Expression of intercellular adhesion molecule-1 (ICAM-1) and OKM5 in UVA- and UVB-induced lesions in patients with lupus erythematosus and polymorphous light eruption

Pathological skin reactions were induced with both UVA and UVB in 12 patients with lupus erythematosus (LE) and with UVA in 7 with polymorphous light eruption (PMLE) but in none of the controls. Biopsy specimens taken from UV-induced lesions showed that in dermal infiltrates of LE cases CD4-positive cells predominated, whereas in the majority of PMLE cases CD8-positive cells predominated. Keratinocytes expressed intercellular adhesion molecule-1 (ICAM-1) in 7 of the 12 UVA- and in eight of the ten UVB-induced LE lesions, and in three of the UVA-induced lesions of PMLE patients. Three different staining patterns were found. In subacute cutaneous LE (SCLE) cases staining throughout the epidermis resembled that seen in genuine SCLE lesions. In discoid LE (DLE) lesions, the staining was most prominent in and near the basal cell layer. In the one systemic LE case and in the PMLE cases, ICAM-1 expression was seen only in association with epidermal spongiosis and T-cell infiltration. Keratinocytes did not express ICAM-1 in the controls or in the non-irradiated skin of the LE patients. In five on the UVA-induced lesions, in eight of the UVB-induced LE lesions and in one of the PMLE cases, keratinocytes expressed CD36. In four of the six LE lesions with fewer CD1a-positive cells, dendritic CD36-positive cells were seen in the epidermis. In conclusion, the pattern of activated keratinocytes and immunocompetent cells in the dermis was similar to that seen in genuine LE and PMLE lesions, but dissimilar to each other and to the controls. Keratinocytes in both UVA- and UVB-induced lesions in LE patients and in UVA-induced lesions of PMLE expressed ICAM-1 with a staining pattern resembling that seen in genuine lesions. This may help to explain the pathomechanism of these skin lesions.     

网状红斑黏蛋白病1例

患者男,26岁。面颈部、躯干、四肢皮疹1年。皮损组织病理示轻度角化过度,表皮水肿,真皮浅至中层毛细血管扩张充血,周围有较多单一核细胞浸润。阿新蓝染色见真皮乳头层及网状层大量黏蛋白样物质沉积。诊断:网状红斑黏蛋白病。     

Broad histopathologic patterns of non‐glabrous skin and glabrous skin from patients with a new variant of endemic pemphigus foliaceus‐part 1

A prospective, controlled epidemiologic survey performed in El Bagre, Colombia revealed a new variant of endemic pemphigus disease, occurring in a gold mining region. The disease resembled Senear‐Usher syndrome, and occurred in an endemic fashion. The aim of this study is to describe the most frequent histopathologic patterns in non‐glabrous skin and in glabrous skin observed in these patients, and their clinical correlation. The study was performed on non‐glabrous skin biopsies of 30 patients from the dominantly clinical affected areas (either on the chest, arms or face). Simultaneously, biopsies from the palms were obtained in 10 randomly chosen patients of the 30 total patients. The specimens were examined following hematoxylin and eosin (H&E) staining. The most common blisters observed were subcorneal, although in some cases intraspinous and subepidermal blisters were visualized. Our results showed a very heterogeneous pattern of histopathologic patterns in non‐glabrous skin, which seemed to correlate with the clinical features. The most common pattern was typical pemphigus foliaceus‐like, with some lupus erythematosus‐like features. A non‐specific, chronic dermatitis pattern prevailed in the clinically controlled patients taking daily corticosteroids. In the patients who have had the most severe and relapsing pemphigus, early sclerodermatous changes and scleredermoid alterations prevailed in their reticular dermis. In addition to the scleredermoid alterations, the reticular dermis showed a paucity of appendageal structures. On the contrary, in the palms, a similar pattern was seen in all cases, including thickening of the stratum corneum, hypergranulosis, edema in the papillary and reticular dermis and a dermal perivascular lymphocytic infiltrate. The direct immunofluorescence of the glabrous vs. the non‐glabrous skin also showed some differences. We conclude that the histopathologic features of this new variant of endemic pemphigus are complex, therefore, classical histopathologic features previously described for superficial, endemic pemphigus cannot be used alone to diagnose this disease. Howard MS, Yepes MM, Maldonado‐Estrada JG, Villa‐Robles E, Jaramillo A, Botero JH, Patiño PJ, Hashimoto T, Abreu‐Velez AM. Broad histopathologic patterns of non‐glabrous skin and glabrous skin from patients with a new variant of endemic pemphigus foliaceus‐part 1.     

