Spanish Guidelines for Diagnosis, Management, Treatment, and Prevention of DRESS Syndrome.

BACKGROUND AND OBJECTIVE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a complex multisystemic severe drug hypersensitivity reaction whose diagnosis and management are troublesome. DRESS syndrome requires management by various specialists. The correct identification of the culprit drug is essential to ensure safe future therapeutic options for the patient. There are no previous Spanish guidelines or consensus statements on DRESS syndrome. Objective: To draft a review and guidelines on the clinical diagnosis, allergy work-up, management, treatment, and prevention of DRESS syndrome in light of currently available scientific evidence and the experience of experts from multiple disciplines. METHODS: These guidelines were drafted by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC), together with other medical specialists involved in the management of DRESS syndrome and researchers from the PIELenRed consortium. A review was conducted of scientific papers on DRESS syndrome, and the expert panel evaluated the quality of the evidence of the literature and provided grades of recommendation. Whenever evidence was lacking, a consensus was reached among the experts. RESULTS: The first Spanish guidelines on DRESS syndrome are now being published. Important aspects have been addressed, including practical recommendations about clinical diagnosis, identification of the culprit drug through the Spanish pharmacovigilance system algorithm, and the allergy work-up. Recommendations are provided on management, treatment, and prevention. Algorithms for the management of DRESS in the acute and recovery phases have been drawn up. Expert consensus-based stepwise guidelines for the management and treatment of DRESS syndrome are provided.

Clinical epidemiology of childhood cancer in Central America and Caribbean countries.

BACKGROUND: Countries with scarce resources have the right to appropriate essential health care but very few reports discuss how this can be achieved. We assessed the survival of a large cohort of pediatric oncological patients to provide hard data on which to base realistic evaluation and planning schemes. PATIENTS AND METHODS: This multicenter retrospective survey covered consecutively diagnosed and treated patients admitted to eight national level hospitals in seven countries in Central America and the Caribbean. The research protocol was discussed extensively, so the data to be collected and the criteria for their evaluation were clearly pre-defined. We analysed 2214 patients diagnosed between 1996 and 1999 with various cancers, classified as hemato-oncological disorders (70%) and solid tumors (30%). RESULTS: Three-year overall survival was 48.4% [standard error (SE) 1.3]. Detailed analysis of acute lymphoblastic leukemia highlighted the wide intercountry variability: 3-year survival was 62.2% (SE 5.3) in Cuba, 74.2% (SE 3.3) in Costa Rica, 61.7% (SE 4.9) in Nicaragua, and lower in the other four countries. CONCLUSIONS: The yield of diagnostic-therapeutic protocols depends largely on the context of care in which they are applied. This paper documents the importance of including epidemiological research in interventions for cooperation in complex health areas such as pediatric oncology.

The concept of the sentinel lymph node.

Lymphangiograms performed via direct cannulation of lymphatic ducts demonstrate drainage of the lymph into a specific lymph node center, the so-called SLN. Contrast materials such as lipiodol, injected directly into the tissue (e.g., tongue) can demonstrate the SLN. As the neoplastic cells can be carried through the lymphatic ducts, the SLN is the first filter in the lymphatic pathway, and the SLN is indeed the most likely regional node to harbor metastatic carcinoma. The results of these efforts challenged the surgical community worldwide to recognize the importance of the concept of SLN. This concept needs to be inexpensive and easily applied in daily practice. Recently, brilliant investigators have found that using "blue dye" and or radioactive tracers are a resourceful way in identifying SLN and have applied the benefits in their daily practice. Morton [15] using the "blue dye" and Krag [1] using radioactive tracers are pioneers in the application of these concepts in other malignant diseases. The SLN concept today is feasible to apply in the investigation, diagnosis, staging and treatment of almost all solid tumors in human pathology. Numerous elegant reports have proved the validation of the concept [2, 7-9, 11, 12, 16, 17, 20, 21, 26-28].

Application of the sentinel node concept in urogenital cancer.

Pre and intra-operative lymphatic mapping and SLN biopsy is readily available in the armamentarium of Urologic Surgical Oncology. The concept of the SLN should be considered for diagnosis and therapy. Ongoing studies are investigating the impact of SLN biopsy on survival as well as the prognostic significance of micro-metastasis founded by histopathology and immunohistological techniques. The concept is simple, the operatory technique is easy, and the blue dye and radioactive agents are available anywhere. The validation in penile carcinoma has demonstrated, based on experience, that metastasis does not occur in other lymph nodes if the SLN is free of metastasis. Its applicability in other areas of urology is still awaiting the enthusiasm of investigators.

