Cutis marmorata telangiectatica congenita and chronic autoimmune urticaria in a young man.

A 20-year-old man with mental impairment, was referred to us for evaluation of recurring idiopathic urticaria episodes, characterized by a diffuse spreading of wheals and severe itching lacking response to traditional antihistamines. Upon physical examination, he showed a persistent, generalized, reticular, red-bluish vascular skin pattern in association with diffuse arborizing telangiectasias. Such lesions were present from an early age. Laboratory and instrumental tests, performed in order to exclude any condition associated with livedo did not evidence pathological results. He was found to be positive for antinuclear autoantibodies (ANA; 1:640). Histopathologically, numerous dilated capillary vessels associated with sparse extravasated erythrocytes were observed in the upper dermis. We performed an autologous serum skin test (ASST), which resulted in a positive, suggesting an autoimmune basis of the condition. On the basis of clinical and histopathological findings, and in the absence of other clinical and laboratory data suggesting other neoplastic, immunological or systemic diseases, the diagnosis of cutis marmorata telangiectatica congenita (CMTC) associated with chronic autoimmune urticaria (CAIU) was made. CMTC is a rare congenital vascular disorder, consisting in an anomalous, persistent, red-bluish marbling of the skin, that can be associated with a wide spectrum of cutaneous and extracutaneous anomalies. In our case, neither physical examination nor instrumental investigation demonstrated any of these anomalies, with the exception of cognitive impairment. We report this case because of the rarity of a diagnosis of CMTC in an adult patient, because this condition has almost always previously been diagnosed in infancy, or it comes to observation because of the presence of associated disorders, as in our case for chronic urticaria.

Case study: periodic follow-up is necessary in morphea profunda to identify systemic evolution.

The term "morphea" includes a wide spectrum of clinical entities, varying from localized plaques of only cosmetic importance to deep lesions resulting in considerable morbidity for the patient. In fact, although survival rates are no different from that of the general population, localized scleroderma may be associated with development of substantial disability, as occurs in deep morphea and in pediatric patients (disabling pansclerotic morphea of children). We report a case of morphea profunda affecting a young man with severe, rapidly progressive, widespread skin involvement and focus on the eventual systemic evolution of such cases. A 40-year-old man was admitted in 2002 for progressive subcutaneous indurations, preferentially involving the right side of the trunk. His health was altogether good, with the exception of a beginning chronic obstructive bronchopneumopathy. There was no family or personal history of dysmetabolic, cardiovascular, neoplastic, or cutaneous disease. Three years earlier, the patient had noted the appearance of two infiltrated, intensely red lesions on the right laterocervical and paraumbilical regions. These had been interpreted as subcutaneous lipomatosis on the basis of an ultrasound scan. The lesions had become progressively larger, while their surface had assumed a scleroatrophic appearance. Thereafter, other lesions had developed on his chest and lower limbs, mostly distributed on the right side of the body. Clinical examination revealed well demarcated, depressed sclerotic plaques with ivory-colored centers and erythematous borders ("lilac ring") localized on the neck, chest, and lower abdomen and limbs (Figure 1). They were bound to the deeper structures and arranged in a band-like linear distribution on the right side of the chest and abdomen where they extended horizontally for more than 10 cm in diameter. These lesions were totally asymptomatic. In addition, arborizing telangiectasias were evident on the neck and upper chest (Figure 2). Laboratory investigations provided normal range of erythrocyte sedimentation rat and C reactive protein levels and other inflammation markers. Antinuclear antibody, antidouble-strand DNA, antimitochondrial, anti-extractable antigens (anti-centromere, anti-Scl-70, anti-U1RNP), and anti-Borrelia burgdorferi antibodies were negative. Circulating immunocomplexes binding C1q were substantially increased. Oesophageal x-rays and lower limb electromyography were within normal limits; ventilatory function testing revealed a mild obstruction consistent with the beginning of chronic obstructive pulmonary disease. Although nailfold capillaroscopy documented nonspecific findings of connective tissue disease (mega-capillaries, segmentary dilatation and destruction), the laser-Doppler flussimetry revealed few signs of microcirculatory abnormalities, in absence of Raynaud's phenomenon. An abdominal wall ultrasonography, performed on a sclerotic plaque, documented thinning of the subcutaneous tissue, with increase of the fibrous component and lower fascia and muscle retraction. The biopsy specimen from the abdominal region included fascia and the subcutaneous tissue (previously obtained from the lower abdomen) with epidermal atrophy, a thickening and homogenization of collagen bundles in the deep dermis and hair reduction. A perivascular lympho-monocytic and plasmacellular infiltration with a dermo-epidermal distribution was present. Moreover, septal fibrosis with a perivascular lymphoplasmacellular inflammatory infiltrate was documented within the abdominal rectus muscle. The diagnosis of morphea profunda was made on the basis of clinical and histopathological findings. A therapeutic regimen based on amino benzoic potassium (Potaba; Glenwood, LLC, Glenwood, NJ), oral prednisone, and topical clobetasol was started. After several months of follow-up, the patient had obtained only moderate improvement of the clinical findings.

