Dermal Edema Research Articles

DRESS syndrome following ciprofloxacin exposure: An unusual association

Patient: Female, 24Final Diagnosis: DRESS syndromeSymptoms: Fever • rash • facial and body swelling • muscular pain • diarrheaMedication: CiprofloxacinClinical Procedure: —Specialty: Internal Medicine • HematologyObjective:Unusual or unexpected effect of treatmentBackground:Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a rare, potentially life-threatening drug reaction with a mean latency period of 3.9 weeks. It has been described in association with many medications; yet, Ciprofloxacin was reported once in literature to be the offending drug. We are presenting a rare case of Ciprofloxacin-induced DRESS syndrome with symptom onset 2 days after exposure.Case Report:A 24-year-old female presented with symptoms suggestive of UTI and was prescribed Ciprofloxacin. Two days later she started to complain of fever, diffuse rash, swelling of her face, arms and flanks, watery diarrhea and muscular pain. Five days after symptom onset she presented to our institution with WBC count 38,810 cells/μL and absolute Eosinophil count 17,080 cell/μL. Peripheral blood smear showed immature Eosinophilic myelocytes and metamyelocytes. Skin biopsy showed superficial perivascular lymphocytic infiltration with dermal edema. Further workup was negative for parasitic infestations, HIV and viral hepatitis, allergic diseases, hematologic and non-hematologic malignancies, vasculitides and autoimmune processes. Ciprofloxacin was discontinued upon admission and the patient started to improve quickly. Patient was followed in clinic after 3 weeks and was completely asymptomatic with WBC count 7,250 cell/μL and absolute Eosinophil count 2,900 cell/μL.Conclusions:DRESS syndrome is a possible complication of Ciprofloxacin treatment that clinicians should consider. Shorter latency period might be a unique feature of Fluoroquinolone-induced DRESS syndrome. According to RegiSCAR scoring system, our case is categorized as (probable) with a score of (4). In fact, the vast majority of reported cases are classified as (probable/definite).

Morbihan syndrome

We report a case of severe Morbihan syndrome (chronic erythematous edema of the upper portion of the face) in a 60-year-old man. The syndrome was characterized clinically by erythematous edema involving the forehead, glabella, and both eyelids, because of which the patient was not able to open completely his eyes. Furthermore, erythema and telangiectasiae were visible on the nose and cheeks. Laboratory and instrumental examinations were within normal ranges or negative. Histopathological examination showed dermal edema, perivascular and periadnexal lympho-histiocytic infiltrate, and sebaceous gland hyperplasia. Oral isotretinoin was ineffective despite the relatively long duration of the therapy (26 weeks).

Étude histologique et immunohistochimique des anomalies vasculaires et inflammatoires de la rosacée

Rosacea has a number of pathophysiological components, chief of which are vascular abnormalities and inflammation. The morphology of the dilated vessels in rosacea may indicate an increase in the number and size of lymphatic vessels. We carried out a histological and an immunohistological study to quantify these abnormalities in rosacea and compared them with those seen in lupus erythematosus. We reviewed all cases of rosacea analysed over a 4-year period. Ultimately, we only included 86 cases in which the diagnosis could be confirmed by a dermatologist based upon histopathological correlation and follow-up. All biopsies were reviewed for histopathological features, and 25 of these were compared with 25 facial biopsies in documented cases of lupus erythematosus, using standard staining followed by immunohistochemical analysis with anti-CD3, CD4, CD8 and CD20 (lymphocytic) antibodies, anti-CD68 (histiocytic) antibodies, anti-CD31 (endothelial cell) antibodies and anti-D2-40 (podoplanin, a marker for lymphatic endothelial cells) antibodies. In 88% of cases of rosacea, large superficial dermal vessels of geometrical or bizarre configuration were noted, and turgescent cells and dermal edema were frequently seen. Over 75% of cases involved Demodex, including erythemato-telangiectatic subtypes. The rosacea included a mean 15 vessels/mm(2), eight of which expressed D2-40; six were greater than 30μm in diameter (mean: 103μm; maximum: 400μm), with only two of these being D2-40+. The lupus erythematosus biopsies exhibited a mean 15 vessels/mm(2), nine of which expressed D2-40; four measured over 30μm in diameter (mean: 59μm; maximum: 100μm), of which two were D2-40+. The vessels measuring over 100μm were only seen in rosacea, and notable actinic elastosis was associated in 80% of these cases. No Demodex was seen in the lupus cases. The lymphocytic infiltration consisted mainly of CD4+ T cells in both groups, but was chiefly sub-epidermal in lupus, occasionally masking the small vessels of the superficial dermis. Rosacea is characterised by large, dilated, anfractuous capillaries, which are both larger and more numerous than in lupus, although there is no difference in dermal vascular density between the two diseases. Contrary to what their form may suggest, these dilated vessels are not lymphatic. D2-40+ vessels (lymphatic), which are flatter, are found in both lupus and rosacea. The association of large telangiectasias with actinic elastosis may indicate a causative role of exposure to UV radiation. These vessels likely exhibit increased permeability, resulting in dermal edema. Inflammation is consistently present, even in the early forms, strongly suggesting a dual inflammatory and vascular mechanism.

