Implementation of a Teledermatology Electronic Consultation Program to Improve the Care of Patients with Inflammatory Bowel Disease.

Introduction: Skin lesions are a common extraintestinal manifestation associated with inflammatory bowel disease (IBD), although they may also appear as a complication of IBD treatment. Prompt referral to the dermatologist can be very helpful in practice. Teledermatology complements the traditional in-person health care modality, improving access to dermatological care. Objective: To evaluate the impact of a store-and-forward teledermatology electronic consultation (e-consult) program on the care of IBD patients. Methods: A retrospective study assessing the outcomes of our teledermatology program over its first 2 years of implementation. Results: A total of 39 consultations involving 33 patients (69.2% women, mean age 39.6 years [12-63]) were conducted. The mean number of teleconsultations was 2.8 per month in the initial implementation stage: 33 consultations were carried out in patients with Crohn's disease and 6 in ulcerative colitis. Only 18% of the patients had an active flare-up. The most frequent reason for the e-consult was paradoxical psoriasiform lesions (n = 13, 33.3%), commonly related with anti-tumor necrosis factor agents (70% of the patients) and hidradenitis suppurativa (n = 4, 10.3%). Resolution was achieved in 87% of patients, with a mean waiting time of 4.7 days (0-14). Almost all patients (97%) were satisfied with our program, and considered the referral through the program to be appropriate (92%). Best valued features were the reduced waiting time and the coordinated approach between the two departments involved. Conclusions: Dermatology e-consult is an efficient and useful means of optimizing IBD patient care.

Variation in Pleiotropic Hub Gene Expression Is Associated with Interspecific Differences in Head Shape and Eye Size in Drosophila.

Revealing the mechanisms underlying the breathtaking morphological diversity observed in nature is a major challenge in Biology. It has been established that recurrent mutations in hotspot genes cause the repeated evolution of morphological traits, such as body pigmentation or the gain and loss of structures. To date, however, it remains elusive whether hotspot genes contribute to natural variation in the size and shape of organs. As natural variation in head morphology is pervasive in Drosophila, we studied the molecular and developmental basis of differences in compound eye size and head shape in two closely related Drosophila species. We show differences in the progression of retinal differentiation between species and we applied comparative transcriptomics and chromatin accessibility data to identify the GATA transcription factor Pannier (Pnr) as central factor associated with these differences. Although the genetic manipulation of Pnr affected multiple aspects of dorsal head development, the effect of natural variation is restricted to a subset of the phenotypic space. We present data suggesting that this developmental constraint is caused by the coevolution of expression of pnr and its cofactor u-shaped (ush). We propose that natural variation in expression or function of highly connected developmental regulators with pleiotropic functions is a major driver for morphological evolution and we discuss implications on gene regulatory network evolution. In comparison to previous findings, our data strongly suggest that evolutionary hotspots are not the only contributors to the repeated evolution of eye size and head shape in Drosophila.

Ex Vivo High-Frequency Ultrasound for Assessment of Basal Cell Carcinoma.

The use of Mohs micrographic surgery for poorly defined cutaneous tumors is present in a few departments in Spain. Reintervention is occasionally necessary when the margins of the surgical specimen are invaded by the tumor. We propose the use of ultrasound to assess these margins by imaging the surgical specimen once excised.

Hardness and Painful Lesion of the Breast.