Chronic idiopathic urticaria: infiltrating cells and related cytokines in autologous serum-induced wheals.

The term chronic autoimmune urticaria (CAIU) is used for chronic urticaria in subjects who present a whealing response to the intradermal injection of autologous serum, suggesting the presence of pathogenic antibody activities. In this study, we examined 28 chronic urticaria subjects with positive autologous serum skin test (ASST), all of whom presented autologous serum-induced lesions at different evolutive stages. Punch biopsies were taken from lesional skin of six subjects at 10', eight subjects at 30', six subjects at 60', and four subjects each at 24 and 48 h. Immunological studies focussed on infiltrating cell immunophenotype and related cytokines, chemokines and chemokine receptors, adhesion molecules. Immunohistochemical staining was performed to measure expression of CD3, CD4, CD8, tryptase, eosinophil cationic protein, myeloperoxidase, basophil granular protein, IL-4, IL-5, IL-8, CCR3 and CXCR3, ICAM-1, VCAM and ELAM. Control staining was done on unaffected skin from the patients and normal skin from four healthy donors. The main infiltrating population was represented by neutrophils, seen focally in both unaffected skin (P = 0.001) and healthy controls (P = 0.003). IFN-gamma and IL-5 were expressed focally in autologous wheals. Significant staining for IL-4 was seen at 30'. CCR3 and CXCR3 were expressed less in autologous wheals than in uninvolved skin (P < 0.0001; P = 0.002). Cellular adhesion molecules (CAMs) reached their highest expression at 30' and 60' in induced lesions, and they showed strong expression also in unaffected skin (ICAM-1: P < 0.0001). Our data show that the immunoinflammatory features of ASST-induced wheals involve a prevalent role of lymphocytes (with a mixed Th1/Th2 response), with strong neutrophil infiltration and activity and involvement of the chemokine pathway. We interpreted the finding of inflammatory cells and mediator up-regulation in uninvolved CIU skin as a sign of prolonged and widespread "urticarial status".

A case of lichenoid drug eruption associated with sildenafil citratus.

A 53-year-old man developed lichenoid lesions on the upper chest, posterior surfaces of the trunk, and abdominal region about three months before his first visit. Physical examination and laboratory findings were normal; histopathology showed vacuolar degeneration of basal keratinocytes in association with a dense lympho-histioid infiltrate arranged in a lichenoid pattern with a few melanophages and eosinophils. The fact that our patient had been irregularly taking sildenafil citratus (Viagra) led to the hypothesis of a lichenoid drug-induced eruption. Our hypothesis was confirmed by clinical resolution three weeks after discontinuation of sildenafil citratus; moreover, the patient avoided the drug for about four months, and the eruption didn't reappear. Subsequently, we performed a challenge test with the drug, and the patient developed similar lichenoid lesions. Lichenoid eruptions are rather common dermatoses that can be induced by a great number of environmental agents and are clinically but not pathogenetically well defined. We report the present case because, despite the great number of drugs that can be implicated in the development of lichenoid eruptions, the association of such dermatoses and sildenafil citratus had been described only once previously in the literature until now. Furthermore, we wish to remark on the significance of a detailed anamnestic history to make the correct differential diagnosis between lichenoid drug-induced eruptions and lichen planus. This has a great clinical importance because simple discontinuation or substitution of the drug causes lichenoid drug-induced eruption resolution.

