Finger nodules with a papulovesicular hands and feet eruption: a complicated human Orf virus infection.

BACKGROUND: Orf virus (ORFV) is the pathogen responsible for Orf, a zoonotic viral infection that can be spread to humans from sheep and goats. Here, we present a case of human Orf complicated by an immune-related reaction, to raise awareness of this under-recognized disease avoiding unnecessary investigations and overtreatment. CASE REPORT: A 51-year-old woman with no previous medical history presented with a one-week history of three asymptomatic swelling nodules with a grey necrotic center and red outer halo on her index finger. At physical examination there was also a pruritic papulovesicular eruption on her hands and feet. She reported a recent contact with a goat which had a similar nodular lesion in its mouth. A biopsy of the lesions was performed and a diagnosis of Orf complicated by widespread erythema multiforme was made based on the clinical and histopathological features. The lesions spontaneously resolved within the next 2 weeks. CONCLUSIONS: Orf is not very prevalent in our region, so we performed a biopsy of the lesion to guide us toward a diagnosis. However, we should remember that the diagnosis of ecthyma relies on clinical evaluation and epidemiological criteria.

Lyme Neuroborreliosis with Intracranial Hypertension and Erythema Multiforme: A Rare Presentation.

A 9-year-old previously healthy boy presented with high-grade intermittent fever, severe headache associated with neck stiffness for 5 days, rash over trunk and extremities for 4 days, vomiting for 3 days and diplopia for 2 days. There was no history of seizures, abnormal body movements, altered sensorium or focal deficits. On examination, he had maculopapular erythematous rashes over the trunk and extremities and erythema multiforme. He had bilateral abducens nerve palsy and the rest of the cranial nerve, sensory and motor examination was normal. He had neck stiffness and positive Kernig's sign. Fundus examination showed grade 4 papilledema. Cerebrospinal fluid workup revealed elevated opening pressure, lymphocytic pleocytosis, normal protein and glucose levels. Neuroimaging showed features suggestive of intracranial hypertension. Borrelia IgM and IgG antibodies came positive. The uniqueness of our case lies with two rare presenting manifestations of Lyme neuroborreliosis in the same child.

Neuropsychiatric manifestations in an adolescent male with Rowell syndrome.

A 15-year-old boy presented with fever, skin, and oral lesions for 4 weeks. The cutaneous lesions were suggestive of subacute cutaneous lupus erythematosus and erythema multiforme. His clinical, histopathological, and immunological features were indicative of Rowell syndrome and he satisfied the diagnostic criteria of Rowell syndrome proposed by Zeitouni et al. He subsequently developed neurological manifestations and was diagnosed to have neuropsychiatric systemic lupus erythematosus. We report this case for the unusual occurrence of a rare entity like Rowell syndrome in an adolescent male with co-existence of neuropsychiatric systemic lupus erythematosus.

Orofacial granulomatosis and erythema multiforme in an adolescent with Crohn's disease.

The cutaneous manifestations of Crohn's disease are myriad. A 15-year-old girl presented with recurrent lip swelling and eventual development of diarrhea and targetoid macules on the palms, feet, and back. She was finally diagnosed with Crohn's disease in the setting of a clinical presentation and histopathology consistent with orofacial granulomatosis and erythema multiforme. We review the literature and summarize reported occurrences of these cutaneous diseases in children with Crohn's disease.

Epidemiology of ophthalmologic disease associated with erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis in hospitalized children in the United States.