Sweet's syndrome with subcutaneous involvement associated with pegfilgrastim treatment: first reported case

Neutrophilic panniculitis is an infrequent entity, considered by most authors as part of the 'neutrophilic dermatosis' spectrum. Few cases have been reported to be related with granulocyte colony-stimulating factor (G-CSF); we report a case of neutrophilic panniculitis and Sweet's syndrome lesions related with pegfilgrastim, a long-acting G-CSF. A 77-year-old woman with M2 acute myeloid leukemia was treated with chemotherapy as well as broad-spectrum antibiotics and antifungal drugs because of febrile neutropenia. Ten days after a single dose of pegfilgrastim, she developed a limited number of purple plaques on the neck, left leg, both arms and several indurated and slightly mobile nodules on her forearms. Skin biopsy of a plaque showed a diffused dermal neutrophilic infiltrate with dermal edema. Biopsy of a nodule showed a lobular neutrophilic panniculitis without vasculitis. No foreign material was found in those biopsies. No organisms were detected in blood, urine or tissue cultures. She was started with prednisolone 40 mg once a day, with dramatic improvement within the next 2 days. This case is noteworthy for the simultaneous appearance of Sweet's syndrome and neutrophilic panniculitis and it is the first case of neutrophilic panniculitis associated with this drug, pegfilgrastim.

Dermal and ocular irritation and skin sensitization studies of fullerene C60 nanoparticles

Context: Widespread production and use of nanomaterials have caused the release of increasing amounts of nanomaterials into the environment. The introduction of novel materials into industry requires safety evaluations as well as an understanding of the impact of the nanomaterials on human health, because the unique properties and size of nanomaterials may also result in unique health risks. Skin and eyes have the highest risk of exposure to nanomaterials, because deposition to the superficial organs has the potential to be a major route of exposure during the manufacturing, use, and disposal of nanomaterials. However, information on the dermal and eye irritation and sensitization of fullerene C60 nanoparticles is still lacking.Objectives: This study was performed to examine the potential irritating and sensitizing effects of fullerenes on the skin and eyes.Methods: The dermal and eye irritation study was performed using rabbits according to the Organisation for Economic Co-operation and Development (OECD) Guidelines 404 and 405, respectively. The skin sensitization study was carried out in accordance to the OECD Guideline 406 using guinea pigs. The concentrations of the fullerenes in the test substances were the maximum allowable for administration. Fullerenes were applied at 50 mg in dermal irritation, 40 mg in skin sensitization, and 100 mg in eye irritation studies.Results: No dermal responses, including erythema/eschar or edema, were found in rabbits treated with fullerenes. No rabbits exhibited corneal opacity, abnormality of the iris, or chemosis eye at any time point after the application of fullerenes. Fullerenes caused conjunctival redness and blood vessel hyperemia at 1 h, but not at 24 h. No erythema or edema was observed after the challenge with fullerenes in the fullerene-treated guinea pigs.Conclusion: Reversible minimal potential for acute irritation of the eyes was induced by fullerenes, but neither irritation nor sensitization was caused on the skin. Although the present study provided initial information on the acute irritation and acute sensitization of highly purified C60 fullerenes, information on the toxicological effects of fullerenes and their derivatives is still limited. Further information is needed to clarify the potential for toxicity given the complex nature of fullerenes and their derivatives.