Dear Editor, Lupus panniculitis or lupus profundus is a rare inflammatory complication found in patients with systemic lupus erythematosus (SLE), or discoid lupus erythematosus (DLE) (1). When the breast is involved, the term lupus mastitis (LM) is used. This disease involving the breast is rare, and the lesions may precede, coincide with, or occur later than the onset of other lupus lesions. Tissue biopsy is required to confirm the suspected diagnoses of LM. We report a case of a patient with lupus mastitis due to the important differential diagnosis. A 60-year-old woman presented with a painful nodular lesion in her left breast that had appeared 15 days ago (Figure 1, a). She had been previously diagnosed with discoid lupus erythematosus 3 years ago. Physical examination revealed a deep and firm erythematous subcutaneous nodule without overlying skin involvement in the lower-central portion of the left breast. Laboratory findings were positive for antinuclear antibodies (1:80) and double-stranded deoxynucleic acid antibodies (1:10). Mammography and ultrasounds showed an area of increased density and irregular breast tissue along with an important thickening of the overlying skin (Figure 1, b). On suspicion of malignancy, a needle biopsy of the breast lesion was performed and showed vacuolar alteration and lymphocytic infiltrate in the basal layer. Subcutaneous fat showed a lobular panniculitis with a prominent lymphocytic infiltrate and hyalinization of the fat lobules (hyaline fat necrosis). Direct immunofluorescence of the face biopsy revealed IgA, IgG, IgM, and C3 granular deposition. Based on these results, a diagnosis of lupus mastitis associated with DLE was established. Antimalarial therapy resulted in complete resolution of the clinical features. Three years later, the patient presented with a disfiguring atrophy with retraction in the damaged areas of the breast (Figure 2). Lupus mastitis is a very unusual disease that most commonly affects middle-aged women. The first case of LM was described by Tuffanelli in 1971. The lesions usually present following the diagnosis of SLE/DLE; however, on rare occasions they may be observed earlier (2). The histophysiology of this disease remains unclear, but the predominant theory suggests an autoimmune-related etiology. Corroborating evidence for this theory includes the finding of immune complexes, both at the basement membrane of the dermal-epidermal junction and in the blood vessels in the areas of panniculitis (3). Lupus mastitis may be present in the breast as single or multiple subcutaneous nodules that may be tender or painful and can progress to chronic ulcers over time or resolve, leaving atrophic scars. The overlying skin can be normal, erythematous, poikilodermic or ulcerated. When skin changes are prominent, the lesion may clinically and radiologically mimic inflammatory breast carcinoma. Mammographic and ultrasounds findings include an ill-defined breast density with or without associated microcalcifications (4). Histologically, this disease is characterized by lobular lymphocytic panniculitis and predominantly involves the fat lobule and the presence of anucleated adipocytes in a background of a glassy-appearing collagenous stroma (hyaline fat necrosis). Fibrinoid necrosis of the vessel wall has also been reported, but is usually absent (5). Differential diagnosis of lupus mastitis includes inflammatory breast carcinoma, primary medullary carcinoma, and other immune-mediated inflammatory conditions such as diabetic mastopathy. The first line of treatment the use of antimalarial drugs such as hydroxychloroquine. Systemic steroids and cyclophosphamide have also been used. Surgical treatment should be considered only in patients who do not respond to management with medications. In summary, we reported a case of lupus mastitis in a patient with discoid lupus erythematosus. This dermatosis should be considered in the differential diagnosis of breast lesions in lupus patients, and a biopsy of the breast lesion is essential to reject suspected malignancy. If the disease is left untreated, unsightly atrophy will appear; it is thus important to diagnose early on. The course of the disease tends to be chronic with remission and flares, so patients should be followed-up regularly due to the risk of recurrences in the same area or in a different location.

Removal of Anisakis simplex allergens from infected fish during the washing step of surimi production.