A case of nodular scleroderma.

Nodular scleroderma is a rare complication of systemic sclerosis; the pathogenetic implications are still unknown, although many factors are supposed to play a role in lesion development. We report the case of a young woman suffering from systemic sclerosis, who developed nodular lesions during therapeutic management with D-penicillamine and plasmapheresis. In order to better understand the essence of this disease, we examined all the possible pathogenetic mechanisms that could be implicated in nodular lesion development.

Systemic lupus erythematosus with unusual maculopapular and erosive cutaneous lesions.

In 2002, a 38-year-old woman was referred to the department of dermatological sciences for the evaluation of erythematous-infiltrated lesions with prominent purpuric and erosive components distributed on her face, upper chest, and extensor surfaces of the limbs, which developed over a 3-month period. In 1997 the patient suffered from polyarthralgia (proximal interphalangeal,knee, wrist, and metacarpophalangeal joints) associated with morning stiffness. In 1999 she was admitted to a psychiatric unit for depression with episodes of lipothymia. In the same year, since she developed diffuse and persistent urticarial manifestations with angioedema and livedo reticularis of the limbs in association with anticardiolipin antibodies, vasculitis was proposed. Upon examination, erythematous-infiltrated and erosive lesions in association with serohemorrhagic crusts were present on the face,neck, chest, upper trunk, and extensor surfaces of the upper limbs and thighs (Figures 1-3). Telangiectasias were especially evident on the cheeks, where prominent edema conferred her face a moon-like appearance (Figure 1). Laboratory investigations disclosed microcytic anemia, elevated erythrocyte sedimentation rate, proteinuria (30 mg/dL), positive antinuclear antibodies (1:80) with diffuse fluorescence pattern, lowered complement levels (C3: 31 mg/dL, C4: 3 mg/dL), circulating immunocomplexes binding Clq, and high titers of anti-TSH receptor antibodies. Indirect immunofluorescence was negative for the detection of anti-basement membrane zone antibodies. Histological examination of the lesional skin of the shoulder documented epidermal atrophy, marked vacuolar degeneration of the basal cell layer, colloid bodies, and a perivascular lymphohistiocytic infiltration of the upper and deep dermis (Figure 4). Direct immunofluorescence performed on affected skin showed junctional granular deposition of IgG, C3,and Clq in association with perivascular C3 and Clq deposits in the upper dermis; direct immunofluorescence on sun-protected,non-lesional skin showed similar immunological deposition both at the basement membrane zone and in the perivascular dermis.Based upon the clinical, histologic, and immunopathologic findings, we proposed the diagnosis of systemic lupus erythematosus with maculopapular and erosive skin lesions. The patient was treated with methylprednisolone IV (pulse therapy, 250 mg) tapered over 10 days and later continued p.o. After a few weeks, significant improvement of cutaneous manifestations was noted.

Chronic idiopathic and chronic autoimmune urticaria: clinical and immunopathological features of 68 subjects.

Skin tests with autologous serum elicit an immediate wheal-and-flare response in about 30-50% of chronic idiopathic urticaria subjects, suggesting that an autoimmune mechanism might be involved in the pathogenesis of this disease. The aim of the present work, involving 68 subjects with chronic idiopathic urticaria, was to distinguish between the serum-positive and serum-negative cases and highlight the clinical differences between the two groups on the basis of the Breneman scale score. We also tried to correlate the finding of a positive response to the autologous serum skin test with other autoimmune diatheses or fully developed autoimmune disorders. Our results did not demonstrate any significant differences between the two groups with regard to mean age, sex distribution, angioedema and mucosal/cutaneous atopy. However, all subjects with positive autologous serum skin test presented more severe clinical features than serum-negative subjects. We found no differences between the two groups in the incidence of autoimmune disease.