Periadnexal Mucin as an Additional Histopathologic Feature of Chronic Eczematous Dermatitis

BackgroundCutaneous mucinoses are a heterogeneous group of disorders characterized by an abnormal amount of mucin in the skin. However, the pathomechanism of an excessive mucin deposition in the skin is still unknown. Eczematous dermatitis is sub-classified histologically into acute, subacute, and chronic variants. The characteristic histopathologic findings for chronic eczema are variable. However, periadnexal mucin deposition is not known as a feature of chronic eczema.ObjectiveTo evaluate the presence of periadnexal mucin deposition in chronic eczematous dermatitis.MethodsWe analyzed the skin biopsy specimens from 36 patients who were pathologically diagnosed with chronic eczematous dermatitis. Alcian blue, colloidal iron, and periodic acid-Schiff stains were used to evaluate the mucin deposition in histologic sections. Two dermatologists and two dermatopathologists evaluated the degree of mucin deposition using a 4-point scale.ResultsVarious amounts of mucin deposition were observed in the periadnexal area of patients who were diagnosed with chronic eczema. Mucin deposition was more visible after staining with mucin-specific stains. Evaluation of the staining analysis scores revealed that the staining intensities were significantly higher in patients with chronic eczema than age- and site-matched controls (normal, acute to subacute eczema, and psoriasis vulgaris).ConclusionPeriadnexal mucin (secondary mucinoses) may be an additional finding of chronic eczematous dermatitis.     

Diffuse large cell non-Hodgkin's lymphoma, CD30+, T-cell phenotype

A 63-year-old Chinese man presented with an eczematous dermatitis that progressed into a multifocal nodular eruption. Histopathologic examination demonstrated a nodular and diffuse infiltrate in the reticular dermis, which was composed of lymphocytes, macrophages with granulomatous inflammation, and numerous eosinophils. Reactive lymphoid follicles with germinal centers also were present. Immunohistochemistry showed CD30 and LCA. ALK-1 and CD20 were negative. A diagnosis of CD30+ cutaneous T-cell lymphoma was made, and the patient is currently undergoing staging of his disease. Treatment options include excision of nodules, radiation therapy, and systemic chemotherapy.     

Persistent polymorphous light eruption after ultraviolet A1 phototherapy

Polymorphous light eruption (PMLE) is the most common photodermatosis and is characterized by the development of a pruritic skin eruption within a few hours to days after sun or artificial light exposure. The eruption usually takes up to two weeks to resolve in the absence of further ultraviolet radiation. PMLE has been reported as a side effect of ultraviolet A1 (UVA1) therapy but characteristics of the eruption, especially the duration until resolution after treatment, has not been described. A 37‐year‐old female developed an unusually persistent PMLE that lasted for 5 weeks after completion of UVA1 phototherapy.     

Marked papillary dermal edema – an unreliable discriminator between polymorphous light eruption and lupus erythematosus or dermatomyositis

