose of this study was to verify the presence of melanoma in preexisting nevi both congenital (congenital nevus associated melanoma) (CNAM) and acquired (ANAM). In particular, we investigated melanomas associated with small congenital nevi (SCN). A cohort of 190 patients with primary melanomas was studied. Congenital nevi were called “small” (SCN) when their diameters were less than 1.5 cm. Epiluminescence microscopy (ELM) was performed to further improve the clinical diagnosis and to observe the more subtle changes in the preexisting nevi. Forty of the 190 cases of melanoma were associated with preexisting nevi; of these, 15 had congenital features with a CNAM largest diameter of 1.5 cm. These 15 cases were melanomas of the superficial type with a mean tumor thickness lower than that of ANAM (0.33 vs 1.50). There were no differences between the locations of CNAM and other melanomas. Male patients were significantly more affected. ELM microscopy permitted us to detect the early malignant changes in nevi and thus to improve our diagnosis. A high percentage of small congenital nevi were found to be associated with melanomas. They may be considered as melanomas precursors. Because of their large number and frequency, prophylactic removal of all SCN is not feasible. However, they should be removed as soon as possible when clinical or ELM changes are observed.

Anatomic location and histopathologic subtype of basal cell carcinomas in adults younger than 40 or 90 and older: any difference?

BACKGROUND Differences in age, site, and histopathologic subtype exist in basal cell carcinoma (BCC). OBJECTIVE To compare the distribution of BCCs in patients younger than 40 with that of those aged 90 and older according to sex, site, and subtype. METHODS & MATERIALS One hundred seventy‐five BCCs were examined. The site was classified as head and neck, trunk, or limbs and the subtype as nodular, superficial, or morpheic‐infiltrative. RESULTS Younger exhibited a lower prevalence of BCCs on the head and neck (36.0% vs 57.3%, p<.01) and a higher prevalence on the trunk (59.3% vs 31.5%, p<.01) and of superficial BCCs (43.0% vs 31.5%, p<.05) than older patients. Site was associated with subtype in younger (p<.001) and older (p=.004) patients. Superficial BCCs were mostly on the trunk (p<.001), with a higher prevalence in younger patients (86.5% vs 62.5%, p<.05). Morpheic BCCs were mostly on the head and neck (p<.001), and prevalence did not differ between age groups. Nodular BCCs were mostly on the head and neck in older patients (p=.011). Subtype was independently associated with site (p=.005) but not with age or sex. CONCLUSION A different distribution of site and subtype occurs in younger and older patients. Subtype is associated with site independent of age and sex. These findings suggest that, at least in some patients, the anatomic location of BCC may favor the development of a particular subtype. The authors have indicated no significant interest with commercial supporters.

Calcipotriol in psoriasis vulgaris: a controlled trial comparing betamethasone dipropionate + salicylic acid

Patients with psoriasis were treated with calcipotriol ointment, 50 ng/g, or betamethasone dipropionate + salicylic acid, applied twice daily, for 6 weeks. At the end of the trial patients took no treatment for a 1‐month follow‐up period. Extension of the psoriatic lesion, using a seven‐point semiquantitative scale (0, no lesion; 1, lesions involving less than 10% of the body surface; 2, 10%–30%; 3, 30%–50%; 4, 50%–70%; 5, 70%‐90%; 6, 90%–100%), and severity of the erythema, infiltration, and exfoliation, using a four‐point scale (0, no skin involvement; 3, maximal), were assessed at baseline and at the fortnightly check‐ups. The scores were then employed to calculate a PASI score.1 The dermatologist finally expressed his judgment on the efficacy of treatment, using a five‐point scale (−1, worsening; 3, healing). Similarly, patients were asked to express an opinion on the acceptability of treatment, using a five‐point scale (1, nil; 5, excellent). At baseline and at the second and sixth weeks of treatment, routine laboratory tests were carried out.

Clinical features of 36 cases of amelanotic melanomas and considerations about the relationship between histologic subtypes and diagnostic delay

Backgroundu2002 Amelanotic melanomas (AM) are a difficult diagnostic challenge for clinicians.

Contact allergy to 'caines' caused by anti-hemorrhoidal ointments.

