Necrotic Keratinocytes Research Articles

Photodistributed reticulated hyperpigmentation related to diltiazem

Diltiazem is a calcium channel blocking agent used for the treatment of hypertension. Cutaneous adverse effects are uncommon. The most frequently reported are itching, urticaria, and maculopapular eruption. A peculiar, cutaneous photodistributed reticulated hyperpigmentation secondary to diltiazem has been recently reported. A 66-year-old white woman with a 2 year history of pruritic hyperpigmented lesions on her face was seen in the clinic. Past medical history was remarkable for hypertension, which had been treated with diltiazem. Physical examination showed slate-gray to brown reticulated hyperpigmentation in the photo-exposed areas of the face and neck. Histological examination revealed interface dermatitis with liquefactive degeneration of the basal layer, necrotic keratinocytes, lymphocytic inflammatory infiltrate, and melanophages in the superficial dermis. A diagnosis of diltiazem-induced hyperpigmentation was established and diltiazem was stopped. Gradual resolution of the hyperpigmentation was observed over the following months. Although diltiazem has been marketed for over 20 years, the first cases of this particular type of reticulated hyperpigmentation were described in 2001. Since then, to our knowledge, only 17 cases have been reported in the literature. In all cases, cutaneous lesions appeared at least 6 months after this treatment had been started. Hyperpigmentation was controlled by means of photoprotection and discontinuation of diltiazem. Diltiazem can produce a characteristic lichenoid dermatitis with reticulated hyperpigmentation on sun-exposed areas.

Erythema multiforme major due to occupational exposure to the herbicides alachlor and butachlor

Alachlor and butachlor are commonly used chloroacetanilide herbicides. They are cytotoxic, but there have been rare reported cases of alachlor or butachlor induced erythema multiforme major. We report the case of a 38-year-old farmer with erythema multiforme major due to the occupational exposure to alachlor/butachlor. The patient presented to the ED because of itching. Confluent erythematous to violaceous maculopatches with bullae and erosions were seen on the trunk, both upper extremities and both lower extremities. He had no relevant past or family history of a similar skin disease. He had used alachlor/butachlor for 3 days before he developed the itch. We performed a skin incisional biopsy and found diffuse hydropic degeneration with many necrotic keratinocytes in the epidermis and mild to moderate superficial perivascular lymphocytic infiltrate admixed with neutrophils and eosinophils in the upper dermis. These results confirmed the diagnosis of erythema multiforme major. The patient was admitted and received systemic and topical steroids. After 18 days, most lesions had healed, and he was discharged.

La rougeole, une maladie folliculaire

Since the year 2000, measles epidemics have occurred throughout Europe, with a number of severe cases in adults leading to hospitalisation. Herein, we discuss the case of a young adult male with measles presenting clinical and histological features of rash having a follicular nature. An 18-year-old male consulted for diffuse, febrile morbilliform exanthem consisting chiefly of follicular papules surrounded by erythematosus macules. In the absence of any features suggesting possible contagion or implicated medication, biopsy was performed on one of these elements and showed strictly follicular involvement. Perifollicular lymphocytic inflammation was noted, with necrotic keratinocytes having monster nuclear cells, and above all, multinucleated cells within the outer root sheath and the sebaceous gland. Positive IgM measles serology was noted. Follicular involvement is a very common feature in cases of measles that we have seen in recent years. In the present case, histological examination showed a follicular and sebaceous cytopathogenic effect, which while far less well known, has occasionally been seen with measles in the sweat glands or the epidermis, in which viral presence was detected. Thus, the skin rash was accounted for at least in part by the presence of the virus itself within keratinocytes and adnexal cells. This follicular involvement of measles, histologically confirmed in the present case, is frequently seen and can be helpful in differential clinical diagnosis with regard to other viral rashes. It could be caused by special affinity of the virus for body hairs.

