Generalized granuloma annulare and drug-induced immunodeficiency

BACKGROUND: Granuloma have already been described in the context of immunosuppression. We report six cases of widespread granuloma annulare occurring in patients with drug-induced immunosuppression. CASE REPORTS: There were four women and two men, with mean age of 61 years (35-76). Three patients were treated with chemotherapy for breast (2 cases) and liver cancer. One woman was given chemotherapy for Hodgkin's disease. One had undergone liver transplantation and was given cyclosporine, another was treated with systemic steroids for polyarthritis. All had generalized non-photoexposed granuloma annulare, composed of multiple erythematous papules, sometimes with annular pattern. The lesions were localized on the trunk, legs and arms. Histopathology revealed granuloma annulare in each patient. DISCUSSION: These six cases suggest a relationship between drug-induced immunodeficiency and generalized granuloma annulare. The immune dysregulation induced by the drugs may have been responsible for the formation of granuloma annulare.     

CD1a molecules traffic through the early recycling endosomal pathway in human Langerhans cells

In this work, we studied the localization and traffic of CD1a molecules in human epidermal Langerhans cells and the ability of these cells to stimulate CD1a-restricted T cell clones. We found that CD1a was spontaneously internalized into freshly isolated Langerhans cells, where it was rapidly distributed to the early/sorting endosomes and then to the early/recycling endosomes. In the latter compartments, CD1a colocalized with Rab11, a small GTPase known to be involved in the recycling of transmembrane proteins from early endosomes to the cell surface. In the steady state, intracellular CD1a was mainly located in Rab11+ recycling endosomal compartments. When endocytosis was blocked, intracellular CD1a moved rapidly from the early/recycling endosomes to the cell surface where it accumulated. The resultant increase in the cell surface expression of CD1a enhanced the capacity of Langerhans cells to stimulate a CD1a-restricted T cell clone. These findings are consistent with a dynamic exchange of CD1a between recycling compartments and the plasma membrane and suggest that the antigen-presenting function of CD1a depends on its traffic through the early/recycling endosomal pathway.     

Jessner�CKanof disease induced by leflunomide: a dermal variant of cutaneous lupus?

Leflunomide can have adverse effects, but cases of subacute cutaneous lupus have more rarely been described. This drug, through its immunomodulatory effect, can favor the appearance of a Th2 lymphocyte immune response inducing lupus. A recent study has suggested that Jessner–Kanof disease (JKD) could be a dermal form of lupus. We report a case of subacute cutaneous lupus induced by leflunomide with anti-Ro/SSA Ab and unusual histological presentation, identical to that of JKD. Leflunomide can induce cutaneous lupus characterized by exclusively dermal involvement and histologically comparable to JKD. This observation therefore suggests that JKD could be a dermal variant of lupus. This prompted a revision of the classification of cutaneous lupus, which has until now been divided into acute, subacute and chronic forms but could equally be classed as epidermal, dermal and hypodermal. The last point of interest in our observation is the efficacy of a combination of chloroquine and anakinra, which led to complete remission of the articular and cutaneous symptoms after the failure of corticotherapy.     

How not to miss autoinflammatory diseases masquerading as urticaria

Urticarial skin reactions are one of the most frequent problems seen by allergists and clinical immunologists in daily practice. The most common reason for recurrent wheals is spontaneous urticaria. There are, however, several less common diseases that present with urticarial rash, such as urticarial vasculitis and autoinflammatory disorders. The latter include cryopyrin‐associated periodic syndrome and Schnitzler's syndrome, both rare and disabling conditions mediated by increased interleukin‐1 secretion. Apart from the urticarial rash, patients are suffering from a variety of systemic symptoms including recurrent fever attacks, arthralgia or arthritis and fatigue. Autoinflammatory diseases are often associated with a diagnostic delay of many years and do not respond to antihistamines and other treatments of urticaria. Also, the chronic inflammation may lead to long‐term complications such as amyloidosis. It is therefore important not to miss these diseases when diagnosing and treating patients with chronic recurrent urticarial rash. Here, we present clinical clues and tips that can help to identify autoinflammatory disorders in patients presenting with chronic urticarial rash and discuss their clinical picture and management.     

Vulvar vestibulitis syndrome: a clinicopathological study of 14 cases

BACKGROUND: Vulvar vestibulitis syndrome (VVS) is one of the most frequent causes of superficial dyspareunia in young women. VVS has a pronounced psychological impact. The results of pathological studies published thus far are controversial. PATIENTS AND METHODS: Fourteen women with VVS were included in this study and underwent vestibular biopsy. Vulvar biopsies were taken from the orifice of Bartholin's gland. The biopsy samples were stained with a standard stain and PAS and 25 serial sections were prepared for each specimen. RESULTS: The mean patient age was 26 years and VVS had been present for a mean 30 months. Extensive inflammation of mononuclear cells was observed in the vulvar chorionic epithelium. This inflammation was seen mainly around the minor vestibular glands. Mild exocytosis of lymphocytes was noted in the vestibular glands and ducts. DISCUSSION: Most studies concerning this disease report chronic inflammation of the vulvar vestibular mucosa. This inflammation is seen mainly around the minor vestibular glands. We report the same pattern in our study. Moreover, we observed some exocytosis into the epithelium of minor vestibular glands and the excretory duct. This aspect has not been reported to date, further supporting the individual nature of this entity.