Effectiveness of surgical treatment of severe macrocheilia in a patient with orofacial granulomatosis.

Orofacial granulomatosis (OFG) is the term given to a group of diseases characterized by the presence of non-necrotizing granulomatous inflammation affecting the soft tissues of the orofacial region. Treatment of OFG is often challenging and unsatisfactory. We report on a 32-year-old man with a 2-year history of oedema and swelling of the upper lip without systemic symptoms. The history, clinical features and histopathological findings led to the diagnosis of cheilitis granulomatosa (CG), a disease included in the spectrum of OFG. The patient was treated with oral diaminodiphenyl sulfone (DDS) and clofazimine without success. Oral doxycycline led to a slight improvement of the disease. Because the volume of the upper lip was twice normal size, surgical reduction was performed, followed by administration of oral doxycycline for 3 months. This therapeutic approach led to complete remission, with no recurrence after 3 years.

Mycosis fungoides: association of KIR ligands and HLA-DQB1*05 with bad prognosis of the disease.

BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. We previously reported that the prognosis of MF patients is not only related on clinical variables but it is also associated with peculiar HLA alleles. Until today, the association of HLA ligands for KIR with the prognosis of the disease has not yet been analysed. OBJECTIVE: We investigated the frequency of HLA ligands for killer cell Immunoglobulin-like receptors (KIRs) in MF patients, evaluating if the presence of particular HLA alleles that are ligands for KIR may have prognostic value. METHODS: The study includes 46 Caucasian MF patients that, between 1993 and 1997, underwent HLA genomic typing. All patients were diagnosed and followed up from 1977 to 2012 (mean follow-up of 11 years). RESULTS: MF patients have been divided into two groups (long survivors and dead patients). We noticed that the HLA-Bw6/Bw6 specificity increased among the group of seven dead patients compared to the group of 39 long survivors (71.4% vs. 41.0%, P = ns, OR = 3.59), while in the long survivors group the HLA- Bw4/Bw4 specificity increased when compared to dead patients (23.0% vs. 0%, P = ns). Moreover, we observed that six of the seven dead patients had HLA-DQB1*05; the phenotypic frequency of this HLA allele, in dead and long survivors patients, was 85.7% and 23.0% respectively (P = 0.004; OR = 20). CONCLUSION: Our observations suggest that the presence of the HLA-DQB1*05 alleles characterizes the patients with the poorest prognosis in MF. In addition, absence of the KIR-ligand epitope HLA-B Bw4 showed a trend of being more prominent in MF patients with the poorest prognosis.

Chronic localized leukocytoclastic vasculitis: clinicopathological spectrum of granuloma faciale with and without extrafacial and mucosal involvement.

Granuloma faciale (GF) is a rare cutaneous condition of unknown origin, that usually presents as one or more brown-purple papules, plaques and/or nodules, localized mostly on the face, although extrafacial lesions can also occur. Eosinophilic angiocentric fibrosis (EAF) is regarded as the mucosal counterpart of GF. Histologically, it has been described as a persistent leukocytoclastic vasculitis, with a dense polymorphous inflammatory infiltrate in the superficial and mid dermis, typically sparing the subpapillary dermis, the so called grenz zone. The presence of eosinophils is considered a characteristic feature of the disease. All the cases of GF seen at the Dermatology Unit from 2002 to 2013 were considered and reviewed, both clinically and histopathologically. Only cases with consistent clinical findings of GF, and accurate patient's history were considered. Ten cases of GF were reviewed for both histological specificity and clinico-pathological correlation. Two patients presented extrafacial lesions. One patient had involvement of nasal mucosa. Two patients suffered from associated rheumatological diseases. The most frequent histopathologic features were the presence of a grenz zone and eosinophils in the infiltrate, but also adnexal involvement was often present; vascular changes were constant, yet leukocytoclastic vasculitis could be recorded only in four cases. Fibrosis or sclerosis were always absent. Clinical pictures of the patients treated demonstrated a complete remission of the lesions, without scarring. However, a complete enduring healing was observed only in two patients, and relapse or incomplete remission of the disease was the rule. In conclusion a review of clinicopathological findings of ten patients affected by GF was made and new details of the disease presented.