The objective of the current study was to characterize the epidemiology and resource use of U.S. children hospitalized with ophthalmologic disease secondary to erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). We studied children ages 5 to 19 years hospitalized in 2005 in 11 states, encompassing 38% of the U.S. pediatric population. Using International Classification of Diseases, Ninth Revision, Clinical Modification codes, we identified admissions of children with EM, SJS, or TEN and the presence of concurrent ophthalmologic disease, analyzed patient and hospitalization characteristics, and generated age- and sex-adjusted national estimates. We identified 460 children admitted with EM, SJS, or TEN, corresponding to 1,229 U.S. hospitalizations in 2005. Of the children with EM, SJS, or TEN, 60 (13.0%) had ophthalmologic disease, primarily (90.0%) disorders of the conjunctiva. Children with the highest proportions of ophthalmologic disease included those with mycoplasma pneumonia (26.7%), herpes simplex virus (15.6%), upper respiratory infection (13.9%), and lower respiratory infection (13.7%). Individuals with EM, SJS, or TEN and ophthalmologic disease were more likely than those without ophthalmologic disease to receive intensive care unit care (28.3% vs 17.0%, p = 0.03) and to be admitted to a children's hospital (63.3% vs 48.8%, p = 0.03). Ophthalmologic disease was also associated with a significantly longer median length of stay (6.0 days, interquartile range [IQR] 3-9 days vs 3.0 days, IQR 2-6 days, p < 0.001) and median hospital cost ($7,868, IQR $3,539-$17,440 vs $2,969, IQR $1,603-$8,656, p < 0.001). In children with EM, SJS, or TEN, ophthalmologic disease was most common in those with concurrent Mycoplasma pneumoniae and herpes simplex virus infections. Ophthalmologic disease was associated with considerably higher inpatient resource use in this population. Children with EM, SJS, or TEN should be screened and treated early for ophthalmologic disease to prevent morbidity and minimize long-term sequellae.

[Effect of proteflazid on TLRs expression by mononuclear leukocytes of peripheral blood and epithelial cells of mucous membranes and skin in patients with herpes-associated erythema multiforme and erythema annulare centrifugum].

The article reports survey data on 23 patients with erythemas, including 19 patients with herpes-associated erythema multiforme (HAEM) and 4 patients with Darier's erythema annulare centrifugum (DEAC). Patients in the initial state (baseline) and after two weeks of therapy with proteflazid were characterized by measuring the levels of Toll-like receptor (TLR) expression in peripheral blood mononuclear cells (PBMC) and in epithelial cells of the throat and the skin. The TLR expression in PBMC and skin was assessed by flow cytometry with monoclonal antibodies (ICA) (Caltag Laboratories, USA; Hycult Biotech, Netherlands) against relevant antigens. In addition, patients were also characterized by the content of subpopulations of lymphocytes expressing surface markers CD3, CD4, CD8, CD16, CD21, CD23, CD72, CD25, and HLA-DR in the peripheral blood, which was measured by flow cytometry. The therapy with proteflazid in patients with both HAEM and DEAC led to normalization of the level of both T-cell and B-cell immunity, which was manifested by an increase in the total number of lymphocytes, CD3+, CD4+, CD21+, and CD72+. Measurements of the dynamics of TLR expression in the course of immunotherapy showed an increase in the number of TLR 2, 3, 4, 7, 8, and 9 in PBMC (which was especially pronounced for TLR2) and in epithelium of the pharyngeal mucosa and skin (increased expression of TLR3, 7, and 9).

[Lip synechiae after erythema multiforme]. / Synéchies de la muqueuse labiale dans les suites d'un érythème polymorphe.