Flagellate Dermatitis as a Bleomycin-Specific Adverse Effect of Cytostatic Therapy

In oncology, bleomycin is a frequently used drug for the treatment of several malignancies. In particular, it is part of chemotherapy protocols in testicular cancer. We report on two patients with testicular cancer who received bleomycin-including chemotherapy and developed flagellate dermatitis. This is a typical adverse effect of bleomycin therapy; however, its pathophysiology has not yet been clarified. We discuss possible pathophysiologic mechanisms for this reaction. In general, it has been postulated that histopathologic findings in flagellate dermatitis share similarities with those observed in fixed drug eruptions. In fact, published cases in the literature have shown a broad variety of histologic changes and the histopathologic investigation of our two patients was not indicative of fixed drug eruption-like changes. Histology of one patient showed a superficial and deep, perivascular and periadnexal infiltrate of lymphocytes and eosinophils with a prominent perisudoral distribution, whereas the other patient was remarkable only for the presence of a rather sparse, superficial, perivascular lymphocytic infiltrate with occasional eosinophils and a few melanophages. Epidermal changes, in particular necrotic keratinocytes, were not present in either patient. We provide an overview of all reported histologic changes in bleomycin-induced flagellate dermatitis, including our experience with two patients. Based on these data, we present a summary of the clinical and histologic features.

Histopathological findings in oral lichen planus and their correlation with the clinical manifestations

To highlight the most characteristic histopathological findings of oral lichen planus and their correlation with the clinical manifestations and forms. We performed a retrospective study of 50 biopsied and diagnosed cases of oral lichen planus obtained over a period of 11 years, spanning from May 1998 to April 2009. We analyzed the age and sex of the patient, type of lichen planus, location and different histopathological findings, comparing them with the clinical lesions. Seventy eight percent of the patients are female and 22% are male, with an average age of 56.06 years for both sexes. The most frequent clinical form is reticular, present in 78% of the cases, and the most common location is the buccal mucosa, present in 70% of the patients. Hydropic degeneration of the basal layer and lymphocytic infiltration in the subepithelial layer are observed in the entire sample. Signs of atypia were identified in 4% of the cases, but without dysplasic features. Other common histological findings were the presence of necrotic keratinocytes (92%), hyperplasia (54%), hyperkeratosis (66%), acanthosis (48%), and less frequently, serrated ridges (30%) and the presence plasma cells (26%). Oral lichen planus is a disease that is more common in women, usually appearing in the fifth and sixth decades of life. The most common clinical form is reticular, manifesting mainly in the buccal mucosa. Histological findings characteristic of oral lichen planus include hydropic degeneration of the basal layer, lymphocytic infiltration in the subepithelial layer and the absence of epithelial dysplasia; however, it is also frequent to observe hyperplasia phenomena at the epithelial level, hyperkeratosis, acanthosis and the presence of necrotic keratinocytes.

Development of Bullous Acrodermatitis Enteropathica during the Course of Chemotherapy for Acute Lymphocytic Leukemia

Acrodermatitis enteropathica (AE) is an uncommon autosomal recessive genetic disorder of zinc malabsorption. The acquired form may be associated with inadequate intake, impaired absorption, and increased excretion of zinc. Those afflicted present with diarrhea, stomatitis, psychiatric symptoms, non-scarring alopecia, and nail dystrophy accompanied by erythematous which appears as scaly patches with erosion vesicles and pustules mostly affecting the extremities, perineal, and periorificial areas. Due to the variable findings of most case reports, the clinical and histopathological features of AE are often regarded as non-specific. We report an unusual case of bullous AE secondary to total parenteral nutrition for the treatment of acute pancreatitis occurring in a six-year-old male with acute lymphocytic leukemia who underwent chemotherapy. He presented with periorificial, reddish, eroded bullae with multiple vesicles and blisters on his fingers, toes, and buttock, showing necrotic keratinocytes with multiple intraepidermal vesicles and perivascular infiltration with predominant lymphocytes and few neutrophils within the dermis. To the best of our knowledge, this is the first case report of bullous AE in the Korean dermatologic literature.

Purpuric macules with vesiculobullous lesions: a novel manifestation of Chikungunya