Pompholyx of the hands after intravenous immunoglobulin therapy for clinically isolated syndrome: a paediatric case.

Pompholyx is a common eruption of small vesicles on the palms, soles, and/or lateral aspects of the fingers. It has a multifactorial etiology, including genetic determinants, allergy to metals, and id reaction; rarely it is a drug-related side effect. We report a paediatric case of pompholyx of the hands related to the intravenous immunoglobulin (IVIG) therapy for Clinically Isolated Syndrome (CIS). A 10-year-old boy, received an IVIG therapy (Venital, Kedrion Spa, Italy) at a dose of 400 mg/kg daily for five days. The fifth day of IVIG infusion, a symmetrical vesicular eruption appeared on the palms of the hands and on lateral aspects of the fingers. The lesions improved with application of topical steroids in few days. The mechanism of induction of pompholyx by IVIG therapy is unknown. A review of the Literature suggests the hypothesis that dyshidrotic eczematous reactions may be related not only to the type of IVIG, to the dose and the rates of infusion, but also to an allergic response to excipients and preservatives contained in the drug, probably elicited by an underlying neurological disease in some cases.

Immunogenetic factors in mycosis fungoides: can the HLA system influence the susceptibility and prognosis of the disease? Long-term follow-up study of 46 patients.

BACKGROUND: Mycosis fungoides (MF) is the most common and one of the least aggressive forms of cutaneous T-cell lymphoma. Several studies have demonstrated the influence of human leucocyte antigen (HLA) genes on the susceptibility of MF, highlighting the importance of certain alleles but, until today, no studies have evaluated the relationship between HLA alleles and the prognosis of patients with MF. OBJECTIVE: The aim of this retrospective cohort study was to evaluate the polymorphism of HLA class I and class II alleles in a group of 46 MF Caucasian patients, looking for their influence in susceptibility and prognosis of the disease. METHODS: Study population included a case-cohort sample of 46 Caucasian patients with MF that, between 1993 and 1997, underwent HLA class I and II genomic typing. All patients were diagnosed and followed up from 1977 to 2012 (mean follow-up of 11 years) and they were divided into three groups according to the evolution of the disease. RESULTS: Molecular typing at low-resolution level revealed that HLA-A*24, A*68, A*69, B*35 and DQB1*05:02 alleles were involved in susceptibility to MF. Correspondence analysis underlined that long-lasting remission was characterized by HLA-A*24 and HLA-A*25 alleles, frequent relapse by HLA-DRB1*01, DQA1*01:01, DQB1*05:01 alleles and death by HLA-A*68, HLA-B*08, HLA-B*35, HLA-C*03 alleles. CONCLUSION: This study suggests that the prognosis of MF patients is not only correlated with clinical/pathological/serological/immunological variables but it also relies on specific HLA alleles.

Tyrosine kinase inhibitors: muco-cutaneous side effects at the microscope.

In the past recent years, treatments that target receptors with kinase activity, involved in the transmission of neoplastic proliferation signals, had revolutionized cancer therapy. Imatinib mesylate has been the first of this novel family of drugs approved for the treatment of hematologic malignancies. Afterwards, other second-generation kinase inhibitors, such as dasatinib and nilotinib, have been introduced to circumvent resistance to imatinib. These target therapies have a better tolerability profile than standard chemotherapy, but their range of activity is not simply directed at tumor cells, and a wide spectrum of systemic side effects is now recognized. In particular, muco-cutaneous side effects represent the most frequent non-hematological adverse events. Due to the need of a prompt recognition of these toxicities, diagnosis is usually made on clinical grounds, and an accurate histological characterization is generally lacking. The aim of this paper was to focus on the histopathological findings of cutaneous reactions related to tyrosine kinase inhibitors use. We propose a differentiation between specific and non-specific cutaneous side effects, through an analysis of the possible etiopathogenetic mechanisms of actions of the drug, clinical aspects and major histological features. A review of the literature has been integrated by our personal experience, highlighting the importance of clinico-histological correlation, necessary to make a proper diagnosis.

Acute generalized exanthematous pustulosis: report of five cases and systematic review of clinical and histopathological findings.

