Emanuele Cozzani

Serology of Lupus Erythematosus: Correlation between Immunopathological Features and Clinical Aspects

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the aberrant production of a broad and heterogenous group of autoantibodies. Even though the presence of autoantibodies in SLE has been known, for more than 60 years, still nowadays a great effort is being made to understand the pathogenetic, diagnostic, and prognostic meaning of such autoantibodies. Antibodies to ds-DNA are useful for the diagnosis of SLE, to monitor the disease activity, and correlate with renal and central nervous involvements. Anti-Sm antibodies are highly specific for SLE. Anti-nucleosome antibodies are an excellent marker for SLE and good predictors of flares in quiescent lupus. Anti-histone antibodies characterize drug-induced lupus, while anti-SSA/Ro and anti-SSB/La antibodies are associated with neonatal lupus erythematosus and photosensitivity. Anti-ribosomal P antibodies play a role in neuropsychiatric lupus, but their association with clinical manifestations is still unclear. Anti-phospholipid antibodies are associated with the anti-phospholipid syndrome, cerebral vascular disease, and neuropsychiatric lupus. Anti-C1q antibodies amplify glomerular injury, and the elevation of their titers may predict renal flares. Anti-RNP antibodies are a marker of Sharps syndrome but can be found in SLE as well. Anti-PCNA antibodies are present in 5–10% of SLE patients especially those with arthritis and hypocomplementemia.

Scleromyxedema: A multicenter study of characteristics, comorbidities, course, and therapy in 30 patients

BACKGROUND Scleromyxedema is associated with a monoclonal gammopathy and other comorbidities. Its prognostic and therapeutic features are poorly documented because most reports deal with single cases or small series. OBJECTIVE We sought to describe the characteristics of patients with scleromyxedema regarding demographics, clinical characteristics, comorbidities, therapeutic interventions, and course. METHODS We conducted a retrospective and prospective multicenter study. RESULTS We identified 30 patients with scleromyxedema (17 men and 13 women). The mean age at diagnosis was 59 years. The mean delay between disease onset and diagnosis was 9 months. Monoclonal gammopathy was detected in 27 patients. Extracutaneous manifestations were present in 19 patients including neurologic (30%), rheumatologic (23.3%), and cardiac (20%) manifestations. Two patients developed hematologic malignancies. The most common therapies included oral steroids and intravenous immunoglobulins. Although corticosteroids were ineffective, intravenous immunoglobulins (alone or in combination with other drugs) induced complete remission in 4 and partial remission in 9 patients with a mean treatment duration of 2 years. In all, 21 patients were followed up for a mean period of 33.5 months, at which time 16 patients were alive, 12 with and 4 without skin disease. Five patients died: 2 with dermatoneuro syndrome and 1 each with myeloid leukemia, Hodgkin lymphoma, and myocardial insufficiency. LIMITATIONS This is mainly a retrospective study. CONCLUSIONS Our study confirms that scleromyxedema is a chronic and unpredictable disease with severe systemic manifestations leading to a guarded prognosis. There is no specific definitive treatment. Our data support the contention that intravenous immunoglobulin is a relatively effective and safe treatment. The response is not permanent and maintenance infusions are required.

Allergic reaction to India ink in a black tattoo

An 18-year-old girl presented with intensely pruritic erythematous papules of 2 months duration, discretely scattered within and around a black tattoo on her right outer malleolus (Fig. 1). The tattoo had been made 3 months earlier by an amateur, who had used India ink (Pelikan 17 black) as a pigment. The symptoms were only partly responsive to topical corticosteroid therapy. Patch tests with the GIRDCA standard series were positive to nickel sulfate (π) and neomycin (π). The India ink brought by the patient and applied as is on the back, semi-occluded with MicroporeA tape, yielded a clear eczematous reaction (ππ) at D3 and D4. The patient denied permission for biopsy. According to the manufacturer, Pelikan 17 black India ink contains carbon black and natural resins. X-ray microanalysis of the ink was performed with a scanning electron microscope (SEM-Philips 515) attached to an energy dispersive spectrometer (EDS-EDAX 910). The inorganic component of the tattoo ink showed multiple elemental peaks, namely sodium, chlorine, barium, sulfur, potassium, silicon and traces of aluminium. No nickel was detected. As no further information was available, we could not further identify the sensitizer.

Comparative study of indirect immunofluorescence and immunoblotting for the diagnosis of autoimmune pemphigus

The diagnosis of pemphigus relies on immunopathological criteria including the detection of circulating autoantibodies to desmosomal components. In the present work we compared the usefulness of immunoblotting (IB) and indirect immunofluorescence (IIF) in the diagnosis of pemphigus using monkey oesophagus (MO) and rabbit lip (RL) as epithelial substrates. Among 54 sera from patients with well-documented pemphigus (40 pemphigus vulgaris, PV, and 14 pemphigus foliaceus, PF), 46 (85%) proved positive by IFF (46 on MO and 41 on RL) as compared with 44 (81.5%) positive by IB. IIF and IB were equally sensitive (90%) for the diagnosis of PV whereas IIF (on RL) was more sensitive (71%) than IB (57%) for the detection of PF autoantibodies. However, when the two techniques were considered in combination, the sensitivity of the detection of pemphigus autoantibodies rose to 94.5%. An IB study would therefore be warranted in the presence of an (alleged) pemphigus serum that was IIF-negative since approximately 10% of these were found to be positive. Furthermore, the pattern of IB reactivity may assist in classification, since the 130- and the 160-kDa antigens seem specifically correlated with PV and PF, respectively.