Chikungunya (CHIK) is an emerging viral disease with a myriad of cutaneous manifestations. The aim of our study was to document the morphology and evolution of skin lesions in cases presenting with fever, purpuric macules and vesiculobullous lesions, to confirm its causative relationship with CHIK, and to investigate further in order to delineate possible mechanisms of bulla formation in these cases. A prospective, descriptive hospital-based study was carried out at a tertiary health care centre in Kerala. A total of 10 patients were enrolled in the study and investigated. All cases had morbilliform eruption prior to onset of purpuric macules. Eight cases developed vesiculobullous lesions that arose either de novo or over a part or whole of the purpuric macules. Skin lesions resolved within an average of 7.6 days leaving post-inflammatory hypopigmentation. IgM CHIK enzyme-linked immunosorbent assay (ELISA) was positive in all 10 patients. Tzanck smear from the bullae showed lymphocytes in most cases along with acantholytic cells, necrotic keratinocytes or occasional neutrophils. Skin biopsy showed intraepidermal or subepidermal bullae. Immunohistochemistry revealed predominantly CD8 positive T lymphocytes in the infiltrate. The prognosis was good with supportive management alone. The clinical features in our cases are comparable to the 3 previous reports of vesiculobullous lesions in CHIK affected infants. Based on the current evidence, we hypothesize that at least 2 mechanisms are at play for these skin lesions; CHIK virus induced keratinocyte necrosis followed by a cytotoxic immune response, and possible modulation of rash by drugs. With severe epidemics of CHIK spreading from Asia and Africa to the Western hemisphere, we must consider bullous CHIK as a differential diagnosis in cases with fever and purpuric and vesiculobullous lesions.

The spectrum of histopathological features in acute generalized exanthematous pustulosis: a study of 102 cases

Acute generalized exanthematous pustulosis (AGEP) is a rare severe pustular reaction pattern with a typical clinical picture. To characterize the histopathological features of AGEP in a large series of cases with a validated diagnosis. METHODS; A multinational retrospective histopathological study was conducted. It included 102 hospitalized patients (recruited within the EuroSCAR and RegiSCAR studies) with a validated diagnosis of probable or definite AGEP. A systematic description of the histopathological features in AGEP was done based on a standardized grading system. Sub/intracorneal pustules (41%), intraepidermal pustules (20%) or combinations of them (38%) were observed in 102 cases. The pustules were usually large (> 15 keratinocytes) (82% and 89%, respectively) and regularly contained eosinophils (36% and 32%, respectively). Spongiform features were less prominent in the sub/intracorneal pustules compared with the intraepidermal pustules (44% and 95%, respectively). The main epidermal features were necrotic keratinocytes (67%), including incidental segmental necrosis (7%), and spongiosis (80%) with neutrophil exocytosis (77%). The main dermal features were papillary oedema (88%) and mixed superficial (100%), interstitial (93%), and mid/deep-dermal infiltrates (95%) containing neutrophils (100%) and eosinophils (81%). Follicular pustules were also seen (23%), but vasculitis generally was absent. Classical features of plaque-type psoriasis were infrequent and usually mild. No significant differences were observed between a subgroup of 16 cases with and 86 cases without psoriasis. The present histopathological study concerns a large series of cases with a validated diagnosis of AGEP. It provides diagnostic clues in favour of AGEP in patients with a pustular eruption.

The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis

Acute generalized exanthematous pustulosis (AGEP) represents a severe, acute, pustular skin reaction that is most often induced by drugs. AGEP can be difficult to differentiate from generalized pustular psoriasis (GPP) both clinically and histopathologically. We present a systematic description of the histopathological spectrum of AGEP and GPP with a focus on discriminating features. A retrospective, descriptive, comparative histopathological study was completed utilizing step sections of 43 biopsies of 29 cases with a validated diagnosis of probable or definite AGEP and 24 biopsies of 19 cases with an established diagnosis of GPP. In AGEP, biopsies from erythema and pustules showed minor differences, whereas histopathology of the acute stage of GPP showed major differences compared to the chronic stage. Comparing AGEP and GPP, the presence of eosinophils, necrotic keratinocytes, a mixed interstitial and mid-dermal perivascular infiltrate and absence of tortuous or dilated blood vessels were in favor of AGEP. Moreover, chronic GPP was characterized by prominent epidermal psoriatic changes. The frequency of a psoriatic background of AGEP patients in our study was higher than that of psoriasis in the general population. However, histopathology of a subgroup of AGEP patients with a personal history of psoriasis revealed no significant differences from the other AGEP patients. The spectrum of histopathological features of both AGEP and GPP is presented. Despite considerable overlap, subtle consistent histopathological differences and the grade of severity of specific features can help in differentiation. We could neither substantiate earlier reports that follicular pustules exclude AGEP nor did we see vasculitis as a specific feature in AGEP. Our study also supports the concept that AGEP is a separate entity that is distinct from GPP.