Gastroallergic anisakiasis: borderline between food allergy and parasitic disease-clinical and allergologic evaluation of 20 patients with confirmed acute parasitism by Anisakis simplex.

BACKGROUND: Human subjects can be parasitized by Anisakis simplex by eating raw or undercooked fish. Gastric anisakiasis is probably the most frequent clinical entity presenting with severe epigastric pain, vomiting, and diarrhea. In gastroallergic anisakiasis hypersensitivity symptoms predominate. OBJECTIVE: We sought to describe clinical features, laboratory data, and gastroscopic findings in gastroallergic anisakiasis. METHODS: We selected 40 patients presenting to the emergency department with an acute allergic reaction, and if we suspected acute parasitism by A simplex, a fiberoptic gastroscopy was performed. In 20 patients we could detect one or more nematodes; these patients are referred to as group A. Those in whom no worm could be found are referred to as group B (n = 20). A detailed history, clinical features, gastroscopic findings, laboratory data, and skin prick test responses were compared. RESULTS: Long-time intervals of up to 26 hours between fish intake and onset of hypersensitivity symptoms were found (group A, 5.4 +/- 6.3 hours; group B, 5.3 +/- 2.6 hours). Patients in groups A and B did not differ with respect to allergic symptoms (urticaria, angioedema, erythema, bronchospasm, and anaphylaxis) or the mainly light abdominal symptoms (upper abdominal pain, nausea, vomiting, and diarrhea). No significant differences were found with respect to age, time interval between fish intake and onset of symptoms, white cell and eosinophil counts, specific IgE levels against A simplex, or total IgE levels. CONCLUSIONS: The peculiar sometimes long-time interval between fish intake and onset of allergic symptoms render the diagnosis difficult. An early gastroscopy can confirm the diagnosis and prevent complications. We suggest that gastroallergic anisakiasis be considered a distinct clinical entity in which the predominant symptoms are hypersensitivity symptoms and in which the correct diagnosis is not only important in the management of the acute reaction but also in the prevention of further allergic episodes.

Molecular analysis of resistance to interferon in patients with laryngeal papillomatosis.

Although interferon (IFN)-alpha has been used successfully as an adjuvant therapy in laryngeal papillomatosis, some patients are resistant to this treatment. In order to know which patients will benefit from the therapy, we have tried to find a relationship between the IFN response and the viral and host parameters in the lesion. Detection of viral type and copy numbers by polymerase chain reaction (PCR) showed that all patients infected with human papillomavirus (HPV)-11 were sensitive to the treatment, in contrast to those infected with HPV-6. These differences could be explained in part by the inability of HPV-11 E7 to inhibit the induction of an IFN-responsive element, whereas HPV-6 E7 almost completely inhibited the activity of this promoter in transient transfection experiments. Local immune status in the lesion showed that all HPV-11-infected patients had detectable levels of interleukin (IL)-15 and IFN-gamma mRNA, in contrast to HPV-6-infected patients, in whom mRNA for these cytokines was almost absent. Viral copy numbers and levels of IL-4 mRNA could not be correlated with IFN response. Only one patient resistant to recombinant IFN-alpha2b and negative for HPV DNA presented high titers of neutralizing anti-IFN-alpha2b antibodies. This patient became sensitive when natural IFN-alpha was administered. These results suggest that response to IFN may be a complex phenomenon resulting from the interaction between viral and host elements.

Delayed hypersensitivity to enoxaparin.

A 65-year-old woman experienced immediate itchy erythematous patches at the subcutaneous injection sites of sodium enoxaparin. An erythematous and infiltrated 40 x 20 mm lesion on the abdominal wall could be observed at the site of enoxaparin injection when she was referred to our clinic 48 h after injection. Lesions subsided spontaneously within 1 week. She had been on this treatment 1 and 3 years before without any adverse reaction. To clarify the nature of the reaction, epicutaneous tests with sodium enoxaparin, calcium nadroparin and calcium heparin were performed, all with negative results. Skin prick test with sodium enoxaparin was also negative. Biopsy of the cutaneous lesion showed spongiotic dermatitis, strongly suggesting a delayed hypersensitivity mechanism. We report here on a new case of delayed hypersensitivity to enoxaparin. Being female, overweight and having prolonged application of the drug were suggested risk factors present in our patient. Biopsy was essential for diagnosis. Although type IV hypersensitivity reactions to enoxaparin are rare, we should start to suspect this condition in order not to underdiagnose it.