Avian Simuliotoxicosis: Outbreak in Louisiana

From April 20 to May 10, 2010, multiple species of birds were seen at the Louisiana State University (LSU) Zoological Medicine Department for a disease syndrome characterized by acute lethargy, generalized subcutaneous petechiae, vasculitis, and death caused by a black fly identified as Simulium meridionale. Twenty psittacine birds presented with severe depression and multifocal subcutaneous hemorrhages over the body and especially noted in the featherless areas of the head and neck. Ten out of 20 clinical cases seen survived on a treatment regimen consisting of intravenous fluid therapy, anti-inflammatories, antihistaminic medications, and supportive care. The 10 other birds likely died of cardiopulmonary collapse and anaphylactoid reactions. In all post mortem examinations multifocal to coalescing dermal hemorrhage, eosinophilic dermatitis, severe edema, and vasculitis were observed. The LSU School of Animal Science conducted a brief survey that included 34 of the 64 Louisiana parishes and showed that 17 parishes, at least, were affected by this outbreak. A total of at least 225 poultry bird deaths could be attributed to black fly strikes. Simuliotoxicosis outbreaks have previously been reported in North America, and this report documents the clinical and post mortem findings, treatment response, and extent of such an outbreak in pet and farm birds in Louisiana.

Treatment of Recalcitrant Eosinophilic Cellulitis With Adalimumab

Eosinophilic cellulitis is a rare condition characterized by recurrent pruritic or tender skin lesions. Biopsies usually display characteristic histologic features of dermal edema, eosinophils, and flame figures (collections of degranulated eosinophilic material). Eosinophilic cellulitis typically responds well to systemic steroids. However, oral steroids may be contraindicated in some patients. In addition, long-term use of systemic steroids can lead to steroid dependence as well as adverse effects on bone density, wound healing, and metabolism. Recent evidence in mice suggests that the tumor necrosis factor (TNF) pathway may play a role in antigen-specific IgE production and eosinophil recruitment. This suggests that TNF inhibitors may have some efficacy in the treatment of eosinophilic cellulitis.

