Lupus Erythematosus Tumidus Associated With Hemophagocytosis.

ABSTRACT: A case of lupus erythematosus tumidus (LET), a subtype of chronic cutaneous lupus erythematosus, in an 85-year-old woman who presented with discrete indurated erythematous plaques over the face and upper chest is described. A skin biopsy showed features in keeping with a diagnosis of LET. Unusually however, the lymphocytic infiltrate contained frequent macrophages that demonstrated hemophagocytosis. Most of the phagocytosed cells were lymphocytes, but there was also evidence of erythrophagocytosis. The presence of conspicuous hemophagocytosis has only rarely been reported in skin biopsies of patients with autoimmune conditions. These include systemic lupus, neonatal lupus and dermatomyositis, and on 2 occasions in cases of nonspecified cutaneous lupus erythematosus. To the best of our knowledge, hemophagocytosis as a feature of LET has not been previously described in the literature.

Occupational Localized Cutaneous Argyria With Pseudo-Ochronosis in a Jeweler.

ABSTRACT: A case of localized argyria in a 36-year-old female jeweler is described who presented with 2 discrete and asymptomatic bluish-black pigmented macules on the pulp of her left middle finger. A skin biopsy from both lesions demonstrated deposition of brown/black pigmented granules along the basement membrane zone of eccrine glands, blood vessels, nerves, and the dermo-epidermal junction fully in keeping with silver deposition. In addition, there was yellow-brown deposition seen within the interstitial dermis mimicking an early form of ochronosis, so called "pseudo-ochronosis." This latter feature is rarely described in cases of argyria. Transmission electron microscopy and energy dispersive x-ray spectroscopy confirmed the presence of electron dense particles up to 150 nm in diameter and the presence of silver, respectively. On further questioning, the patient had a history of localized and chronic exposure to silver, which specifically involved holding and manipulating silver wires and rings over the left middle finger. This case highlights an unusual and rare presentation of localized argyria in a jeweler. In addition, our case showed preferential silver deposition on dermal elastic fibers which has not been previously described in the literature.

Angiomatoid Fibrous Histiocytoma With ALK Expression in an Unusual Location and Age Group.

Angiomatoid fibrous histiocytoma (AFH) is a relatively rare soft tissue tumor of intermediate malignant potential, occurring most commonly in young adults, with a recognized propensity for local recurrence and occasional metastasis. A case of AFH occurring on the finger of a 60-year-old man is described in which the unusual location and age group for this entity raised the original wrong diagnosis of an aneurysmal and cellular fibrous histiocytoma. Further workup demonstrated an EWSR1-CREB1 translocation, confirming the correct diagnosis of AFH. Strong anaplastic lymphoma kinase (ALK) expression using the antibody clone D5F3 was demonstrated in our case on immunohistochemistry, which is in concordance with recent findings of anaplastic lymphoma kinase positivity with this antibody in the majority of AFHs.

Lichen Planus Pemphigoides Mimicking Toxic Epidermal Necrolysis.

Lichen planus pemphigoides (LPP) is an immunobullous disorder characterized by a combination of lesions resembling bullous pemphigoid and lichen planus (LP). Immunofluorescence studies typically show linear deposition of IgG and C3 along the basement membrane zone and circulating antibodies to the hemidesmosome protein BP180 also known as type XVII collagen. It is now recognized that drug-induced linear IgA disease may present with lesions mimicking toxic epidermal necrolysis (TEN). However, to date, there have been no reported cases of LPP presenting with TEN-like lesions. This report describes a 70-year-old woman with LPP who presented with extensive erosions mimicking TEN. This case also highlights the need to consider important etiologies such as drug-induced and paraneoplastic LPP.

'Hints' in the horn: diagnostic clues in the stratum corneum.