BACKGROUND: Mucosal erosions in bullous diseases and leading to mucosal sequelae are widely described in toxic epidermal necrolysis (TEN). These complications cause disfigurement and functional impairment. They are more rarely reported in erythema multiforme (EM). We report a case of lip adhesion following EM induced by Mycoplasma pneumoniae. PATIENT AND METHODS: A 12-year-old boy was hospitalized in a paediatric intensive care unit. He had a prominent target skin rash on the palms and soles. Mucosal injury was associated with conjunctivitis, balanitis without dysuria and hyperalgesic stomatitis. M. pneumoniae serology was positive with immunoglobulin M. We made a diagnosis of EM secondary to M. pneumoniae infection. Two months later, the skin lesions had completely disappeared but the patient's mouth opening was limited to 25 mm and he presented bilateral adhesions between the upper and lower lips of 5mm on the right and 8mm on the left resulting in aesthetic and functional damage. DISCUSSION: Mucosal damage and its sequelae have been widely described in TEN. Ophthalmic sequelae are more frequent. A case of labial synechiae secondary to TEN has been reported. In EM, mucosal lesions occur in 100% of cases with a further mucosal problem being present in 50% of patients. Mucosal damage has been reported during EM flares but there are no studies of side-effects after the acute episode. Oral mucosal adhesions can cause cosmetic sequelae, but above all they hinder functional prognosis. These complications must be prevented by making gutters of vestibular deepening and lip movements with maximum mouth opening several times a day, starting as soon as possible. Appropriate pain management should be undertaken to ensure patient comfort and avoid the need for analgesics and restriction of movement. CONCLUSION: Mucosal sequelae exist in EM. Whatever their cause, complications involving the mucosa must be prevented through early, tailored and multidisciplinary treatment. Adequate pain management must not be overlooked.

Reality of drug-induced erythema multiforme: A French pharmacovigilance study.

BACKGROUND: Since the 2002 SCAR study, erythema multiforme (EM), a post-infectious disease, has been distinguished from Stevens-Johnson syndrome (SJS), drug-induced. Nevertheless, EM cases are still reported in the French pharmacovigilance database (FPDB). OBJECTIVES: To describe EM reported in the FPDB and to compare the quality and the characteristics of the reports. METHODS: This retrospective observational study selected all EM cases reported in the FPDB over two periods: period 1 (P1, 2008-2009) and period 2 (P2, 2018-2019). Inclusion criteria were 1) a diagnosis of clinically typical EM and/or validated by a dermatologist; 2) a reported date of onset of the reaction; and 3) a precise chronology of drug exposure. Cases were classified confirmed EM (typical acral target lesions and/or validation by a dermatologist) and possible EM (not-otherwise-specified target lesions, isolated mucosal involvement, doubtful with SJS). We concluded possible drug-induced EM when EM was confirmed, with onset ranging from 5 to 28 days without an alternative cause. RESULTS: Among 182 selected reports, 140 (77%) were analyzed. Of these, 67 (48%) presented a more likely alternative diagnosis than EM. Of the 73 reports of EM cases finally included (P1, n=41; P2, n=32), 36 (49%) had a probable non-drug cause and 28 (38%) were associated with only drugs with an onset time ≤4 days and/or ≥29 days. Possible drug-induced EM was retained in 9 cases (6% of evaluable reports). Etiological work-up was more often performed in period 2 than 1 (53.1% vs 29.3%, P=0.04), and the time to onset from 5 to 28 days was more frequent in period 2 (59.2% vs 40%, P=0.04). CONCLUSIONS: This study suggests that possible drug-induced EM is rare. Many reports describe "polymorphic" rashes inappropriately concluded as EM or post-infectious EM with unsuitable drug accountability subject to protopathic bias.

Multiple finger nodules and an erythematous rash - a case study.

CASE STUDY: A previously well male, 18 years of age, from a rural community, presented with three painful, itchy nodules on the fingers of his left hand, which had been present for 1 week. He had been prescribed amoxicillin clavulanate but presented again when there was no improvement after 4 days of taking antibiotics. Examination revealed three erythematous and umbilicated nodules without any halo, but with a central depression with exudate (Figure 1a). No specific treatment was instituted at this visit. One week later the patient re-presented with new erythematous lesions on the palms and dorsum of his hands. The original three lesions had improved and were drier than previously (Figure 1b, c). The new lesions disappeared after 2 weeks and the original lesions after 4 weeks, without any other treatment.

Patch testing versus interferon-gamma release assay in evaluation of drug eruptions.