Pigmented contact dermatitis due to therapeutic sensitizer as complication of contact immunotherapy in alopecia areata

Pigmentary complication by contact immunotherapy (CI) for alopecia areata (AA) has been reported but its pathophysiology remains unknown. To characterize pigmentary complication by CI and its pathophysiology, we examined the incidence of hyperpigmentation in 186 consecutive patients treated with CI using diphenylcyclopropenone. From clinical data of AA totalis (AAT) or universalis (AAU) patients (n = 78), we studied the correlations between this complication and age, sex, atopic background, duration and treatment responsiveness, duration of CI, final concentration of diphenylcyclopropenone and administration of anti-histamines by χ(2)-test or Mann-Whitney U-test. Additionally, the histopathology of pigmentation was studied. As a result, 11 (5.91%) of the 186 patients had hyperpigmentation in this series. All of them had AAT or AAU, suggesting that the pigmentation is apt to occur in severe AA. When the AAT or AAU patients with (n = 11) and without hyperpigmentation (n = 67) were compared, those with pigmentation showed poorer responsiveness to CI (P < 0.05) but no significant tendency for other factors. Histopathologically, skin specimens showed lichenoid or vacuolar interface dermatitis with necrotic keratinocytes and dermal melanophages, consistent with pigmented contact dermatitis (PCD). Together, pigmentary complication by CI corresponds to PCD from therapeutic sensitizer, representing clinical indicator of poor responsiveness.

TLR4-mediated skin carcinogenesis is dependent on immune and radioresistant cells

Skin cancers are the most commonly diagnosed cancers. Understanding what are the factors contributing to skin tumour development can be instrumental to identify preventive therapies. The myeloid differentiation primary response gene (MyD)88, the downstream adaptor protein of most Toll-like receptors (TLR), has been shown to be involved in several mouse tumourigenesis models. We show here that TLR4, but not TLR2 or TLR9, is upstream of MyD88 in skin tumourigenesis. TLR4 triggering is not dependent on lipopolysaccharide associated to skin-colonizing bacteria, but on the high mobility group box-1 protein (HMGB1), an endogenous ligand of TLR4. HMGB1 is released by necrotic keratinocytes and is required for the recruitment of inflammatory cells and for the initiation of inflammation. The expression of TLR4 on both bone marrow-derived and radioresistant cells is necessary for carcinogenesis. Consistently, a human tissue microarray analysis showed that melanoma and colon cancer display an over-expression of TLR4 and its downstream adaptor protein MyD88 within tumours. Together, our results suggest that the initial release of HMGB1 triggers a TLR4-dependent inflammatory response that leads to tumour development.

Index Of Suspicion In The Nursery

A 2.9-kg female infant is born at 35 weeks' gestation to a 33-year-old G4P3 woman via cesarean section due to chronic hypertension complicated by superimposed preeclampsia. The mother's blood type is A-negative; the antibody screen is positive for anti-D, anti-C, and anti-G antibodies; she has no prior history of sensitization; and her serologies are negative. The Apgar scores are 7 and 9 at 1 and 5 minutes, respectively. At birth, the infant appears pale and exhibits tachycardia, moderate hepatosplenomegaly, tachypnea, and mild respiratory distress requiring supplemental oxygen. Complete blood count and blood cultures are obtained, and ampicillin and gentamicin are started. The admission hematocrit is 21% (0.21), with a reticulocyte count of 64%. An umbilical venous catheter is placed for intravenous (IV) access. The infant receives a transfusion of packed red blood cells for significant anemia associated with tachycardia. Prophylactic phototherapy is started because of Rh sensitization. The cord blood bilirubin measures 11.4 mg/dL (195 mcmol/L). The infant's blood type is A-negative, and the antibody screen is positive for anti-D and anti-C antibodies, with a positive direct Coombs test. The red blood cell phenotype reveals the presence of “C” antigen. This is a very uncommon antigen in an Rh-negative infant, but the antigen had stimulated the anti-C antibodies that traversed the placenta and caused severe hemolysis of the newborn. At 7 hours of age, the infant's bilirubin is 16 mg/dL (273.6 mcmol/L). She is given two doses of intravenous immune globulin, and phototherapy is intensified. After 24 hours of intensive phototherapy, the infant develops a large reddish-purple discoloration on her abdomen that resembles a severe burn (Fig. 1). The well-demarcated, erythematous, purpuric rash is present over the areas closely exposed to the phototherapy lights and does not blanch with diascopy. No vesiculobullous eruptions, edema, or tenderness is noted. The unexposed …

