No abstract

We reviewed the histologic and direct immunofluorescence findings in skin biopsy specimens from 24 patients with cutaneous porphyrias. The histopathologic changes were characterized by cell-poor subepidermal bullae, festooning of dermal papillae, thickening and hyalinization of dermal blood vessel walls, dermal sclerosis, and a mild perivascular infiltration of mononuclear cells in the upper dermis. The characteristic pattern on direct immunofluorescence testing was fluorescence of thickened doughnut-like blood vessels in the upper dermis, reflecting deposition of immunoglobulins and C3, and deposition of immunoglobulins or C3 or both at the dermal-epidermal junction in most cases. These findings are characteristic but not specific for the porphyrias; they may also be observed in the pseudoporphyria syndromes and in other clinical settings. However, the immunopathologic findings are distinctive enough to be useful in differentiating the porphyrias and pseudoporphyria syndromes from other subepidermal bullous diseases such as epidermolysis bullosa acquisita and bullous pemphigoid. The most important diagnostic test in the evaluation of the cutaneous porphyrias still is measurement of porphyrins in urine, stool, and blood.

A 53-year-old man was transferred to our intensive care unit for a generalized exanthem with systemic inflammatory response syndrome. His medical history included a possible disseminated infection of herpes zoster 15 years before the current admission. He had no history of psoriasis, cutaneous drug reaction, immune suppression or heart disease. Before the current incident, he had not been using any prescribed or over-the-counter medications.Seven days before admission, the patient was bitten on his finger by a spider. He reported pain at the site, and there was a necrotic crust. His primary care physician prescribed cefprozil. A few hours after the first dose, a rash developed. The rash was described as a generalized exanthem with nonfollicular superficial pustules and fever. Based on a working diagnosis of recurrent herpes zoster, he was given famciclovir.Two days before admission to our intensive care unit, the patient was admitted to another centre with high fever, fatigue and persistent skin lesions. Because of fever, leukocytosis and pustules, an infectious cause was suspected. Antibiotic coverage was broadened to include piperacillin-tazobactam and moxifloxacin. The results of tests for infectious and immunosupressive diseases were negative. A computerized tomography (CT) scan of the patient's chest showed alveolar opacities with a ground-glass appearance in both upper lungs. A CT scan of the patient's abdomen showed small nonspecific opacities in his liver. The patient was then transferred to our centre.When the patient arrived at our centre, he had a fever (39.9°C) and was tachycardic (130 beats/min) and hypotensive (90/80 mm Hg). His oxygen saturation was 90% on room air. There was no jugular venous distension. The results of a cardiac examination were unremarkable, except for tachycardia. More than 80% of his skin, including his face and scalp, was affected by a generalized erythema with multiple small nonfollicular pustules. An examination of his mucous membranes showed redness of his tongue. He did not have the Nicolsky sign. (The Nikolsky sign is detected by applying pressure to the skin, which causes intraepidermal cleavage that allows the superficial skin to slip free from the deeper layer. It is mainly seen with bullous diseases and toxic epidermal necrolysis.)Important laboratory results are shown in Table 1. An electrocardiogram showed only sinus tachycardia. We suspected a cutaneous drug reaction. The main diagnoses considered at that time were Stevens-Johnson syndrome or toxic epidermal necrolysis and acute generalized exanthematous pustulosis associated with severe systemic inflammatory response syndrome. The results of the CT scan of the patient's chest were suggestive of an acute lung injury. An infectious cause was not likely because all of the cultures were negative. Antibiotics were discontinued, and fluid resuscitation was initiated. A few hours after admission, our patient developed pulmonary edema with acute respiratory failure. Noninvasive positive pressure ventilation and diuretic ...

Th17 cells have been implicated in a number of inflammatory and autoimmune diseases. The phospholipid mediator platelet-activating factor (PAF) is found in increased concentrations in inflammatory lesions and has been shown to induce IL-6 production. We investigated whether PAF could affect the development of Th17 cells. Picomolar concentrations of PAF induced IL-23, IL-6, and IL-1β expression in monocyte-derived Langerhans cells (LCs) and in keratinocytes. Moreover, when LC were pretreated with PAF and then cocultured with anti-CD3- and anti-CD28-activated T cells, the latter developed a Th17 phenotype, with a significant increase in the expression of the transcriptional regulator RORγt and enhanced expression of IL-17, IL-21, and IL-22. PAF-induced Th17 development was prevented by the PAF receptor antagonist WEB2086 and by neutralizing antibodies to IL-23 and IL-6R. This may constitute a previously unknown stimulus for the development and persistence of inflammatory processes that could be amenable to pharmacologic intervention.

We report on a case of Schnitzler's syndrome, focusing on pattern of bone involvement and its differential diagnosis.