Acute generalized exanthematous pustulosis (AGEP) is a rare, drug-related pustular eruption usually starting from folds with edema and erythema and with subsequent spreading. Clinically AGEP is characterized by the sudden appearance of dozen of sterile, non follicular, small pustules on erythematous and edematous skin. Mild non erosive mucosal involvement, mostly oral, may sometimes occur. Fever, neutrophilia and peripheral blood eosinophilia (in a third of patients) are present. Other skin signs such as facial edema, purpura, target-like lesions and blisters have been described but are not typical for AGEP. Diagnostic criteria for AGEP were established by an international committee of experts, the European Study of Severe Cutaneous Adverse Reactions (EuroSCAR). The most relevant histopathological feature is represented by the detection of non-follicular subcorneal and/or intracorneal spongiform pustules that are usually large, contiguous and tend to coalesce. After elimination of the causative drug, pustules usually spontaneously disappear in a few days with desquamation and the reaction fully resolves within 15 days. Internal organs are not usually involved and no systemic treatment is required. Withdrawal of the culprit drug is mandatory. Although AGEP is a self-limiting disease with a favourable prognosis, secondary infections are a not infrequent complication in patients in poor general medical conditions. The reported mortality is about 5%. The most severe cases are associated with drug rechallenge.

Histopathologic spectrum of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): a diagnosis that needs clinico-pathological correlation.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is characterized by an heterogeneous group of severe dermatologic manifestations and systemic involvement, due to several groups of medicaments. A series of 9 consecutive cases, observed from 2008 to 2013 in the Department of Dermatology, University of Pavia, is reported, all satisfying the clinical, hematological and systemic diagnostic criteria of DRESS. Clinically, 4 out of 9 patients had an urticarial and papular eruption, 2 an erythema-multiforme-like (EM-like) pattern, 2 erythroderma and 1 had an erythematous and macular reaction. Aim of the study was to describe the histopathologic features of DRESS and to trace a possible correlation between the four clinical recognized types of the syndrome and the histopathological patterns. Predominantly, a superficial perivascular lymphocytic infiltrate, extravasation of erythrocytes, and focal interface changes characterized DRESS cases. Less frequently, histopathology revealed the presence of necrotic keratinocytes; surprisingly, only in 2 cases the presence of rare dermal eosinophils was detected, even if all the patients had significant peripheral eosinophilia. A histopathological diagnosis of DRESS seems per se, according to our data, not feasible, since the main histopathological changes (interface changes, superficial perivascular dermatitis, focal spongiosis, lichenoid infiltrate, rare presence of necrotic keratinocytes) can be interpreted generically as a drug induced dermatitis. The above mentioned histopathological changes, however, when associated with clinical information on cutaneous and systemic involvement of the patient, allow the pathologist or the dermatopathologist to make a diagnosis of DRESS with a reliable margin of certainty.

Clinical, pathological and immunohistochemical effects of arsenical-ferruginous spa waters on mild-to-moderate psoriatic lesions: a randomized placebo-controlled study.

Thermalism and spa treatments are traditionally considered effective in a number of dermatologic inflammatory conditions, yet there is scarce evidence about spring water effectiveness on psoriasis in a daily setting. We enrolled 34 patients with mild-to-moderate psoriasis in a double-blind, randomized, placebo-contralaterally-controlled trial, to evaluate Levico and Vetriolo arsenical-ferruginous water effectiveness on psoriatic lesions by daily 20-minute wet packing for 12 consecutive days. Clinical, histopathologic and immunohistochemical parameters were considered. A statistically significant difference between spa water-treated lesions and placebo-treated lesions in the same patients was demonstrated for histopathologic and immunohistochemical parameters. Since iron ions have an antiproliferative effect on epithelia, and magnesium ions have an anti-inflammatory effect, Levico and Vetriolo water effectiveness on psoriasis could be addressed to their content of these ions.

Imatinib, dasatinib and nilotinib: a review of adverse cutaneous reactions with emphasis on our clinical experience.