Delayed-onset T-cell-mediated cutaneous adverse drug reactions are an uncommon but potentially serious result of medication exposures. Identification of culprit medications is crucial, but clinical diagnosis is often difficult. Patch tests and interferon-gamma release assays (IFNγ-RA) were previously reported as potentially useful ancillary tests, while rechallenges remain the reference standard test. We compared the number of positive test results with patch testing and IFNγ-RA for drugs implicated as possible causes of cutaneous reactions. Fifty-one patients with a suspected cutaneous drug eruption underwent patch testing and IFNγ-RA for suspected drugs. Participants were followed up at least 9 months after the onset of the rash with results compared with the clinical diagnosis. Forty-two patients presented with morbilliform/eczematous eruptions; five were diagnosed with fixed drug eruption (FDE) and four with erythema multiforme. None had positive patch testing to the drugs tested. A total of 8/51 (15.6%) patients had positive reaction by the IFNγ-RA, and an additional 11 (21.6%) patients had borderline results. Positive or borderline results were more likely in patients with FDE (80%) than morbilliform/eczematous eruptions (30.9%) or erythema multiforme (25%). Our study emphasizes the necessity of additional effective ancillary tests in the evaluation of drug eruptions and supports the use of IFNγ-RA for drug testing as a tool for identifying medications associated with cutaneous drug eruptions.

Cutaneous Toxicities Associated with Immune Checkpoint Inhibitors: An Observational, Pharmacovigilance Study.

Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observational pharmacovigilance study using VigiBase, the World Health Organization's global database of individual case safety reports from over 130 member countries (ClinicalTrials.gov, number NCT04898751). We compared adverse event reporting in patients who received immune checkpoint inhibitors (91,323 adverse events) with those of the full reporting database (18,919,358 adverse events). There were 10,933 cases of cirAEs within 51 distinct dermatologic types, with 27 specific eruptions with disproportionate signal represented (information component [IC]025 > 0). Of these 27 eruptions, there were eight cirAEs with n > 100 reports, including vitiligo (IC025 = 4.87), bullous pemphigoid (IC025 = 4.08), lichenoid dermatitis (IC025 = 3.69), erythema multiforme (IC025 = 1.03), toxic epidermal necrolysis (IC025 = 0.95), Stevens‒Johnson syndrome (IC025 = 0.41), drug eruption (IC025 = 0.11), and eczematous dermatitis (IC025 = 0.11). There were differences in time to onset after immune checkpoint inhibitor initiation, with a median of approximately 1 month (erythema multiforme, Stevens‒Johnson syndrome, and toxic epidermal necrolysis), 2 months (drug eruption and eczematous dermatitis), 4 months (lichenoid dermatitis), and 5‒6 months (bullous pemphigoid and vitiligo). CirAEs are diverse, dependent on cancer type, and have distinct and different onset times that are linked to the cirAE subtype.

Mycoplasma pneumoniae-induced rash and mucositis: A new entity.

Mycoplasma pneumoniae is a well-known cause of community-acquired pneumonia, mostly associated with dermatological manifestations especially with mucosal involvement and targetoid cutaneous lesions. For many years, it was considered among the spectrum of erythema multiforme. Recently, some authors have recommended the creation of a new syndrome called "mycoplasma-induced rash and mucositis." This new syndrome has distinct epidemiological, clinical and histological features making it different from drug-induced Stevens-Johnson syndrome, toxic epidermal necrosis and erythema multiforme. Herein, we report two patients with acute Mycoplasma pneumoniae respiratory tract infection presenting severe mucocutaneous lesions in accordance with this new syndrome.

Transient natural killer deficiency in a boy with herpes simplex virus-associated recurrent erythema multiforme.

Erythema multiforme is characterized by itching macules, papules and bullae, symmetrically distributed on the dorsum of the hands. They can follow the administration of several drugs or infections with various agents, and in particular with herpes simplex virus. The recurrent variant is very rare, especially in the paediatric age group. We describe the case of a male adolescent with recurrent erythema multiforme caused by herpes virus and transient natural killer deficiency.