Background: The clinical differential diagnosis of photo‐distributed papules and plaques includes polymorphous light eruption (PMLE) and lupus erythematosus (LE). These entities share many histopathological features. However, in most contemporary textbooks, a broad band of papillary dermal edema is reported to be characteristic of PMLE and not seen in LE. Nonetheless, older reports describe papillary dermal edema in LE, including acute cutaneous LE (ACLE) in patients with systemic LE (SLE) and early lesions of discoid lupus erythematosus (DLE). Older reports also describe papillary dermal edema in microscopic sections of dermatomyositis (DM). Methods: Retrospective review. Results: Nine cases of LE (including two patients with acute lesions of SLE, six with DLE and one unclassifiable) and three cases of DM were identified in which sections showed striking papillary dermal edema. Attributes of chronicity, such as epidermal atrophy, follicular plugging and basement membrane thickening, were present concurrently in many sections. Conclusions: Marked papillary dermal edema does not reliably distinguish PMLE from LE as it can be seen in ACLE, early and late lesions of DLE and DM. This phenomenon has been underemphasized in recent reports and textbooks. Furthermore, papillary dermal edema in chronic lesions of DLE has not been previously reported. Pincus LB, LeBoit PE, Goddard DS, Cho RJ, McCalmont TH. Marked papillary dermal edema – an unreliable discriminator between polymorphous light eruption and lupus erythematosus or dermatomyositis.     

Polymorphous light eruption in African Americans: pinpoint papular variant

BACKGROUND: Polymorphous light eruption (PMLE) is the most common chronic idiopathic photodermatosis usually manifesting as a papular eruption (3-6 mm), with several other morphological variants described. METHODS: Between June 1998 and August 2001, nine patients presented with complaints of a pruritic pinpoint papular eruption associated with sun exposure. A detailed history and complete skin examination were performed along with a skin biopsy if active lesions were present. Phototesting to ultraviolet-A (UV-A), ultraviolet-B (UV-B) and visible light was performed in four patients. Antinuclear antibody (ANA) testing was performed in three patients. The diagnosis of PMLE was made based on the history, morphology of the lesions, results of phototesting and skin biopsy if available. RESULTS: In all patients, pinpoint papules (1-2 mm) were observed on sun-exposed areas, sparring the face and flexural surfaces. All patients were African American women with skin type IV-VI and a mean age of 39.3 years (range 21-52 years). Phototest results were normal in three patients; one patient, who was on glyburide, had a decreased minimal erythema dose to UV-A. ANA testing was negative. Two histopathologic patterns were observed: (i) focal lichenoid and perivascular lymphohistiocytic infiltrate with red blood cell extravasation in four specimens and (ii) superficial and deep interstitial lymphocytic infiltrate with papillary dermal edema in the remaining three specimens. All patients responded to topical corticosteroids, broad-spectrum sunscreens and antihistamines. CONCLUSION: Recognition of this pinpoint papular variant of PMLE in dark-skinned individuals is important in the evaluation and management of these patients.     

Pinpoint papular variant of polymorphous light eruption: clinical and pathological correlation

BACKGROUND: Polymorphous light eruption (PMLE) is the most common chronic idiopathic photodermatosis usually manifesting as a papular eruption along with several other morphological variants including a pinpoint papular variant. METHODS AND MATERIALS: Between June 1998 and August 2003, 10 PMLE patients presented to the Department of Dermatology at Henry Ford Hospital with complaints of a pruritic pinpoint papular eruption associated with sun exposure. In six patients skin biopsies were performed along with a detailed history and complete skin examination. We correlated the histology with the clinical course of disease corresponding to acute and subacute disease presentation. We also performed immunohistochemistry on three cases to study the immunophenotype in PMLE. RESULTS: The clinical, histologic and immunostain findings are summarized. Acute: Clinically pinpoint papules and vesicles, some with erythematous base, were seen. Histology showed focal vesicle formation, spongiosis, oedema, red blood cells extravasation, and superficial and deep perivascular and interstitial lymphocytic infiltrate with occasional eosinophils. Subacute: Clinically pinpoint papules with or without erythema were seen. Histology of the pinpoint lesion showed a nodular collection of lymphocytes and histiocytes with claw-like extension of epidermal rete ridges at the lateral boundaries of the lesion. Overlying epidermal atrophy with adjacent spongiosis, exocytosis, oedema and a superficial perivascular lymphocytic infiltrate and parakeratosis was also observed. The histologic differential diagnosis included lichen nitidus. Immunohistochemical stains revealed the following results: CD8, CD68 positive, CD4 variable (strongly positive to negative) and S-100 negative. CONCLUSION: (i) Pinpoint papular variant of PMLE is a distinct entity, which shows characteristic histology corresponding to the clinical course of the disease (acute and subacute). (ii) The histologic and immunophenotypic differential diagnosis of this variant during the subacute phase includes lichen nitidus.     