A case of Langerhans cell histiocytosis following acute basophilic leukemia

Dear Editor, Langerhans cell histiocytosis (LCH) is a class of histiocytic cell neoplasm with a clonal neoplastic proliferation of Langerhans-type cells that express CD1a, langerin, and S100 protein and show evidence of Birbeck granules by ultrastructural examination [1]. Concurrent LCH and malignancy have been reported occasionally. LCH occurred before or after malignancies including acute lymphoblastic leukemia, acute myeloid leukemia, and several solid tumors such as malignant lymphoma, retinoblastoma, lung carcinoma, ependymoma, hepatocellular carcinoma, Askin tumor, etc. [2–5]. We present the case of a 38-year-old patient who was diagnosed with LCH following acute basophilic leukemia (ABL). A 38-year-old male presented to the emergency department with a 2-month history of indigestion, nausea, and easy fatigue. Complete blood count with differential showed a white blood cell count of 13,500/μL with 13 % blasts and 14 % basophils, 8.4 g/dL hemoglobin, and a platelet count of 110,000/μL. Hepatosplenomegaly and multiple lymphadenopathies were noted. Bone marrow (BM) aspirates showed 15.6 % leukemic blasts and 11.6 % basophils. Since marked dilution of BM aspirate specimens, the proportion of blasts and basophiles were inaccurate. However, the BM cellularity was approximately 100 % with leukemic blasts. The blasts were of medium-to-large size, had round or cleaved nuclei, contained one or two nucleoli, and a had small amount of bluish cytoplasm. Some blasts had basophilic granules (Fig. 1). Flow cytometric analysis confirmed the presence of the surface markers CD34, CD13, CD33, CD117, and CD65. The blasts showed negative reaction for myeloperoxidase, periodic acid stain, and nonspecific esterase but metachromatic positivity after staining with toluidine blue. Electron microscopy confirmed the presence of basophilic granules in blasts (Fig. 1). The karyotype analysis demonstrated trisomy 16 (47,XY,+16[3]/46,XY[17]). The patient was diagnosed with ABL and received induction chemotherapy. Three months after induction chemotherapy, multiple erythematous indurated patches were observed on the left lower abdomen. Skin biopsy showed evidence of diffuse neutrophilic infiltration with papillary dermal edema and eczematous lesions, without evidence of cancer or fungal infection. Follow-up of BM studies revealed a normocellular marrow with 4.0 % blasts. However, marked increase of histiocytic cells, including immature forms, was noted. The histiocytic cells were clustered in a nodular pattern on the BM clot section. They were of medium-to-large size, with grooved or lobulated nuclei, inconspicuous nucleoli, and moderate amount of homogeneous pinkish cytoplasm. The histiocytic cells were positive for CD1a, S100, and CD68 marker proteins by immunohistochemistry staining (Fig. 2). Based on the morphology and immunohistochemical staining profiles, the patient was diagnosed with BM involvement of LCH. However, a primary lesion of LCH was not found. The patient underwent haploidentical BM transplantation; however, his clinical course continued to deteriorate with systemic fungal infection, necrotizing pneumonia, and hemodynamic instability. Despite aggressive treatment, the patient expired 7 months after diagnosis of ABL. T.-D. Jeong : S. Jang (*) :C.-J. Park :H.-S. Chi Department of Laboratory Medicine, College of Medicine, University of Ulsan and Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, South Korea e-mail: ssjang@amc.seoul.kr

The histology of peau d’orange in breast cancer – what are the implications for surgery?

Surgery is sometimes performed on patients with peau d'orange (dermal oedema) of the breast. This may be done to achieve local control of cancer after neo-adjuvant chemotherapy or in resectable locally advanced disease. Conventional practice is not to place excision lines through areas of peau d'orange for fear of recurrence in such an area. The question can be asked whether this wisdom is still valid in modern practice. No formal cohort studies documenting the histopathology of the skin in areas of peau d'orange have been published, and available descriptions are scanty. To describe the histopathological features of peau d'orange. Consecutive patients undergoing mastectomy for cancer in whom peau d'orange was present were selected over a period of 2 years. Blocks of skin were excised from areas of peau d'orange and examined histologically. The presence, nature and location of malignant cells were recorded and correlated with lymph node pathology. Prior administration of neo-adjuvant chemotherapy was noted. Twenty-six mastectomy specimens were examined. Tumour islands in lymphatics were identified in 10 of the 26 specimens. These tumour groups were found in lymph vessels of both the superficial and deep dermal plexuses. In 1 specimen the presence of malignant cells was equivocal. Metastatic tumour was present in axillary lymph nodes in 19 of 22 specimens. Fourteen patients had been treated with neo-adjuvant chemotherapy, and 5 of their specimens exhibited the presence of tumour cell groups in lymphovascular channels. Tumour cells were present in the lymphatic vessels in areas of peau d'orange in 38% of the specimens studied. It would be expected that placing an excision line in such an area would result in an incomplete cancer operation in a high percentage of, but not all, cases.