In the last years, several tyrosine kinase inhibitors (TKIs) have been developed and approved for human cancer treatment. Imatinib mesylate was the first of this novel family of drugs that target cancer-specific molecules and signalling pathways. The appearance of imatinib resistances led to the introduction of second-generation TKIs with higher potency and selectivity, such as dasatinib and nilotinib. However, the range of activity of these agents is not simply directed at tumour cells. Patients and their clinicians are indeed frequently confronted with the cutaneous side-effects associated with the employ of these drugs, which represent the most common non-hematological adverse reactions. For this reason, a systematic dermatological survey of patients receiving these therapies is highly important, and an early and appropriate dermatological treatment is required. In this review, we analyse the clinical and pathological characteristics of the most commonly reported adverse skin events associated with first- and second-generation tyrosine kinase inhibitors, with a particular emphasis on our clinical experience.

IgA anti-epidermal transglutaminase autoantibodies: a sensible and sensitive marker for diagnosis of dermatitis herpetiformis in adult patients.

BACKGROUND: Dermatitis herpetiformis (DH) is a rare gluten-sensitive blistering itchy skin disease, strictly related to coeliac disease (CD). Direct immunofluorescence, demonstrating IgA granular deposits localized either in the dermal papillae or along the dermo-epidermal junction, is currently the gold standard for diagnosis of DH. It has been shown that DH immunocomplexes contain epidermal transglutaminase (eTG) and that sera from patients with DH contain antibodies specifically directed against eTG. OBJECTIVES: We studied the usefulness of serum eTG antibodies in discriminating between DH, CD and other gastrointestinal and dermatologic diseases. METHODS: eTG antibodies were tested in 308 adult patients' sera: 44 patients with untreated dermatitis herpetiformis (UDH), 99 patients with untreated coeliac disease (UCD), 70 dermatological controls and 95 gastrointestinal controls. RESULTS: In UDH eTG antibody levels were significantly higher than in DH patients on gluten-free diet, UCD, gastrointestinal controls and dermatological controls. In UCD eTG antibodies strongly correlated with tissue transglutaminase (tTG) antibodies, whereas in UDH no significant correlation was observed. CONCLUSION: Serum IgA eTG antibody determination can efficiently distinguish UDH from other dermatological itchy diseases and is highly sensitive to gluten-free diet.

How to make a specific diagnosis of panniculitis on clinical grounds alone: an integrated pathway of general criteria and specific findings.

A clinical approach to the vexing problem of diagnosis of panniculitis is traced in this paper, in order to obtain from the clinical findings, history and laboratory data of the patient useful, detailed and precise information, essential to address dermatologists to a specific clinical diagnosis of panniculitis. This approach is created in the same way as when a dermatologist faces any other dermatological disease, be it inflammatory or neoplastic. A common behavior in case of panniculitis is in fact just to take an adequate biopsy and wait for the pathologist report. This is indeed a limitation both for the dermatologist and above all for the pathologist, who is in tremendous need for detailed clinical information before signing his report. The most common types of panniculitides, taking into account their main clinical diagnostic criteria, will be considered. In particular, Erythema Nodosum, Panniculitides in Sarcoidosis, Pancreatic Panniculitis, Lupus Panniculitis, Erythema Induratum/Nodular Vasculitis and Weber-Christian Panniculitis/Rothman-Makai Pannicultis will be analyzed. Every chapter will consider general criteria (epidemiology, age and gender, distribution of the lesions, laboratory findings) and specific findings (characteristics of the lesions, i.e. redness, pain, tenderness, evolution, ulceration, sites of involvement) as well as comorbidities and systemic signs and symptoms. Detailed analysis of the general criteria integrated with the specific findings will allow the clinicians to reach a clinical diagnosis with a high degree of confidence.

Panniculitis in children.