Histopathologic findings in lupus erythematosus tumidus: review of 80 patients

BACKGROUND: In a recent study, we demonstrated that lupus erythematosus (LE) tumidus (LET) is a distinct subset of cutaneous LE (CLE), which is clinically characterized by erythematous, urticaria-like, nonscarring plaques in sun-exposed areas. OBJECTIVE: Our purpose was to analyze skin biopsy specimens from 80 patients with this disease and to determine whether it could be differentiated from other variants of CLE on histopathologic grounds. METHODS: Skin biopsy specimens from 53 primary and 38 UVA- and/or UVB-induced lesions of 80 patients with LET were examined and compared with skin biopsy specimens from patients with discoid LE (DLE) and subacute CLE (SCLE). RESULTS: Specimens from LET lesions showed a characteristic and diagnostic pattern of perivascular and periadnexal cellular infiltrates in the papillary and reticular dermis composed almost entirely of lymphocytes. In some cases, few scattered neutrophils were present. Furthermore, interstitial mucin deposition was observed in all specimens, as confirmed by colloidal iron staining. In contrast to discoid LE and subacute CLE lesions, epidermal atrophy or alteration at the dermoepidermal junction was not detected. CONCLUSION: Skin lesions of patients with LET present with specific histopathologic features, and the differences compared with subacute CLE and discoid LE further support the concept to consider LET as a separate entity of CLE.     

Lupus erythematosus with exclusive involvement of the acrosyringia

Cutaneous lesions of lupus erythematosus (LE) show a broad spectrum of clinicopathologic features. Histopathologically, besides typical patterns such as interface dermatitis, perivascular lymphocytic infiltrate and dermal mucin deposits, an involvement of the eccrine structures, especially the acrosyringium, may be observed. We describe the case of a 21-year-old woman with a 4-year history of systemic LE, who presented with a 'butterfly' rash over the cheeks as well as erythematous macules on the arms and décolleté. Biopsy from one lesion on the arm revealed interface changes, necrotic keratinocytes and exocytosis of lymphocytes restricted only to the regions of the acrosyringia. The epidermis between affected acrosyringia was normal with no hints of interface dermatitis. The eccrine glands and coils were not affected. In the dermis there were only sparse inflammatory infiltrates. Differential diagnoses such as erythema multiforme, drug eruption and lichen planus could be ruled out because of histopathologic features and clinical presentation. This is an example of a peculiar histopathological variant of cutaneous LE, characterized by exclusive involvement of the acrosyringia. The histopathologic features represent a pitfall in the diagnosis and can be correctly interpreted only upon correlation with clinical data.     

Vaginal medications as a cause for varied widespread dermatitides

Widespread dermatitis developed in three women after use of vaginal preparations. Besides allergic contact dermatitis, these cases involved erythema multiforme and a photosensitive eruption. Antigen absorption into the general circulation through the vaginal wall, and its deposition at distant skin sites, appeared to account for the spread of the eruption. This type of eruption is akin to the systemic, eczematous, contact-type dermatitis mediated by a systemically given drug in a primarily cutaneously sensitized person.     

Lymphocytic infiltration of the skin (Jessner–Kanof) but not reticular erythematous mucinosis occasionally represents clinical manifestations of Borrelia-associated pseudolymphoma