Histological differentiation between palmoplantar pustulosis and pompholyx

Palmoplantar pustulosis (PPP) is a chronic and intensely inflammatory skin disease with pustules, erythema and scaling localized to the palms and soles. Pompholyx is characterized by recurrent crops of vesicles on the lateral aspects of the fingers and the palms and soles. Because both PPP and pompholyx share similar clinical and histological features, it is difficult to differentiate between these two diseases even for dermatologists. To compare the histological features of PPP and pompholyx and to analyse their clinical characteristics. The clinical history from 45 patients with PPP and 42 with pompholyx was evaluated. Among these patients, the punch biopsies from acute lesions of 40 PPP patients and 35 pompholyx ones were analysed, blind to the clinical diagnosis. There was no sexual predilection in either group, and 65.5% of PPP patients had smoking history. About half of the patients had concomitant palmoplantar lesions in PPP and pompholyx respectively. In histological evaluation, loss of granular layer, suprapapillary plates thinning, eosinophils in the pustules or vesicles, tortuous capillaries, capillaries touching the undersurface of epidermis and extravasated erythrocytes were statistically significant features of PPP. Confluent parakeratosis, psoriasiform epidermal hyperplasia, clubbing and anastomosing of the rete ridges favoured PPP. Meanwhile, multiple foci of parakeratosis, irregular epidermal hyperplasia and thinning of rete ridges were more often observed in pompholyx. However, dyskeratotic cells, papillary dermal oedema, dilated capillaries and acrosyringium were not significantly different between the two diseases. Several histological features could serve as useful 'clues' to differentiate between PPP and pompholyx.

Sweet-Like Reaction Due to Arthropod Bites

The histopathology of arthropod bite reactions is classically described as "dermal edema" with superficial and middle to deep dermal inflammation in a perivascular and wedge-shaped distribution. The composition of the infiltrate may vary, but a characteristic feature is the presence of prominent eosinophils between collagen bundles. Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is characterized by dermal edema and a dense neutrophilic infiltrate, associated with a constellation of clinical and biological signs. We describe herein 2 cases of arthropod bite reactions with impressive clinical lesions and histopathological findings reminiscent of Sweet syndrome. However, the patients were lacking other criteria for Sweet syndrome and were diagnosed as Sweet-like reaction to arthropod bites. Pathologists should be careful in rendering a diagnosis of neutrophilic dermatosis, which requires clinicopathological correlation, and should consider arthropod bite reactions in the differential diagnosis.

Histologically-validated footpad dermatitis scoring system for use in chicken processing plants

1. Footpad dermatitis (FPD) is a recognised welfare problem in broiler chickens. Broiler feet (n = 54) were examined macroscopically and microscopically to determine a reliable correspondence between macroscopic and histological features, and to devise a scoring system that was relevant to bird welfare and easy to use at processing plants. 2. Three types of footpad lesion were defined based on their severity. Type I were mild lesions, visually characterised by scale enlargement and erythema, and histologically by hyperplasia and hyperkeratosis of the epidermis, superficial dermal congestion and oedema. Type II were moderate, superficial lesions, visually characterised by hypertrophic and hyperkeratotic scales covered with yellowish to brownish exudate, and histologically by a prominent pustular and crust-forming dermatitis. Type III lesions were the most pronounced, visually characterised by a thick dark adherent crust, and histologically by extensive ulceration. 3. On the basis of the severity and extent of these three types of lesions, a 5-point scale was devised, i.e. no or type I lesion (score 1), type II lesion (<50% or >50% of footpad, scores 2 and 3 respectively) and type III lesion (<50% or >50% of footpad, scores 4 and 5 respectively). 4. The scoring system has the advantage of making sense in terms of welfare compared with previous schemes. Furthermore, it is histologically validated and easy to use for the routine assessment of broiler welfare in processing plants.