This paper will give a comprehensive view of the most frequent panniculitides seen in childhood, with emphasis on the types exclusively found in infancy, and for all other types of panniculitides also found in adults. Aim of this paper is also to analyze the clinical differences between panniculitis in childhood and in adulthood, and to give reliable histopathologic criteria for a specific diagnosis. A review of the literature is here integrated by authors' personal contribution. Panniculitides in children is a heterogeneous group of diseases, as well as in adult life, characterized by inflammation of the subcutaneous fat. Only very few types of panniculitis are exclusively found in childhood, such as Sclerema neonatorum and subcutaneous fat necrosis of the newborn, while the vast majority of the other types may be found both in paediatric age and in adults. Furthermore, this paper will consider in detail panniculitis according to their frequency, such as Erythema nodosum, Lupus panniculitis, Cold panniculitis, panniculitis in Behçet disease, and poststeroid panniculitis. It will also describe rare forms of panniculitis, such as Eosinophilic panniculitis (a pathological entity debated by many authors), Subcutaneous panniculitis T-cell lymphoma, and the different forms of the so call "Lipophagic panniculitis", encompassing respectively the febrile relapsing panniculitis of Weber-Christian disease and the non-relapsing form of Rothmann-Makai disease. For each type of panniculitis considered concise information will be given about epidemiology, etiology, clinical findings, laboratory data, prognosis and therapy, while histopathologic findings will be described in detail.

Indolent systemic mastocytosis treated with narrow-band UVB phototherapy: study of five cases.

BACKGROUND: Mastocytoses represent a heterogeneous group of stem cell disorders marked by an abnormal hyperplasia and accumulation of mast cells in one or more tissues, including bone marrow, gastrointestinal tract, liver, spleen, lymph nodes and skin. Indolent systemic mastocytosis (ISM) is characterized by red-brownish and pruriginous maculopapular lesions, a bone marrow infiltration without functional impairment and an indolent clinical course with a good prognosis. In particular, the most common cutaneous symptoms are urticarial rash and mild-to-high pruritus. OBJECTIVES: This study analyses the clinical outcome of patients affected by ISM with prevalent pruriginous cutaneous symptoms and a scarce response to anti-histamines treated using narrowband ultraviolet B (NB-UVB) phototherapy. METHODS: Narrowband ultraviolet B phototherapy was administered in a UV-irradiation cabin equipped with fluorescent UVB lamps with a peak emission at 311-313 nm. The perception of pruritus severity was assessed using the Visual Analogue Scale (VAS) before starting the treatment and at each control. RESULTS: A complete remission of the cutaneous lesions and pruritus was documented in all patients after a median of 40.3 UV treatments and a median cumulative dose of 51.4 J/cm(2), with a lasting remission over a 6-month follow-up. The median VAS score at the beginning of the treatment was 86.6 (SD=6.64), whereas it decreased to 6.66 (SD=3.75) after 3 months of therapy. CONCLUSIONS: Our work provides evidence that NB-UVB phototherapy is useful for the treatment of the cutaneous symptoms and pruritus in ISM.

Prevalence, severity and clinical features of psoriasis in fingernails and toenails in adult patients: Italian experience.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease affecting 2.0-6.5% of the European population. Although the most striking clinical features of psoriasis involve the skin, other organs including nails and joints may be affected in a substantial proportion of patients. Literature reports nail involvement in 10-56% of psoriatic patients, with common physical and social impairment. However, the precise prevalence of specific clinical features of nail psoriasis is somewhat under-reported. OBJECTIVES: Our cross-sectional study aimed at describing the prevalence and the clinical features of nail involvement in adult psoriatic patients in a psoriasis referral centre in northern Italy. METHODS: A total of 178 (124 men, 54 women) consecutive adult patients (≥18 years old) with psoriasis were included. Psoriasis Area and Severity Index (PASI) and Nail Psoriasis Severity Index (NAPSI) scores were calculated for each patient. Relevant medical history was recorded. RESULTS: Nail involvement was present in 137 (99 men, 38 women) patients (76.9%). The most common nail abnormality was onycholysis, followed by crumbling, subungual hyperkeratosis, pitting and discoloration. Pitting and onycholysis were the most prevalent patterns observed in fingernails, whereas onycholysis and crumbling were the most frequent changes detected in toenails. The most frequently and severely affected nails were the fourth fingernail and the first toenail. The average PASI score was higher in individuals with nail involvement (12.0 vs. 8.7, P = 0.06). Nail changes were present in 85.7% of patients with psoriatic arthritis. CONCLUSIONS: Our study confirms that nail involvement may be overlooked in psoriasis patients. Different psoriatic patterns in the nail affect specific digits more frequently.