Background Lymphocytic infiltration of the skin (LIS) and reticular erythematous mucinosis (REM) are characterized histologically by an inflammatory cutaneous lymphocytic infiltrate similar to the histological appearance of pseudolymphoma. Objectives To re‐evaluate a large cohort of patients with the clinical and/or histological diagnosis or differential diagnosis of LIS and REM and to assess the evidence for infection with Borrelia. Methods Sixty‐nine cases of LIS and 34 cases of REM were retrospectively investigated. Haematoxylin and eosin sections were re‐examined, and histological diagnoses were specified and confirmed by clinicopathological correlation. Evidence for Borrelia infection was assessed by immunohistochemistry and focus‐floating microscopy (FFM). Results LIS appeared to serve as a collective term for two main clinicopathological reaction patterns: (i) (tumid) lupus erythematosus (LE) (32 of 69, 46%) and (ii) pseudolymphoma (31 of 69, 45%). Other diagnoses (five of 69, 7%) included polymorphic light eruption, arthropod bite reaction, spongiotic dermatitis, drug eruption and urticaria. Spirochaetes were detected by FFM in 24 of 31 (77%) cases with a pseudolymphomatous reaction, while all nonpseudolymphomatous reactions were negative. Of the cases initially considered as REM, 21 of 34 (62%) were classified as LE, four of 34 (12%) as pseudolymphoma (three of four positive for Borrelia), and five of 34 (15%) as other diagnoses (folliculitis, morphoea, seborrhoeic dermatitis, prurigo and arthropod bite reaction). The diagnosis of Borrelia‐associated pseudolymphoma was made significantly more often in those cases where LIS was considered as initial differential diagnosis than REM (P < 0·05). Conclusions LIS and REM seem to represent clinicopathological reaction patterns. Our results confirm that, after accurate clinicopathological correlation, most cases of both conditions constitute hidden variants of LE. Furthermore, LIS, in contrast to REM, frequently comprises pseudolymphomatous reactions including borrelial lymphocytoma.     

Profiles of Foxp3+ regulatory T cells in eczematous dermatitis, psoriasis vulgaris and mycosis fungoides

Background It is well known that regulatory T cells (Tregs), identified by their expression of CD4, CD25 and Foxp3, play a crucial role in maintaining peripheral tolerance. Recently, it has been demonstrated that a Treg population resides in normal human skin. However, only a few studies have demonstrated the presence of Foxp3+ Tregs in inflammatory skin disorders. Objectives In this study, we immunohistologically examined the presence of CD4+ CD25+ Foxp3+ Tregs in the lesional skin of psoriasis vulgaris, mycosis fungoides and eczematous dermatitis. Methods We used immunohistochemistry to examine the presence of Foxp3+ Tregs in fixed sections of the lesional skin from 16 patients with psoriasis vulgaris, 17 patients with mycosis fungides and 18 patients with eczematous dermatitis in addition to 10 normal skin samples. Results In normal skin, epidermal and dermal Foxp3+ cells were rare. The psoriasis vulgaris, mycosis fungoides and eczematous dermatitis samples contained substantial numbers of epidermal and dermal CD3+, CD4+ and CD25+ Foxp3+ Tregs. The epidermis contained a higher percentage of CD3+, CD4+ and CD25+ Foxp3+ cells than the dermis. The percentage of Foxp3+ cells among CD3+ or CD4+ cells was significantly lower in eczematous dermatitis than in psoriasis vulgaris or mycosis fungoides, and that of dermal Foxp3+ cells was significantly lower in psoriasis vulgaris than in eczematous dermatitis or mycosis fungoides. Conclusions The lower percentage of epidermal or dermal Foxp3+ cells in eczematous dermatitis or psoriasis vulgaris, respectively, might contribute to their pathogenesis.     

IgA multiple myeloma presenting as an acquired bullous disorder

A 63-year-old man presented with an intensely pruritic vesiculo-bullous eruption on the limbs and was subsequently found to have an IgA kappa multiple myeloma. The eruption clinically and histologically was suggestive of linear IgA disease (LAD), dermatitis herpetiformis (DH), epidermolysis bullosa acquisita (EBA), or bullous lupus erythematosus (LE), with the skin biopsy revealing subepidermal bullae and dermal papillary micro-abscesses. However, direct immunofluorescence showed a unique pattern of diffuse dermal IgA staining. Although chemotherapy produced a dramatic resolution of the lesions, which paralleled the fall in serum IgA paraprotein level, the myeloma later became progressive and the resulting paraprotein increase was accompanied by recurrence of the eruption. We propose that this patient's rash was the presenting manifestation of his multiple myeloma, and was a consequence of transudation of IgA paraprotein into the dermis.     