BACKGOUND: The washing operation of fish muscle is one of the key steps in the production of surimi. The aim of this study was to assess in parasitised minced fish the effect of the washing steps on the allergen removal of Anisakis simplex and on protein yield during surimi processing. Experimentally infected hake (Merluccius merluccius) (50 Anisakis simplex s.s L3 larvae per 100 g of muscle) underwent three successive washing steps with water, phosphate buffer (20 mmol L(-1) ), sodium bicarbonate (60 mmol L(-1) ), or sodium hypochlorite (0.27 mmol L(-1) ) in the surimi processing (4 kg muscle, 1:4 w/v for each solution). Total protein concentration and A. simplex antigens and allergens were evaluated in each waste fraction. RESULTS: The highest removal of Ani s 4 and A. simplex antigens was achieved by using phosphate buffer, together with a good protein yield in the raw surimi. Decrease of the concentration of allergens and antigens as a function of the washing steps rendered a linear trend (R(2) = 0.95 and 0.98 for Ani s 4 and A. simplex antigens, respectively). CONCLUSION: The conditions for an optimal removal of Anisakis allergens can be established and calculated as a function of the washing steps. This approach opens a line to utilise parasitised fish in a safer way. © 2014 Society of Chemical Industry.

Antigenicity of Anisakis simplex s.s. L3 in parasitized fish after heating conditions used in the canning processing.

BACKGROUND: Some technological and food processing treatments applied to parasitized fish kill the Anisakis larvae and prevent infection and sensitization of consumers. However, residual allergenic activity of parasite allergens has been shown. The aim here was to study the effect of different heat treatments used in the fish canning processing industry on the antigen recognition of Anisakis L3. Bigeye tuna (Thunnus obesus) and yellowfin tuna (Thunnus albacares) were experimentally infected with live L3 Anisakis. After 48 h at 5 ± 1 °C, brine was added to the muscle, which was then canned raw (live larvae) or heated (90 °C, 30 min) (dead larvae) and treated at 113 °C for 60 min or at 115 °C for 90 min. Anisakis antigens and Ani s 4 were detected with anti-crude extract and anti-Ani s 4 antisera respectively. RESULTS: Ani s 4 decreased in all lots, but the muscle retained part of the allergenicity irrespective of the canning method, as observed by immunohistochemistry. Dot blot analysis showed a high loss of Ani s 4 recognition after canning, but residual antigenicity was present. CONCLUSION: The results indicate that heat treatment for sterilization under the conditions studied produces a decrease in Ani s 4 and suggest a potential exposure risk for Anisakis-sensitized patients.

[Superimposed lichen planus pigmentosus]. / Liquen plano pigmentoso sobreimpuesto.

Lichen planus pigmentosus is an uncommon variant of lichen planus that is characterized by the insidious onset of dark brown macules in sun-exposed areas and flexural folds. Superimposed linear lichen planus is an exceedingly rare disorder, but it has been found in both lichen planopilaris and lichen planus types. A 39-year-old woman is presented showing a segmental and linear lichen planus associated with non-segmental lesions meeting all criteria for the diagnosis of superimposed linear planus pigmentosus. The segmental lesions were always more pronounced.

Viability and antigenicity of anisakis simplex after conventional and microwave heating at fixed temperatures.

Inactivation of parasites in food by microwave treatment may vary due to differences in the characteristics of microwave ovens and food properties. Microwave treatment in standard domestic ovens results in hot and cold spots, and the microwaves do not penetrate all areas of the samples depending on the thickness, which makes it difficult to compare microwave with conventional heat treatments. The viability of Anisakis simplex (isolated larvae and infected fish muscle) heated in a microwave oven with precise temperature control was compared with that of larvae heated in a water bath to investigate any additional effect of the microwaves. At a given temperature, less time was required to kill the larvae by microwaves than by heated water. Microwave treatment killed A. simplex larvae faster than did conventional cooking when the microwaves fully penetrated the samples and resulted in fewer changes in the fish muscle. However, the heat-stable allergen Ani s 4 was detected by immunohistochemistry in the fish muscle after both heat treatments, even at 70°C, suggesting that Ani s 4 allergens were released from the larvae into the surrounding tissue and that the tissues retained their allergenicity even after the larvae were killed by both heat treatments. Thus, microwave cooking will not render fish safe for individuals already sensitized to A. simplex heat-resistant allergens.

A novel heterozygous point mutation in the p63 gene in a patient with ectodermal dysplasia associated with B-cell leukemia.