Atypical presentations of bullous pemphigoid: Clinical and immunopathological aspects

Bullous pemphigoid may occur in extremely variegated manners, misleading even experienced dermatologists. Indeed the type and/or distribution of lesions may be unusual. Furthermore, there may be an atypical demographic profile of patients, a different clinical course and a different responsiveness to therapy. Up to 20% of the cases the onset is characterized by a non-bullous phase, lasting weeks, months or in particular cases remaining the only manifestation of the disease. During this early phase lesions are generally pruritic erythematous, eczematous or urticarial; however, lesions may also resemble polycyclic, targetoid, nodular or lichenoid lesions. These atypical lesions may also coexist with typical bullae. Other atypical presentations include a vesicular eruption and an erythroderma. Manifestations in children differ from adult forms, presenting an exclusive genital involvement in 50% of cases or a preponderant involvement of the face, the palms and the soles. Rarely bullous pemphigoid is confined to certain body areas, due to particular triggering factors or to a lower disease activity. Therefore, the need to formulate universally recognized diagnostic criteria is increasingly evident, especially for atypical bullous pemphigoid. Direct immunofluorescence of perilesional skin and detection of circulating autoantibodies are mandatory in the diagnosis, especially when the clinical presentation is doubtful.

Secondary cutaneous effects of hydroxyurea: possible pathogenetic mechanisms.

We report the case of a 73‐year‐old man who had been on hydroxyurea for essential thrombocythemia since 1988. After 12 years of treatment he developed a symmetrical dermatomyositis‐like eruption together with a leg ulceration and five squamous cell carcinomas of the face. The possible pathogenetic mechanisms of these known side effects are discussed.

Scleromyxedema with an interstitial granulomatous-like pattern: A rare histologic variant mimicking granuloma annulare

Scleromyxedema is the generalized and sclerodermoid form of lichen myxedematosus. Its typical histological features include a diffuse deposition of mucin in the papillary and mid reticular dermis, an increased of collagen deposition, and a proliferation of irregularly arranged fibroblasts. We describe a 76‐year‐old man presenting with scleromyxedema associated with IgGλ monoclonal gammopathy whose biopsy showed histological features of an interstitial granulomatous‐like process consistent with interstitial granuloma annulare. The significance of these unusual granulomatous findings in the setting of scleromyxedema are unknown and have been described only once in the literature. This observation expands the spectrum of scleromyxedema and highlights the difficulty in diagnosing this disabling condition.

A molecule of about 70 kd is the immunologic marker of chronic ulcerative stomatitis

In 1990, two groups of authors1,2 independently described a particular form of chronic lichenoid stomatitis that was tentatively named chronic ulcerative stomatitis (CUS). CUS was immunologically characterized, in both direct and indirect immunofluorescence, by antinuclear antibodies that, in the two cases studied so far by immunoA molecule of about 70 kd is the immunologic marker of chronic ulcerative stomatitis

Pityriasis Rosea in Children: Clinical Features and Laboratory Investigations

Pityriasis rosea (PR) is a common, self-limiting exanthematous disease associated with a systemic reactivation of human herpesvirus 6 (HHV-6) and/or HHV-7. It usually occurs in the second or third decade of life whereas it is uncommon in patients younger than 10 years. We studied the clinical features and virological parameters of 31 children with PR, comparing them with those in adults. Our findings indicate that PR presents different characteristics between children and adults, mainly consisting of time lapse between herald patch and generalized eruption, duration of the exanthem, oropharyngeal involvement and persistence of HHV-6 and HHV-7 plasma viremia. Overall, these results suggest that, following HHV-6 and/or HHV-7 systemic active infection, the pathogenetic mechanisms involved in PR may at least partly be different in children and adults.

Anti-desmoplakin antibodies in erythema multiforme and Stevens-Johnson syndrome sera: pathogenic or epiphenomenon?

The pathophysiology of erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) is unclear. Whether autoantibodies against desmoplakin (Dp) I and II play a pathogenic role or result from an epitope spreading phenomenon is uncertain. Our aim was to characterize the keratinocyte antigens recognized in EM, TEN and SJS. Of 33 patients studied, 2 had TEN, 1 SJS, 9 EM major and 21 EM minor, according to Roujeaus criteria. All sera were studied by indirect immunofluorescence (IIF), immunoblotting and immunoprecipitation. Twenty normal sera were used as controls. 10/33 sera reacted with polypeptides of 215 and/or 250-kDa molecular mass, which co-migrate with Dp I and II as assessed by an anti-Dp I and II monoclonal antibody on IB. In IP, none of the anti-Dp I and -Dp II 10 patient sera immunoprecipitated Dp I and/or II from radiolabeled keratinocyte extracts. Two of 10 patient sera (SJS, EM minor) reacted with DpI and II when denaturated by the IB procedure. The reactivity against intracellular antigens DpI and II as denaturated proteins may result from the epidermal damage produced by aggressive autoreactive T cells, playing therefore only a secondary role in the pathogenesis of the disease.