The cutaneous lesions of Kikuchi's disease: a comprehensive analysis of 16 cases based on the clinicopathologic, immunohistochemical, and immunofluorescence studies with an emphasis on the differential diagnosis

Kikuchi's disease is a self-limited necrotizing lymphadenitis that is characterized by cervical lymphadenopathy and fever. Although it has been reported that some patients with Kikuchi's disease have cutaneous manifestations, the specific skin changes of patients with Kikuchi's disease have not been fully described. We report here on 16 patients of Kikuchi's disease with cutaneous manifestations. We reviewed the clinical histories of the patients who underwent lymph node and skin biopsies. Immunohistochemistry, immunofluorescence, and Epstein-Barr virus-encoded RNA (EBER) in situ hybridization were performed. The patients ranged in age from 7 to 39 years and included 4 males and 12 females. All the patients had histiocytic necrotizing lymphadenitis. The clinical impression was variable according to the various cutaneous manifestations. The skin biopsies showed vacuolar interface changes (12/16; 75.0%), necrotic keratinocytes (11/16; 68.8%), superficial (16/16; 100.0%) and deep (9/16; 56.3%) lymphohistiocytic infiltration, karyorrhexis (16/16; 100.0%), deposition of mucin (5/16; 31.3%), and panniculitis (9/15; 60.0%). Based on immunohistochemistry, the infiltrating cells were predominantly CD68 and CD163-positive histiocytes and CD3-positive T lymphocytes. Of the 16 patients, 13 (81.3%) had a slight predominance of CD8-positive lymphocytes. Direct immunofluorescence staining and EBER in situ hybridization were all negative. Although the clinical and histopathologic findings are very heterogenous, the presence of a lymphohistiocytic infiltration with nonneutrophilic karyorrhexis helps to make the diagnosis of Kikuchi's disease with skin involvement.

Paraneoplastic pemphigus

Paraneoplastic pemphigus (PNP) is a life-threatening autoimmune mucocutaneous blistering disease associated with malignancy, particularly lymphoproliferative neoplasms. Clinically, it is characterized by severe and intractable mucositis and polymorphous cutaneous eruptions, ranging from blisters to lichenoid lesions. The histologic features are also diverse according to the morphology of the clinical lesions, ranging from suprabasal acantholysis to interface changes with necrotic keratinocytes. PNP is characterized by the production of autoantibodies against the plakin family proteins as well as the desmoglein 1 and 3, which are target antigens of ordinary pemphigus. Thus, indirect immunofluorescence on substrates other than skin is useful in the diagnosis of PNP. The presence of anti-desmoglein antibodies have been demonstrated by enzyme-linked immunosorbent assay. The gold standard for the diagnosis of PNP however, is the detection of the characteristic circulating autoantibodies against 210-kDa envoplakin and 190-kDa periplakin by immunoblotting or immunoprecipitation. It is now accepted that both humoral and cellular immunities are involved in the pathogenesis of PNP. Anti-desmoglein 3 antibodies are known to play a pathogenic role in the initiation of acantholytic blister formation. Autoreactive CD8 + cytotoxic T cells induced by antitumor immune response are also involved in the development of mucocutaneous manifestations and bronchiolotis obliterans. The prognosis of PNP depends on the nature of the underlying neoplasm, with high mortality rate due to sepsis or multi-organ failure, particularly bronchiolitis obliterans. Although the combined use of immunosup-pressive agents and rituximab has been administered in treating PNP, to date, there are no consistently effective treatments for PNP.

Perniosis: Clinical and Histopathological Analysis

Perniosis are inflammatory cutaneous lesions, located on acral skin, which present in association with cold exposure. They can appear as an idiopathic dermatosis or with an underlying autoimmune disease. The use of cutaneous biopsy to distinguish between both types is controversial. We analyze the histological findings in 9 cases of idiopathic perniosis (IP) and compare them with those obtained from 11 cases of perniosis associated with an autoimmune disease (autoimmune perniosis). The most frequent histopathological features observed in cases of IP were a lymphocytic infiltrate with perivascular (8 cases, 89%) and perieccrine distribution (6 cases, 66%), dermal edema (5 cases, 55%), and necrotic keratinocytes (5 cases, 55%), whereas those found in perniosis associated with an autoimmune disease were lymphocytic infiltrate with perivascular distribution (11 cases, 100%) but without perieccrine distribution (3 cases, 27%), vacuolation of the basal layer (7 cases, 63%), and necrotic keratinocytes (5 cases, 45%). The only significant difference between both groups was the perieccrine distribution of the lymphocytic infiltrate in cases of IP, which, as mentioned in previous studies, could be considered a histopathological clue to differentiate both types of perniosis.