Clinicopathologic Profile of Hypopigmented Mycosis Fungoides in India

Hypopigmented mycosis fungoides (HMF) is an under recognized disease in India, which is often mistaken for Hansen disease or vitiligo, resulting in delayed diagnosis and treatment. To describe the clinical, histopathologic and immunohistochemical features of HMF in Indian patients. All cases presenting as hypopigmented lesions that were signed out as MF between 2001 and 2009 (15 cases) were included. Clinical data and histopathology slides were reviewed. Immunostains for CD4, CD8, and CD1a were done, where tissue was available. The age ranged from 14 to 38 years with a male preponderance. The commonest presentation was multiple hypopigmented patches on limbs and trunk with the duration of the lesions varying from 4 months to 14 years. All cases showed a psoriasiform/lichenoid epidermal pattern, disproportionate epidermotropism, basilar tagging of lymphocytes, monomorphous lymphocytes, haloed lymphocytes, and wiry dermal collagen. Other important findings were infiltration of hair follicles, larger epidermal lymphocytes, atypia of dermal lymphocytes, and stuffed dermal papillae. Dermal edema was absent in all cases. Immunohistochemistry done on 10 cases showed a CD8 phenotype in 6 cases and CD4 phenotype in the remaining 4 cases. Histopathology supplemented by immunohistochemistry is reliable in making a diagnosis of HMF. It is important to be aware of this uncommon, yet significant disease.

The Clinical and Histological Skin Changes After the Cupping Therapy (Al-Hijamah)

Background: Cupping Therapy (CT) has been reported as treatment for several skin conditions such as acne, post herpetic neuralgia, psoriasis, atopic dermatitis and urticaria. Although it is often considered as part of the Traditional Chinese Medicine (TCM), it has been widely practiced in the Middle East and the rest of the world for centuries. In Basra, a city in the southern part of Iraq, cupping therapy is often used by alternative medicine practitioners for treating skin disorders. However, limited is known about the clinical and histological effects of cupping therapy on the skin. Objectives: To investigate the immediate and delayed effect of CT on the skin, clinically and histologically. Material and Methods: TWe visited alternative and herbal medicine clinics that practice cupping therapy in Basra. Questionnaires were given to the patients and the alternative medicine practitioners to explore their experience with cupping therapy in terms of the presenting complaints and symptoms following therapy. The different types of application techniques and the immediate and delayed clinical changes on the skin following cupping therapy have been recorded. Ten skin biopsies were taken from male participants to investigate the histological changes in the application sites. Results: One hundred and thirty five patients were enrolled in the study. Of them, 102 (75.6%) were males and 33 (24.4 %) were females. The presenting complaints in males were back pain (29.4 %), Sciatica pain (15.7%) then headache (12.7%). In females, the presenting complaints were frozen shoulder (30.3%), back pain (18.2%), joint pain (12.1%) and gynecological causes (9.1%). Skin diseases were the presenting complaints in 4.9% of the males and 3% of the females. They included psoriasis, vitiligo, and eczema. Following cupping therapy, the immediate signs were erythema, swelling, bruising, bleeding, bullae formation and sings of cutting as results of cutting the skin for bloodletting. Patients reported discomfort ranging from slight tingling sensation to severe pain. Delayed clinical effects were scars in 6% of cases and patches of post inflammatory hyper-pigmentation with or without ring of ecchymosis in 4 % of total cases 30 days after cupping therapy. In all other cases complete healing of the skin was within three weeks. No adverse events were noted in our study. Histological changes following cutting and bloodletting were mild oedema, vacuolization and longitudinal fissure as a result of cutting in the epidermis. In the dermis, histological changes were dermal oedema and bleeding in the upper and lower parts of the dermis. No cellular infiltration was noted. Conclusion: Cupping therapy is associated with distinctive early and late clinical changes. However, it is safe procedure and most of these changes are reversible within three weeks. There were no adverse events as a result of the therapy. The efficacy of cupping therapy in treatment is beyond the scope of this study and further studies are needed.