Thirteen cystic fibrosis patients, 12 compound heterozygous and one homozygous for the missense mutation G85E: a pancreatic sufficiency/insufficiency mutation with variable clinical presentation.

To study the severity of mutation G85E, located in the first membrane spanning domain of the CFTR gene, we studied the clinical features of 13 Spanish patients with cystic fibrosis (CF) carrying this mutation. G85E accounts for about 1% of Spanish CF alleles. One patient was homozygous G85E/G85E and the rest were compound heterozygotes for G85E and other mutations (delta F508 nine patients, delta I507 two patients, and 712-1G > T one patient). The characteristics of the pooled G85E/any mutation group were compared with those of 30 delta F508 homozygotes. Mean age at diagnosis and percentage of ideal height for age were higher in the G85E/any mutation group (4.2 (SD 4.7) v 2.4 (SD 2.3), p < 0.05, and 102.8 (SD 4.7) v 97.8 (SD 4.1), p < 0.01), both probably related to the greater prevalence of pancreatic sufficiency (70% v 0%, p < 0.01). The G85E homozygote was pancreatic sufficient. Sweat sodium levels were slightly higher, and salt loss related problems more frequent, in the G85E/any group. Two of the G85E patients died of respiratory failure aged 6 and 14 years. Striking discordance in the phenotype was observed in two pairs of sibs, one of them dizygotic twins, suggesting that factors, genetic and environmental, other than CFTR genotype are important in determining CF phenotype.

Anatomy and biopsy of sentinel lymph nodes.

Lymphangiograms performed via the dorsal lymphatics of the penis demonstrate drainage into a specific lymph node center, the so-called sentinel lymph node, which is located close to the superficial epigastric vein between the latter and the superficial external pudendal vein. Anatomically, clinically, and pathologically, the sentinel lymph node is the first site of metastasis and often is the only lymph node involved. We recommend preliminary bilateral sentinel lymph node biopsy, with inguinofemoral dissection being performed only when this node is involved. If the biopsies are negative for metastases, no further surgical therapy is immediately indicated, and the patient needs to be observed closely with monthly examination for 1 year and examination every 2 months for 3 years. The clinical staging of cancer of the penis needs a new review for further evaluation of different modalities of treatment. Sentinel lymph node biopsy must not be used to determine whether node dissection is needed in patients with evident clinically positive nodes. Also, the concept of sentinel lymph node should not be applied in the management of patients who will not be available for frequent follow-up. If during physical examination, suspect lymph nodes are found other than the classic sentinel node, these lymph nodes must be removed for staging and subsequent treatment planned according to the histologic report.

Synovial chondrometaplasia of the temporomandibular joint: report of case.

A case of synovial chondrometaplasia of the temporomandibular joint is presented with a discussion of the pathologic findings, diagnosis, and treatment. This is a highly uncommon, benign lesion of this joint that affects women more often than men. Since the histologic appearance of some of the tissue cells may resemble malignant changes, care should be taken not to confuse this condition with chondrosarcoma.

An approach for the treatment of penile carcinoma.

One hundred cases were studied in detail using lymphangiograms (LAG), anatomic dissections, and/or microscopic evaluation. LAG performed via the dorsal lymphatics of the penis demonstrate the existence of specific lymph node center, the so-called sentinel lymph node (SLN). This appears to be the primary site of metastases from penile carcinoma. The SLN is visualized radiographically, on the antero-posterior view, at the junction of the femoral head and the ascending ramus of the pubis. Anatomically, the SLN is part of the lymphatic system around the superficial epigastric vein. Forty-six SLN biopsies were performed with 15 positive for metastatic disease. In these 15 patients, an inguinofemoroiliac dissection was performed; in 12 cases there was no involvement of other lymph nodes. Lymphatic channels draining into the iliac lymph nodes without first draining into the sentinel lymph node were never demonstrated, nor were the inguinal-femoral lymph nodes involved in the absence of SLN involvement. On this bases, we recommend preliminary bilateral SLN biopsy to be followed by inguinofemoroiliac dissection when biopsy of the SLN biopsy to be followed by inguinofemoroiliac dissection when biopsy of the SLN is positive. When biopsy of the SLN is negative for metastatic disease, no further surgical therapy is immediately indicated. With negative SLN, 5-year survival was 90%. When SLN alone was involved, 5-year survival was 70%. Five-year survival was 50% with both SLN and other inguinal nodes involved. When iliac metastases were also present, 3-year survival was 20%.