We report a 7-year-old boy with a past medical history of B-cell leukemia with dysmorphic features, including cleft palate, hypotrichosis with trichorrhexis nodosa, hypohidrosis, oligodontia, and ridging of nails. A heterozygous germline mutation, Ala111Thr, in the p63 gene was detected in the boy and in his mother, who had no clinical expression. This case emphasizes the spectrum of different phenotypical manifestations of mutations in the p63 gene and underlines the possible role of this gene as a tumor suppressor.

Genetic variability of Anisakis simplex s.s. parasitizing European hake (Merluccius merluccius) in the Little Sole Bank area in the Northeast Atlantic.

In this study, we researched the presence of anisakids in specimens of Merluccius merluccius caught in the area of Little Sole Bank, in the Northeast Atlantic, and found that 100% of the European hake examined were infected and showed high average values of abundance (976.88) and intensity (976.88). The larvae were identified in morphological terms as morphotype type I and in molecular terms as Anisakis simplex s.s via polymerase chain reaction (PCR) restriction fragment length polymorphism of the rDNA. The genetic variability of the A. simplex s.s population in the North Atlantic is notable, with at least two ribosomal and three mitochondrial haplotypes which are different from the specimen used as control, reflecting the diversity of this species, an aspect which has scarcely been studied to date. The cox-2 gene appears to be an interesting candidate for generating new genetic markers which can be applied to differentiate between A. simplex s.s and Anisakis pegreffii. We detected 11 fixed differences in this gene, and it also offers the advantage of being easily amplified by PCR. The high prevalence of infection by A. simplex s.s and the extremely high average intensity and abundance values can have significant repercussions on public health, especially among populations which regularly eat insufficiently cooked or raw fish and have a certain genetic predisposition; the genetic variability of the parasite could be another factor to take into account.

Quantification of Anisakis simplex allergens in fresh, long-term frozen, and cooked fish muscle.

Fish-borne parasitic zoonoses such as Anisakiasis were once limited to people living in countries where raw or undercooked fish is traditionally consumed. Nowadays, several factors, such as the growing international markets, the improved transportation systems, the population movements, and the expansion of ethnic ways of cooking in developed countries, have increased the population exposed to these parasites. Improved diagnosis technology and a better knowledge of the symptoms by clinicians have increased the Anisakiasis cases worldwide. Dietary recommendations to Anisakis-sensitized patients include the consumption of frozen or well-cooked fish, but these probably do not defend sensitized patients from allergen exposure. The aim of our work was to develop a sensitive and specific method to detect and quantify Anisakis simplex allergens in fish muscle and its derivatives. Protein extraction was made in saline buffer followed by preparation under acid conditions. A. simplex antigens were detected by IgG immunoblot and quantified by dot blot. The allergenic properties of the extracts were assessed by IgE immunoblotting and basophil activation test. We were able to detect less than 1 ppm of A. simplex antigens, among them the allergen Ani s 4, in fish muscle with no cross-reactions and with a recovery rate of 82.5%. A. simplex antigens were detected in hakes and anchovies but not in sardines, red mullets, or shellfish. We detected A. simplex allergens in cooked hakes and also in hake stock. We proved that A. simplex allergens are preserved in long-term frozen storage (-20 degrees C +/- 2 degrees C for 11 months) of parasitized hakes. Basophil activation tests have proven the capability of the A. simplex-positive fish extracts to induce allergic symptoms.

Antigenicity and viability of Anisakis larvae infesting hake heated at different time-temperature conditions.