The stratum corneum or horny layer is the uppermost layer of the epidermis, and is mainly responsible for the skin's barrier function. In spite of its complexity at the ultrastructural and molecular level, the features accessible to visualization on conventional histology are relatively limited. Nevertheless, knowledge of subtle clues that one may observe in the stratum corneum can prove useful in a wide range of situations in dermatopathology. We herein review a selection of common and rare entities in which the horny layer may reveal significantly important hints for the diagnosis. These clues include parakeratosis and its different patterns (focal, confluent, alternating, associated with spongiosis, epidermal hyperplasia or lichenoid changes), subcorneal acantholysis, infectious organisms in the stratum corneum (including fungal, bacterial and parasitic), thickening or thinning of the stratum corneum and the presence of different kinds of pigment. Even when normal, the horny layer may prove to be useful when seen in association with severe epidermal damage, a combination of features testifying to the acute nature of the underlying pathological process.

Epidermolysis Bullosa Acquisita (Brunsting-Perry Pemphigoid Variant) Localized to the Face and Diagnosed With Antigen Identification Using Skin Deficient in Type VII Collagen.

Brunsting-Perry pemphigoid is defined as an autoimmune vesiculobullous eruption typically localized on the head and neck region with minimal or no mucosal involvement. The disease tends to run a chronic and recurrent course with residual scarring. Histological features are characterized by subepidermal bullae and linear IgG deposits at the dermo-epidermal junction. We report a case of a 46-year-old lady who presented with typical features of Brunsting-Perry pemphigoid. Autoantibodies to type VII collagen were identified by using recessive dystrophic epidermolysis bullosa skin which lacks type VII collagen in an indirect immunofluorescence assay. As a result, we diagnosed our patient as having the Brunsting-Perry pemphigoid variant of epidermolysis bullosa acquisita (EBA). This finding led us to review the literature on target antigens in Brunsting-Perry pemphigoid. Only 11 out of the 58 cases reported to date had target antigens identified. Interestingly, type VII collagen was the second most common target antigen/autoantibody (4 cases) detected after BP180 (5 cases). However, 2 further cases of EBA localized to the face with typical features of Brunsting-Perry pemphigoid were found in the literature. Although the target antigens are heterogeneous in Brunsting-Perry pemphigoid, a significant number of cases represent a clinical presentation of localized EBA.

Histological Features of Methylene Blue-Induced Phototoxicity Administered in the Context of Parathyroid Surgery.

Methylene blue is a chromophore dye known for its photosensitizing properties. It is also administered intravenously as a tracer in parathyroid surgery to identify abnormal glands. We describe 2 cases of acute methylene blue-induced phototoxicity in patients who underwent parathyroidectomy. Both patients developed an acute vesiculopustular inflammatory rash on the anterior neck corresponding to the site exposed intraoperatively to overhanging surgical lights. One of the patients also developed a bulla on her finger at the site of attachment of the oxygen probe. Biopsies were taken from both patients at different time points. The histological findings included destruction of sebaceous glands and deposition of diastase-periodic acid-Schiff-positive hyaline material around dermal blood vessels. These features are similar to those seen in skin treated with photodynamic therapy and systemic photosensitivity disorders such as the porphyrias. The wavelengths of light emitted by the surgical lights and oxygen probe overlap with the absorption spectrum of methylene blue. This resulted in excitation of the systemically administered methylene blue at exposed sites, with resultant local tissue damage and a phototoxic reaction.

RNA-seq analysis of host and viral gene expression highlights interaction between varicella zoster virus and keratinocyte differentiation.