A Case of Eczematoid Graft‐Versus‐Host Disease

A 13‐year‐old boy underwent allogeneic hematopoietic stem cell transplantation (HSCT) for underlying acute lymphoblastic leukemia and achieved neutrophil engraftment 28 days after HSCT. He developed ichthyosis 6 weeks after HSCT and then keratotic follicular papules, palmoplantar keratoderma, and a seborrheic dermatitis–like eruption 18 weeks after HSCT. From skin biopsies he was diagnosed with eczematoid graft‐versus host disease (GVHD), which showed spongiosis with scattered necrotic keratinocytes. He responded to oral and topical steroids and an increase in cyclosporine dose. Although uncommon, eczematoid GVHD must be considered in children who have undergone HSCT and then develop an atypical eczematous eruption, especially in the absence of a history of atopy.     

Dermatomyositis

A 51-year-old woman presented with weakness in her arms and legs and an eruption on the dorsal aspects of the hands, upper back, and face. Histopathologic features showed vacuolar alteration of the basal layer, a thick basement membrane, and deposits of connective-tissue mucin in the papillary dermis and the upper reticular dermis. Dermatomyositis is an idiopathic disease that is characterized by specific cutaneous manifestations and myopathy, which may be associated with occult malignancy. Treatment options include corticosteroids and other immunosuppressive agents such as methotrexate, cyclosporine, mycophenolate mofetil, and azathioprine.     

Physical properties of the photodamaged human skin dermis: Rougher collagen surface and stiffer/harder mechanical properties

Fragmentation of collagen fibrils and aberrant elastic material (solar elastosis) in the dermal extracellular matrix (ECM) is among the most prominent features of photodamaged human skin. These alterations impair the structural integrity and create a dermal microenvironment prone to skin disorders. The objective of this study was to determine the physical properties (surface roughness, stiffness and hardness) of the dermal ECM in photodamaged and subject‐matched sun‐protected human skin. Skin samples were sectioned and analysed by histology, atomic force microscopy and nanoindentation. Dermal ECM collagen fibrils were more disorganized (ie, rougher surface), and the dermal ECM was stiffer and harder, in photodamaged forearm, compared to sun‐protected underarm skin. Cleavage of collagen fibrils in sun‐protected underarm dermis by recombinant human matrix metalloproteinase‐1 resulted in rougher collagen fibril surface and reduced dermal stiffness and hardness. Degradation of elastotic material in photodamaged skin by treatment with purified neutrophil elastase reduced stiffness and hardness, without altering collagen fibril surface roughness. Additionally, expression of two members of the lysyl oxidase gene family, which insert cross‐links that stiffen and harden collagen fibrils, was elevated in photodamaged forearm dermis. These data elucidate the contributions of fragmented collagen fibrils, solar elastosis and elevated collagen cross‐linking to the physical properties of the dermal ECM in photodamaged human skin. This new knowledge extends current understanding of the impact of photodamage on the dermal ECM microenvironment.     

Halo Dermatitis in Children

Halo dermatitis is a pruritic, eczematous eruption on pigmented nevi and halo nevi in young adults. It may be mistaken for nummular eczema, psoriasis, or fungal skin infection. Awareness of halo dermatitis will possibly reveal more cases in children, which have been reported only rarely.     

Delayed contact allergies in patients with photosensitivity dermatitis

Delayed contact allergies and the clinical course of the skin disease were investigated in 14 patients with photosensitivity dermatitis/actinic reticuloid and 145 patients with polymorphous light eruption type eczema. Hypersensitivity to chromium and rubber chemicals was encountered in photosensitivity dermatitis more often than in polymorphous light eruption eczema and in the comparison series of 1714 patients with other types of dermatitis. In the eczema group, delayed contact allergies to chromium, rubber chemicals, neomycin, clioquinol, balsam of Peru, fragrance and colophonium were more frequent than in the comparison group, suggesting that at least delayed contact allergy to chromium and rubber chemicals may be of significance in the development of photosensitivity in many patients who suffer eczematous reaction to sunlight.