Ana Maria Abreu Velez

Antibodies to pilosebaceous units along their neurovascular supply routes in a new variant of endemic pemphigus foliaceus in Colombia, South America.

Senear Usher syndrome is a variant of pemphigus foliaceus, confined to seborrheic sites and considered to be a clinical overlap syndrome, with features of both pemphigus foliaceus and lupus erythematosus. We recently described autoantibodies to skin eyelid meibomian glands in patients with a new variant of endemic pemphigus foliaceus (El Bagre EPF) in South America. We tested for El Bagre EPF patient sera autoreactivity to pilosebaceous units utilizing direct and indirect immunofluorescence, confocal microscopy, immunohistochemistry and immunoelectron microscopy. Hematoxylin and eosin staining of skin biopsies revealed that one third of the patients affected by El Bagre-EPF demonstrated some histologic alteration of the pilosebaceous units. By immunohistochemistry, most El Bagre EPF biopsies demonstrated evidence of an autoimmune response along the neural and vascular supply routes of the pilosebaceous units. An active immune response was seen with antibodies such as anti-human mast cell tryptase, myeloid/histoid antigen, CD8, CD20, CD68, CD117/c-kit, ZAP-70 and vimentin. Immunoelectron microscopy demonstrated autoantibodies within the hair follicle and at the basement membrane area of the sebaceous glands. El Bagre-EPF patients have autoantibodies to pilosebaceous units and to their surrounding neurovascular packages. Our results warrant further characterization and may explain the loss of hair described in severe endemic pemphigus foliaceus before the therapeutic steroid era.

Deposition of immunoreactants in a cutaneous allergic drug reaction

Context: The analysis of allergic drug reaction pathology may be difficult, especially if multiple histological reaction patterns are detected on review of hematoxylin and eosin (H&E) stained sections. In this case, we emphasize the value of adding immunohistochemistry (IHC) and multicolor direct immunofluorescence (DIF) as tools to improve the diagnosis of these complex disorders. Patient and Methods: Our patient is a twenty-year-old Caucasian female, who presented with a sudden onset of erythematous macules on the skin following administration of amoxicillin. Lesional tissue was examined by H & E and IHC, and perilesional tissue by DIF and IHC. Results: The H&E findings revealed diffuse dermal edema, and a mild, superficial, perivascular dermatitis with a mixed inflammatory infiltrate, consistent with an allergic drug eruption. The IHC and DIF studies revealed autoreactivity to sweat glands, nerves and dermal blood vessels, as well as dermal deposits of immune reactants such as fibrinogen and complement around the inflamed areas. Conclusions: Fibrin-fibrinogen degradation products have been shown in some cases of allergic disorders; thus, we encourage the effect further testing for these immunoreactants in biopsies from patients with possible allergic drug reactions.

Varicella-zoster virus (VZV) and alpha 1 antitrypsin: a fatal outcome in a patient affected by endemic pemphigus foliaceus

Background  Herpes virus infections are well known infectious complications of pemphigus and bullous pemphigoid. We describe pathologic findings utilizing autopsy tissue from several organs from a patient affected by a new variant of endemic pemphigus in El Bagre, Colombia, South America.

HAM56 and CD68 antigen presenting cells surrounding a sarcoidal granulomatous tattoo.

Context Tattoos are produced by introducing colorants of various compositions into the skin, either accidentally or for cosmetic purposes. Case Report: A 62-year-old male presented with a cosmetic tattoo and requested a total excision of the lesion. Dermatopathologic analysis of the excised tissue with hematoxylin and eosin examination, as well as immunohistochemistry was performed. H&E staining demonstrated classic histologic features of a tattoo. Utilizing immunohistochemistry, dermal histiocytic antigen presenting cells stained with HAM56 and CD68 antibodies; the staining was present surrounding the tattoo pigment. Conclusions We identified two macrophage markers (HAM56 and CD68) surrounding dermal tattoo pigment. A minimal dermal inflammatory immune was noted to the tattoo pigment. Moreover, the immune response and/or tolerance to tattoos is not well characterized. We suggest that tattoo materials and techniques could be utilized in therapeutic delivery for diseases such recessive dystrophic epidermolysis bullosa, potentially preventing immune rejection of gene therapy agents.

Formalin deposition as artifact in biopsies from patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America

Background: Most autoimmune diseases occur sporadically; however, endemic pemphigus foliaceus (EPF) is present in specific locales restricted to some geographic rural regions mostly in South America, Central America and in Tunisia (Africa). Its geographic restriction makes it an invaluable natural model for studying how the environment, genetic background and host response contribute to the development of autoimmunity. We described a new variant of EPF in El Bagre, Colombia, (El Bagre‐EPF). When we examined the skin biopsies from 10 patients and controls from the endemic area, we detected in a systematic manner several types of pigmentation, sometimes intracellular, and sometimes in the extracellular matrix in most biopsies.