Case Report A 38-year-old man, with no history of atopy, was started on oral clindamycin phosphate 300 mg and amoxicillin 500 mg, both 6 hourly, for bronchopneumonia. After 10 days of treatment, he developed a generalized pruriginous maculopapular eruption with lip edema and facial erythema. Clindamycin and amoxicillin were withdrawn and treatment with corticosteroids and antihistamines initiated, with a favorable outcome. 2 months later, prick tests and intradermal tests were performed with penicillin, PPL, MdM, amoxicillin, ampicillin, clindamycin phosphate and erythromycin, which were all negative at 15 min. Patch tests were performed with penicillin (10,000 IU /ml), amoxicillin (1% pet.), ampicillin (1% pet.), clindamycin phosphate (1% pet.) and erythromycin (1% pet.). The test materials were applied in rows on the back and covered by a small piece of gauze. Only clindamycin phosphate 1% pet. was positive at D3 and D4 (ππ). Patch tests with clindamycin were negative in 2 controls. Oral and i.m. challenges were made with amoxicillin and penicillin and were negative. Oral challenge with

Topical tacrolimus for the treatment of localized, idiopathic, newly diagnosed pyoderma gangrenosum

Abstract Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis which may present in a classic ulcerative form or in atypical bullous, vegetative or pustular variants. It can be associated with several disorders or be idiopathic. Although systemic immunosuppressants remain the choice therapy for most cases of PG, a local approach should be considered in localized disease. Recently, topical tacrolimus has successfully been used as an off-label drug in localized PG. In the present study, five patients with localized, idiopathic, newly diagnosed PG were treated with topical tacrolimus monotherapy. Localized PG was defined as disease involving no more than 5% of the body surface area and presenting with no more than three lesions. Cultures performed on PG lesions both before and during tacrolimus treatment were negative. In all five patients complete remission was achieved within a mean time of 6 weeks and no relapses occurred; in three cases, tacrolimus was discontinued, while the remaining two patients were applying the drug as maintenance therapy at the time of writing. Thus, we suggest that topical tacrolimus monotherapy could represent the first-line treatment for PG that fulfils the following criteria: localized disease, idiopathic form and recent onset with negative microbiological tests on PG lesions.

Clinical features and histologic pattern analysis of pigmented basal cell carcinomas in an Italian population.

To the Editor: Basal cell carcinomas (BCCs) are the most common malignant skin tuxad mors. Among these, pigmented basal cell carcinomas (PBBCs) represent a morphoxad logic expression in which the presence of a racial predilection, the difficulty of clinical differential diagnosis, the prognostic signifixad cance, the histologic subtypes involved, and the treatment success, have been rarely dexad bated (1-4) . We examined 104 Italian paxad tients with pigmented BCCs in order to evalxad uate both their prevalence and some clinixad cal parameters such as the site of the tumor, the age of presentation of the lesions, the sex ratio, the histological subtypes involved, the distribution of the pigment, and the possible recurrence rate. A total of 1217 consecutive patients with primary BCCs were studied in our clinic over a 10 year period. We analyzed the clinixad cal subtype, the site, the clinical presence of pigmentation, the sex of the affected paxad tients, and the patients age at which the tuxad mors occurred. All tumors were histologically proven to be basal cell carcinomas. They were evaluated for the presence of pigment by light microscopy of hematoxylineosin stained slides according to an arbitrary scale graded from 0 (no visible pigment) to 2 (pigment seen with the 4x objective), as prexad viously reported (1). The distribution of pigxad ment was considered peripheral when the pigment in the dermis was located laterally to tumoral nodules. Cellular distribution of the pigment refers to its presence within the tumoral cells. Stromal distribution of the pigment refers to the presence of pigment in the tumoral dermis. To compare differxad ent studies, we classified the histologic patxad tern according to a previously described Table 1. Cutaneous localization of pigmented and non-pigmented basal cell carcinomas (BCCS)

Coagulation activation in autoimmune bullous diseases

The main autoimmune blistering skin disorders are pemphigus vulgaris (PV) and bullous pemphigoid (BP). They differ in the inflammatory infiltrate, which is more intense in BP. Inflammation is known to activate coagulation in several disorders. Local and systemic activation of coagulation was evaluated in BP and PV. We studied 20 BP patients (10 active and 10 remittent), 23 PV patients (13 active and 10 remittent) and 10 healthy subjects. The coagulation markers prothrombin fragment F1+2 and D‐dimer were measured by enzyme‐immunoassays in plasma. The presence of tissue factor (TF), the main initiator of blood coagulation, was evaluated immunohistochemically in skin specimens from 10 patients with active PV, 10 patients with active BP and 10 controls. Plasma F1+2 and D‐dimer levels were significantly high in active BP (Pu2003=u20030·001), whereas in active PV the levels were normal. During remission, F1+2 and D‐dimer plasma levels were normal in both BP and PV. TF immunoreactivity was found in active BP but neither in active PV nor in normal skin. TF reactivity scores were higher in active BP than in controls or active PV (Pu2003=u20030·0001). No difference in TF scores was found between active PV and controls. BP is associated with coagulation activation, which is lacking in PV. This suggests that BP but not PV patients have an increased thrombotic risk. The observation that thrombotic complications occur more frequently in BP than in PV further supports this view.