Heat treatments (40 to 94 degrees Celsius, 30 s to 60 min) were applied to different batches of Anisakis simplex L3 larvae isolated from hake ovaries and viscera to study the effect of heat on the viability of the larvae measured as mobility, emission of fluorescence under UV light, and changes in color after staining with specific dyes, and on A. simplex antigenic proteins. The aim was to determine the lowest time-temperature conditions needed to kill the larvae to avoid anisakiasis in consumers, and to evaluate whether high temperature modifies the antigenicity of A. simplex extracts. Heating at 60 degrees Celsius for 10 min (recommended by some authors) was considered unsafe, as differences in viability between batches were found, with some larvae presenting spontaneous movements in one batch. At higher temperatures (> or = 70 degrees Celsius for > or = 1 min), no movement of the larvae was observed. Antigenic protein Ani s 4 and A. simplex crude antigens were detected in the larvae heated at 94 + or - 1 degrees Celsius for 3 min. This indicates that allergic symptoms could be provoked in previously sensitized consumers, even if the larvae were killed by heat treatment.

[Down syndrome: another cause of immunosuppression associated with multiple eruptive dermatofibromas?]. / Síndrome de Down: ¿otra causa de inmunosupresión asociada con dermatofibromas eruptivos múltiples?

The term "multiple eruptive dermatofibromas" usually refers to a clinical situation characterized by the development of between five and eight dermatofibromas during a period of up to four months. It is usually linked to immunodeficiency associated conditions as autoimmune disorders, hematologic malignancies, HIV infection, and transplants. We report three patients with Down syndrome. One patient had psoriatic arthritis under treatment with methotrexate, one had Graves-Basedow disease, and one had hypercholesterolemia. All three patients developed multiple eruptive dermatofibromas. We suggest that the immunologic disturbances associated with Down syndrome, together with other underlying conditions present in these patients, could trigger the development of cutaneous lesions.

Anisakis antigens detected in fish muscle infested with Anisakis simplex L3.

Anisakis simplex is a fish parasite that is a public health risk to those consuming raw or poorly cooked marine fish and cephalopods because of the possibility of becoming infested with live larvae. In humans, penetration of the larvae into the gastrointestinal track can cause acute and chronic symptoms and allergic anisakiasis. Excretion and secretion products released by the larvae are thought to play a role in migration through the tissues and induce an immunoglobulin E-mediated immune response. The aim of this preliminary study was to detect parasite antigens and allergens in fish tissues surrounding the migrating larvae. Hake and anchovy fillets were artificially parasitized with Anisakis larvae and stored in chilled conditions for 5 days. Larvae were evaluated for fluorescence, fish muscle tissue was examined with transmission electron microscopy, and immunohistochemical reactions of two rabbit polyclonal antisera against a parasite crude extract and the allergen Ani s 4 were recorded. Larvae immediately migrated into the fish muscle, and no emission of bluish fluorescence was observed. Fish muscle areas in contact with the parasite showed disruptions in the structure and inclusion of granules within sarcomeres. Both parasite antigens and the Ani s 4 allergen were located in areas close to the larvae and where sarcomere structure was preserved. These findings indicate that parasite antigens and allergens are dispersed into the muscle and might cause allergic symptoms such as dyspnea, vomiting, diarrhea, urticaria, angioedema, or anaphylaxis in some individuals sensitive to A. simplex.

Allergenic properties and cuticle microstructure of Anisakis simplex L3 after freezing and pepsin digestion.

This article examines the viability of and the alterations to the larval cuticle and the pattern of the antigens released when live or frozen Anisakis simplex larvae were treated with acid and pepsin. The results showed that freezing did not greatly alter the larva body. If ruptures were observed, the antigen release to the incubation media was not enhanced, and most of the antigenic content was retained inside the bodies of the larvae. The immunoblotting assay demonstrated that most of the antigens released, including the allergen Ani s 4, were resistant to pepsin. Freezing killed the larvae, but their survival was not compromised by acid treatment or pepsin digestion when kept chilled. All these findings support recommendations about freezing fish for consumption raw or undercooked to prevent human infection by A. simplex larvae. However, our data show that the antigenicity of the larvae is preserved after freezing and may explain why some sensitized patients develop symptoms after ingestion of infested frozen fish.