A retrospective analysis of histopathology of 64 cases of lepra reactions

Background:Lepra reactions are not always diagnosable under the microscope. We analyzed skin histopathology in 64 cases of lepra reaction.Aim:To make detailed observations on histopathologic features of type 1 and type 2 lepra reaction (erythema nodosum leprosum, ENL).Materials and Methods:In this retrospective study, we included 64 patients diagnosed during a 3-year period as lepra reaction based on clinico-pathological co-relation.Results:Out of the 64 patients, 22 were of type 1 reaction and 42 of ENL. The most consistent finding in type 1 reaction was papillary dermal edema (86%) followed by pyknosis of lymphocytes (77%) and intercellular edema within granuloma (73%). Surprisingly, folliculotropism of lymphocytes was seen in 55% and subcutaneous infiltration in 36%. In ENL, the most common finding was presence of neutrophils within the granuloma (100%), followed by leukocytoclasia (81%), papillary dermal edema (81%), and neutrophilic panniculitis (69%). Fibrin in the vessel wall or/and granulomas was noted in only 38% while fibrin thrombi in the vessel walls were seen in only 12% of cases.Conclusion:Infiltration of macrophage granulomas by neutrophils is a reliable sign of ENL. Classical signs of vasculitis are not always present in ENL. Folliculotropism and lymphocytic panniculitis were frequent in type 1 reactions while neutrophilic panniculitis was common with ENL.

Clinical and histopathological study of Simulium (blackfly) dermatitis from North‐Eastern India – a report

Simulium dermatitis is a common problem in humans and animals in areas where Simulium species occur. It is characterized by chronic eruptions of pruritic papules, vesicles, and erythematous wheals resulting from a hypersensitivity reaction to biting of simuliids or blackflies. It can result in severe skin complications where the man-biting species of Simulium are available. We report two clinical cases of Simulium dermatitis from the North-Eastern region of India. Histopathological study was carried out in one of the cases and the other one was successfully treated with medication. Clinical features like intense itching, which accompanies the eruption, resulting in excoriations, scarring, and permanent hyperpigmentation were reported. Histopathological study revealed the characteristic features of Simulium bite reaction, such as vesicles filled with serous fluid, dermal edema, and perivascular infiltrates rich in eosinophils and lymphocytes. The clinical manifestations and severity of Simulium dermatitis are serious matters of concern in hypersensitive persons.

Histiocytoid Sweet syndrome: Report of two cases and review of the literature

Histiocytoid Sweet syndrome (SS) is a rare inflammatory disease that has recently been described as a variant of classic SS. Histopathologically, histiocytoid SS is characterized by papillary dermal edema with infiltration of histiocyte-like cells into the upper dermis. These microscopic features may be similar to those of leukemia cutis, which involves infiltration of malignant blasts into the dermis. However, the treatment and clinical prognosis of these two conditions are quite different. Here, we report the case of two Taiwanese patients with histiocytoid SS. Interestingly, one of the patients had a history of myelodysplastic syndrome and was initially considered to have ongoing leukemic transformation with concomitant leukemia cutis. Finally, the patient was diagnosed with histiocytoid SS based on histological findings, and both patients were successfully treated with low-dose oral corticosteroids.

Intradermal injections of equine allogeneic umbilical cord-derived mesenchymal stem cells are well tolerated and do not elicit immediate or delayed hypersensitivity reactions

BACKGROUND AIMS. The use of allogeneic mesenchymal stem cells (MSC) to treat acute equine lesions would greatly expand equine cellular therapy options; however, the safety and antigenicity of these cells have not been well-studied. We hypothesized that equine allogeneic umbilical cord tissue (UCT)-derived MSC would not elicit acute graft rejection or a delayed-type hypersensitivity response when injected intradermally. METHODS. Six Quarterhorse yearlings received 12 intradermal injections (autologous MSC, allogeneic MSC, positive control and negative control, in triplicate) followed by the same series of 12 injections, 3-4 weeks later, at another site. Wheals were measured and palpated at 0.25, 4, 24, 48, 72 h and 7 days post-injection. Biopsies were obtained at 48 and 72 h and 7 days post-injection. Mixed leukocyte reactions were performed 1 week prior to the first injections and 3 weeks after the second injections. RESULTS. There were no adverse local or systemic responses to two intradermal injections of allogeneic MSC. MSC injection resulted in minor wheal formation, characterized by mild dermatitis, dermal edema and endothelial hyperplasia, that fully resolved by 48-72 h. No differences were noted between allogeneic and autologous MSC. The second injection of MSC did not elicit more significant physical or histomorphologic alterations compared with the first MSC injection. Neither allogeneic nor autologous UCT-derived MSC stimulated or suppressed baseline T-cell proliferation in vitro prior to or after two MSC administrations. CONCLUSIONS. Equine allogeneic UCT MSC may be safely administered intradermally on multiple occasions without eliciting a measurable cellular immune response.