Clinical, Etiologic, and Histopathologic Features of Stevens-Johnson Syndrome During an 8-Year Period at Mayo Clinic

To examine clinical, etiologic, and histologic features of Stevens-Johnson syndrome and to identify possible correlates of clinical disease severity related to etiologic and histopathologic findings. This is a retrospective review of patients seen at Mayo Clinic between January 1, 2000, and December 31, 2007. Of 27 patients (mean age, 28.1 years), 22 (81%) had involvement of 2 or more mucous membranes, and 19 (70%) had ocular involvement. Medications, most commonly antibiotics and anticonvulsants, were causative in 20 patients. Mycoplasma pneumoniae infection caused 6 of the 27 cases. Corticosteroids were the most common systemic therapy. No patients with mycoplasma-induced Stevens-Johnson syndrome had internal organ involvement or required treatment in the intensive care unit, in contrast to 4 patients each in the drug-induced group. Three patients had chronic ocular sequelae, and 1 died of complications. Biopsy specimens from 13 patients (48%) showed epidermal necrosis (8 patients), basal vacuolar change (10 patients), and subepidermal bullae (10 patients). Biopsy specimens from 11 patients displayed moderate or dense dermal infiltrate. Histologic features in drug-induced cases included individual necrotic keratinocytes, dense dermal infiltrate, red blood cell extravasation, pigment incontinence, parakeratosis, and substantial eosinophils or neutrophils. Our clinical and etiologic findings corroborate those in previous reports. M pneumoniae-induced Stevens-Johnson syndrome manifested less severely than its drug-induced counterpart. The limited number of biopsies precludes unequivocal demonstration of histopathologic differences between drug-induced and M pneumoniae-induced Stevens-Johnson syndrome.

Histiocytic erythema multiforme

Erythema multiforme is histologically characterized by liquefactive degeneration along the dermal-epidermal junction, necrotic keratinocytes and a lymphocytic infiltrate. We report a 10-year-old boy with recurrent erythema multiforme major of undetermined etiology with unusual histologic findings. A skin biopsy taken at day 2 of his eruption revealed histologic features otherwise characteristic of erythema multiforme, but mediated instead by a CD68-positive infiltrate, resembling cutaneous Kikuchi's disease. To the best of our knowledge this is the first reported case of 'histiocytic' erythema multiforme.