Immune reactivity in psoriatic Munro-Saboureau microabscesses, stratum corneum and blood vessels

Background: A characteristic feature of early active psoriatic lesions is the intraepidermal penetration of neutrophils, with attendant formation of Munro-Saboureau microabscesses. Previous immunofluorescence studies have shown reactivity of in vivo binding of stratum corneum antibodies (SCAs) within the Munro-Saboreau microabscesses in cases of psoriasis. Aims: In our study, we aimed to investigate any correlation between the SCAs and the Munro-Saboureau microabscesses. Materials and Methods: We investigated 50 archival biopsies of psoriasis with Munro-Saboureau microabscesses, and attempted to confirm antibody colocalization within these microabcesses via immunohistochemistry staining. As controls, we utilized 50 skin biopsies from healthy patients undergoing esthetic plastic surgery procedures. Results: Within the Munro-Saboureau microabscesses, the following markers were statistically significantly positive relative to controls: CD1a, CD8, CD23, cyclooxygenase-2, myeloid histoid antigen, albumin, fibrinogen, kappa, lambda, von Willebrand factor, IgG, IgM, IgD, complement/C3c, C3d, myeloperoxidase, and carcinoembryonic antigen (P < 0.05). Autoreactivity to blood vessels was also detected, with multiple immunoglobulins and complement factors. Conclusions: We document important correlations between the Munro-Saboureau microabscesses, SCAs, and other immunoreactants.

An inflamed trichilemmal (pilar) cyst: Not so simple?

Context: Trichilemmal (pilar) cysts are common skin lesions that often present on the scalps of mature men and women. These cysts often become inflamed when the wall of the cyst ruptures, but few reports have addressed the immunologic features of this process. Case Report: A 22-year-old female presented with rapidly growing nodule on her left cheek, with evidence of acute inflammation. Skin tissue for hematoxylin and eosin examination, as well as for immunohistochemical analysis was taken and reviewed. As controls, we utilized two archival, non-inflamed trichilemmal cysts. Hematoxylin and eosin staining demonstrated classic features of an inflamed trichilemmal cyst. No cytologic atypia was noted, and no significant number of mitotic figures was identified. Immunohistochemistry stains revealed that several cell cycle/tumor suppressor/apoptotic markers, antigen presenting cell markers, metalloproteinases and T cell response markers were highly expressed inside and around the disrupted cyst. The control, non-inflamed cysts were negative for the same markers. CD1a was also appreciated within the epidermis, suprajacent to the inflamed cyst. Conclusions: Upregulation and/or downregulation of selected cell cycle regulator and/or tumor suppressor/apoptotic markers, as well as antigen presenting cells and some protein kinases could recruit and activate T lymphocytes and other inflammatory cells to the non-disrupted cyst for unknown reasons. The immune response may be involved in the initial cyst rupture, or induced by an unknown alteration in the cyst. Larger studies are needed to address these questions.

Autoantibodies to melanocytes and characterization of melanophages in patients affected by a new variant of endemic pemphigus foliaceus

Background: Melanin and melanophages are commonly seen under the basement membrane zone of the skin in patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre‐EPF).

Jam-A, Plasminogen and Fibrinogen Reactivity in a Case of a Lupus Erythematosus-Like Allergic Drug Reaction to Lisinopril

Background: Drug-induced lupus erythematosus is a lupus variant that resolves within days to months after withdrawal of the eliciting drug, in patients without other major underlying immune system dysfunction. Case report: A 71 year old Caucasian female presented following sudden onset of an erythematous, desquamative, polycyclic, scaling and pruritic rash in sun exposed areas, 4 days after taking Lisinopril®. Skin biopsies for hematoxylin and eosin analysis, as well as for direct immunofluorescence (DIF) were obtained. Results: The hematoxylin and eosin staining revealed basal layer vacuolar degeneration, basilar apoptotic and dyskeratotic keratinocytes, and a lymphocytic interface dermatitis with an additional superficial and deep, perivascular and periadnexal lymphohistiocytic infiltrate. A significant presence of eosinophils was noted in the inflammatory infiltrate. DIF demonstrated positive reactivity with FITC conjugated anti-human fibrinogen, especially directed against dermal neurovascular plexus components and appendageal neurovascular supply structures; this staining colocalized with glial fibrillary acidic protein staining. Overexpression of anti-plasminogen and anti-junctional adhesion molecule A was also noted in these areas. Conclusion: In this case of a lupus-like allergic drug reaction, the strong presence of dermal eosinophils, lack of basement membrane zone deposition of IgM and C3 and strong reactivity to dermal vessels with fibrinogen assisted in addressing the differential diagnosis of lupus erythematosus.