Case of insulin edema occurring during intensive insulin therapy after bone marrow transplantation

A 50-year-old female patient, who had had a long-term history of myelodysplastic syndrome and type II diabetes mellitus, had developed acute myelogenous leukemia and received allogeneic bone marrow transplantation (BMT). She was being treated with tacrolimus, methotrexate and prednisolone for prophylaxis and treatment of graft-versus-host disease, and with intensive insulin therapy for better glycemic control. The patient suddenly developed marked leg edema at 27 days after starting intensive insulin therapy (on day 40 after BMT) without coexistence or exacerbation of apparent causes such as renal failure, cardiac dysfunction or leg thrombosis around the onset of leg edema. Interestingly, the leg edema regressed soon after daytime hyperglycemia and intensive insulin therapy were performed. Histopathological examination revealed slight dermal edema and small bullae with little inflammatory infiltration but no signs of autoimmune blistering diseases or vasculitis. These findings indicate that the present case may be considered a form of so-called insulin edema occurring during intensive insulin therapy after BMT.

Recurrent Gianotti-Crosti syndrome

To the Editor: Gianotti-Crosti syndrome (GCS) classically presents in children as a self-limited, symmetric erythematous papular eruption affecting the cheeks, extremities, and buttocks. While initial reports implicated hepatitis B virus as the etiologic agent, many other bacterial, viral, and vaccine triggers have since been described. A previously healthy 2-year-old boy presented with a 3-week history of a cutaneous eruption that initially appeared on his legs and subsequently progressed to affect his arms and face. Two weeks after onset of the eruption, he was immunized with intramuscular Vaxigrip influenza vaccination (Sanofi Pasteur), and new lesions appeared at the immunization site on his right upper arm. Physical examination demonstrated an afebrile child with erythematous papules on the cheeks, arms, and legs (Fig 1). He had a localized papular eruption on his right upper arm (Fig 2). There was no lymphadenopathy or hepatosplenomegaly. Laboratory investigations revealed leukocytosis (white cell count, 14,600/mm) with a normal differential, reactive thrombocytosis ( platelet count, 1,032,000/mm), a positive urine culture for cytomegalovirus, and positive IgM serology for Epstein-Barr virus (EBV). Histopathologic examination of a skin biopsy specimen from the right buttock revealed a perivascular and somewhat interstitial lymphocytic infiltrate in the superficial and mid-dermis with intraepidermal exocytosis of lymphocytes, mild spongiosis and papillary dermal edema. He was treated with 2.5% hydrocortisone cream, and the eruption resolved. Twelve months later, he presented with a similar papular eruption localized to the left upper arm at the site of a recent intramuscular influenza vaccination (Vaxigrip). Although an infection represents the most important etiologic agent, a second event involving immunomodulation might lead to further disease accentuation, thus explaining the association of GCS with vaccinations. In our case, there was evidence of both cytomegalovirus (CMV) and EBV infection as well as a recent history of immunization. Localized accentuation of papules at the immunization site was unusual, as previous cases of GCS following immunizations have had a widespread and typically symmetric eruption. It is possible that trauma from the injection or a component of the vaccine elicited a Koebner response, causing local accentuation. There are no previous reports of recurrence of vaccine-associated GCS. One report documented recurrence with two different infectious triggers. As GCS is a mild and selflimiting disease, further vaccinations are not contraindicated. Andrei I. Metelitsa, MD, FRCPC, and Loretta Fiorillo, MD, FRCPC