Pregnancy-Associated Dermatomyositis

Dermatomyositis (DM) is an idiopathic inflammatory myopathy with characteristic skin manifestations. Reports of the association between DM and pregnancy are rare, though two types of pregnancy-related DM have been proposed: one presenting during pregnancy and the other less common type developing postpartum.1 Three reported cases of the latter exist including a 33-year-old woman who manifested symptoms of classic DM (CDM) five days after her first delivery, a 29-year-old woman who developed DM one month after a normal delivery and a woman who was diagnosed fifteen days after a cesarean section.1,2,3 In addition, two cases describe postpartum exacerbation in which a 31-year-old woman who experienced periungual erythema at 32 weeks gestation developed full-blown CDM three months after delivery and another woman who suffered a flare of her childhood DM during the post-spontaneous abortion period.3,4 Various triggers for pregnancy-associated DM may include exposure of the mother to fetal antigens and maternal hormonal changes.1 We report a patient with amyopathic DM (ADM) that developed after a spontaneous abortion and progressed two years later to CDM after the delivery of a healthy infant. A 38-year-old woman was diagnosed with ADM based on clinically and histologically typical skin findings beginning four days after a spontaneous abortion. Physical examination revealed forehead and malar erythema with scale, gottron's papules over the bony prominences of her hands and elbows and mild cuticular telangiectasias. A skin biopsy was compatible with DM (Fig 1). She denied any muscle weakness or dysphagia. Further testing revealed negative antinuclear and anti-Jo1 antibodies, normal aldolase and creatine kinase (CK) levels, as well as normal electromyography (EMG) and pulmonary function testing (PFT). A malignancy work-up was unremarkable. A three-week course of oral prednisone significantly improved her inflammatory skin findings and hydroxychloroquine stabilized her disease activity. Figure 1 Skin biopsy of right middle finger, demonstrating an interface dermatitis, characterized by a patchy band-like lymphocytic infiltrate in the superficial dermis, basal vacuolar alteration of the epidermis and necrotic keratinocytes. (Hematoxylin-eosin ... Seven months later, the patient achieved pregnancy with in vitro fertilization. Her ADM remained stable throughout this period. However, four months after a normal delivery, the patient's skin gradually worsened and she developed pruritic erythematous plaques on her face, v-neck erythema and gottron's papules on her hands and elbows (Fig 2). After three months, she also experienced difficulty climbing stairs and lifting her daughter. Muscle enzymes were elevated with a CK level of 8,241 U/L (ref ≤ 165) and aldolase level of 53.6 U/L (ref ≤ 8.1) and an EMG confirmed the presence of myositis. Treatment with high-dose prednisone and azathioprine improved her muscle weakness and normalized her enzymes after two months. Figure 2 Gottron's papules on the knuckles (A) and elbow (B). Of note, the patient started the first of two cycles with clomiphene citrate the day her rash first appeared. In hope of a second pregnancy, she received one more treatment a month prior to her muscle flare. Ovarian hyperstimulation following six to ten cycles of therapy has been associated with the induction or exacerbation of systemic lupus erythematosus in women5. The timing and number of cycles make clomiphene a less likely trigger of DM in this case. However, hormonal fluctuations potentially play an important role in the pathogenesis of DM.

Erythema multiforme-like contact reaction due to liquid-formulated 2,2-dibromo-3-nitrilopropionamide: involvement of cytotoxic T-lymphocyte reaction

Erythema multiforme (EM)-like contact reactions are induced by exposure to various chemicals. We report two industrial workers from a paper mill who presented with generalized EM-like lesions 17 and 10 days, respectively, after accidental exposure to liquid-formulated 2,2-dibromo-3-nitrilopropionamide (DBNPA) 20%. The EM-like lesions appeared as subepidermal blisters associated with many necrotic or apoptotic keratinocytes and dense lymphocytic infiltration in the epidermis. Most of the infiltrating cells in the epidermis were CD8-positive T lymphocytes expressing cytotoxic molecules, including T cell-restricted intracellular antigen (TIA)-1, granzyme B and granulysin. Steroid pulse therapy failed to suppress the development of the lesions sufficiently, but cyclosporin 2.5-3 mg/kg successfully controlled the disease. DBNPA-induced, generalized EM-like eruptions may be mediated by cytotoxic T-lymphocytes.

Isomorphic cutaneous graft‐versus‐host disease reaction after ultraviolet exposure: clinical, histological and direct immunofluorescence studies of four allo‐transplanted patients

Acute and chronic graft-versus-host disease (GVHD) continues to be a major limitation to successful haematopoietic stem cell transplantation. If experimental studies and clinical observations could partially elucidate the pathophysiology of acute GVHD, the biology of chronic GVHD is still much less well understood. The aim of this study is to describe a peculiar photoinduced rash which triggered acute and then chronic lesions of GVHD in four allogenic haematopoietic-transplanted patients and discuss the possible aetiology and treatment. Four patients, two children and two adults affected by either mild or severe chronic GVHD, developed an erythematous rash on sun- or narrow-band ultraviolet B-exposed area, which triggered the onset of acute lesions of GVHD. Any of the patients presented neither a history of photosensitivity nor circulating autoantibodies nor urinary/fecal porphyrine. The histopathologic findings were characterized by an interface dermatitis with sparse perivascular infiltrate of lymphocytes and scattered necrotic keratinocytes, especially in the upper part of epidermis. Direct immunofluorescence studies excluded lupus-like pattern, revealing nests of fluorescent bodies at the dermal-epidermal junction and in papillary dermis. This peculiar isomorphic reaction of cutaneous GVHD after sun or narrow-band ultraviolet B exposures is described, and the possible mechanism involved is discussed. It may represent an interesting model of progression of chronic GVHD, starting with an acute stage and ending up with chronic clinical and histological findings, especially considering that there is no animal model that fully replicates all of the features of chronic GVHD in humans.