Varicella zoster virus (VZV) is the etiological agent of chickenpox and shingles, diseases characterized by epidermal skin blistering. Using a calcium-induced keratinocyte differentiation model we investigated the interaction between epidermal differentiation and VZV infection. RNA-seq analysis showed that VZV infection has a profound effect on differentiating keratinocytes, altering the normal process of epidermal gene expression to generate a signature that resembles patterns of gene expression seen in both heritable and acquired skin-blistering disorders. Further investigation by real-time PCR, protein analysis and electron microscopy revealed that VZV specifically reduced expression of specific suprabasal cytokeratins and desmosomal proteins, leading to disruption of epidermal structure and function. These changes were accompanied by an upregulation of kallikreins and serine proteases. Taken together VZV infection promotes blistering and desquamation of the epidermis, both of which are necessary to the viral spread and pathogenesis. At the same time, analysis of the viral transcriptome provided evidence that VZV gene expression was significantly increased following calcium treatment of keratinocytes. Using reporter viruses and immunohistochemistry we confirmed that VZV gene and protein expression in skin is linked with cellular differentiation. These studies highlight the intimate host-pathogen interaction following VZV infection of skin and provide insight into the mechanisms by which VZV remodels the epidermal environment to promote its own replication and spread.

Chromoblastomycosis Treated With Posaconazole and Adjunctive Imiquimod: Lending Innate Immunity a Helping Hand.

Chromoblastomycosis (CBM) is a difficult-to-treat, chronic fungal infection of the skin and subcutaneous tissue. The evidence base for treatment is scarce, with no standardized therapeutic approach. Chronicity of CBM infection is postulated to be due in part to a failure of host cell-mediated immunity to generate a proinflammatory response sufficient for fungal clearance. We present a case of a chronic chromoblastomycosis lesion of the hand present for nearly 4 decades, previously refractory to itraconazole monotherapy, that was successfully treated with a combination of posaconazole and adjunctive immunotherapy with topical imiquimod, a Toll-like receptor 7 agonist. Serial biopsies and images demonstrate the clinical and histopathological improvement of the lesion. Randomized trials of antifungal therapy with adjunctive imiquimod are warranted to determine whether a combination of antifungal and host-directed therapy improves outcomes for this neglected tropical mycosis.

Subungual Exostosis Presenting as a Pyogenic Granuloma-like Lesion with Reactive Myofibroblastic Proliferation in Two Young Women.

Subungual exostosis (SE) is a well-recognised benign proliferation of the distal phalanx most often seen in young adults and affecting the big toe. Possible triggers include previous trauma and chronic irritation or infection. We describe two atypical cases of SE in two young women presenting with pyogenic granuloma-like lesions clinically. Diagnostic biopsies were performed to confirm the diagnosis and excluded amelanotic melanoma. However, histology unexpectedly revealed reactive myofibroblastic proliferations mimicking nodular fasciitis overlying the SE. Given the atypical clinical presentation, the diagnosis was initially missed or not considered in both patients. They highlight two important points; the first is that SEs may present with pyogenic granuloma-like lesions clinically and that histological analysis is then required to exclude malignancy, particularly amelanotic melanoma. Secondly, that the histology will show a reactive myofibroblastic proliferation and if the sample is relatively superficial and pathologists are not aware of this potential reaction pattern, the underlying diagnosis of SE may be missed.

Acute sun damage and photoprotective responses in whales.

Rising levels of ultraviolet radiation (UVR) secondary to ozone depletion are an issue of concern for public health. Skin cancers and intraepidermal dysplasia are increasingly observed in individuals that undergo chronic or excessive sun exposure. Such alterations of skin integrity and function are well established for humans and laboratory animals, but remain unexplored for mammalian wildlife. However, effects are unlikely to be negligible, particularly for species such as whales, whose anatomical or life-history traits force them to experience continuous sun exposure. We conducted photographic and histological surveys of three seasonally sympatric whale species to investigate sunburn and photoprotection. We find that lesions commonly associated with acute severe sun damage in humans are widespread and that individuals with fewer melanocytes have more lesions and less apoptotic cells. This suggests that the pathways used to limit and resolve UVR-induced damage in humans are shared by whales and that darker pigmentation is advantageous to them. Furthermore, lesions increased significantly in time, as would be expected under increasing UV irradiance. Apoptosis and melanocyte proliferation mirror this trend, suggesting that whales are capable of quick photoprotective responses. We conclude that the thinning ozone layer may pose a risk to the health of whales and other vulnerable wildlife.