Life threatening rickettsiosis and the role of hemophagocytic lymphohistiocytosis syndrome (HLH): Case report of a 21-year-old woman.

Hemophagocytic lymphohistiocytosis (HLH) syndrome is an uncontrolled activation of macrophages, causing multiorgan dysfunction. The prognosis depends on the cause and the delay of diagnosis and treatment. Several infections can cause HLH, including rickettsia, a gram-negative bacterium. The diagnosis of rickettsia is based on clinical signs, including fever, headache, rash and sometimes tick bite site. The importance of an early diagnosis of rickettsia is the key. We present a case of rickettsia infection complicated with severe HLH occurring in a 21-year-old woman. The diagnosis was confirmed by serology 4 weeks after admission. She was treated with immunoglobulin, corticosteroids, and doxycycline with a favorable outcome.

Omalizumab in the treatment of bullous pemphigoid resistant to first-line therapy: a French national multicentre retrospective study of 100 patients.

BACKGROUND: Interest in the use of omalizumab to treat bullous pemphigoid (BP) in the event of resistance or contraindication to conventional therapies is currently based on limited evidence. OBJECTIVES: To assess the effectiveness and safety of omalizumab in BP and to identify predictive factors in response to treatment. METHODS: We conducted a French national multicentre retrospective study including patients with a confirmed diagnosis of BP treated with omalizumab after failure of one or several treatment lines. We excluded patients with clinically atypical BP, as per Vaillant's criteria. The criteria for clinical response to omalizumab were defined according to the 2012 international consensus conference. Anti-BP180-NC16A IgE enzyme-linked immunosorbent assay was performed on sera collected before initiating omalizumab, when available. RESULTS: Between 2014 and 2021, 100 patients treated in 18 expert departments were included. Median age at diagnosis was 77 years (range 20-98). Complete remission (CR) was achieved in 77% of patients, and partial remission in an additional 9%. CR was maintained 'off therapy' in 11.7%, 'on minimal therapy' in 57.1%, and 'on non-minimal therapy' in 31.2%. Median time to CR was 3 months (range 2.2-24.5). Relapse rate was 14%, with a median follow-up time of 12 months (range 6-73). Adverse events occurred in four patients. CR was more frequently observed in patients with an increased serum baseline level of anti-BP180-NC16A IgE (75% vs. 41%; P = 0.011). Conversely, urticarial lesions, blood total IgE concentration or eosinophil count were not predictive of CR. Patients with an omalizumab dosage > 300 mg every 4 weeks showed a similar final outcome to those with a dosage ≤ 300 mg every 4 weeks, but control of disease activity [median 10 days (range 5-30) vs. 15 days (range 10-60); P < 0.001] and CR [median 2.4 months (range 2.2-8.2) vs. 3.9 months (range 2.3-24.5); P < 0.001] were achieved significantly faster. CONCLUSIONS: We report the largest series to date of BP treated by omalizumab and confirm its effectiveness and safety in this indication. Serum baseline level of anti-BP180-NC16A IgE may predict response to treatment.

Intramuscular capillary-type hemangioma: Diagnosis, treatment, and outcomes. A French multicentric retrospective study of 66 cases.

PURPOSE: Intramuscular capillary-type hemangiomas (ICTHs) are rare entities, belonging to the group of intramuscular "hemangiomas." The diagnosis remains challenging. We aimed to assess the diagnostic criteria, treatments and outcomes of ICTHs. METHODS: This retrospective study collected all cases of ICTH followed up in 9 French hospital centers, reviewed by an adjudication expert group. RESULTS: Among 133 patients screened, 66 with ICTH were included. The median age of patients at diagnosis was 28.0 years, interquartile range (21.0---36.0). The lesion, mainly presenting as a gradually increasing mass (83.9%), was painless (88.9%) and was located in the head and neck (42.4%). MRI (available in all cases) mainly revealed a well-delineated lesion, isointense to the muscle on T1-weighted images, with enhancement after contrast injection; hyperintense on T2-weighted images; and containing flow voids. Among the 66 cases, 59 exhibited typical ICTH features and 7 shared some imaging features with arteriovenous malformations. These latter were larger than typical ICTHs and more painful and appeared on imaging as less well delimited and more heterogeneous tissue masses, with larger tortuous afferent arteries, earlier draining vein opacification and mild arteriovenous shunting. We propose to name these lesions arteriovenous malformation (AVM)-like ICTH. Pathological reports were similar in typical and AVM-like ICTH, showing capillary proliferation with mainly small-size vessels, negative for GLUT-1 and positive for ERG, AML, CD31 and CD34, with low Ki67 proliferation index (<10%), and adipose tissue. The most frequent treatment for ICTH was complete surgical resection (17/47, 36.2%), preceded in some cases by embolization, which led to complete remission. CONCLUSIONS: ICTH can be diagnosed on MRI when it is typical. Biopsy or angiography are required for atypical forms.

Clostridium difficile infection and immune checkpoint inhibitor-induced colitis in melanoma: 18 cases and a review of the literature.

Immunotherapy has become the standard of care for several types of cancer, such as melanoma. However, it can induce toxicity, including immune checkpoint inhibitor-induced colitis (CIC). CIC shares several clinical, histological, biological, and therapeutic features with inflammatory bowel disease (IBD). Clostridium difficile infection (CDI) can complicate the evolution of IBD. We aimed to characterize the association between CDI and CIC in patients treated with anti-CTLA-4 and anti-PD-1 for melanoma. Patients from nine centers treated with anti-CTLA-4 and anti-PD-1 for melanoma and presenting with CDI from 2010 to 2021 were included in this retrospective cohort. The primary endpoint was the occurrence of CIC. The secondary endpoints were findings allowing us to characterize CDI. Eighteen patients were included. Eleven were treated with anti-PD-1, four with anti-CTLA-4, and three with anti-PD-1 in combination with anti-CTLA-4. Among the 18 patients, six had isolated CDI and 12 had CIC and CDI. Among these 12 patients, eight had CIC complicated by CDI, three had concurrent CIC and CDI, and one had CDI followed by CIC. CDI was fulminant in three patients. Endoscopic and histological features did not specifically differentiate CDI from CIC. Nine of 11 patients required immunosuppressive therapy when CDI was associated with CIC. In nine cases, immunotherapy was discontinued due to digestive toxicity. CDI can be isolated or can complicate or reveal CIC. CDI in patients treated with immunotherapy shares many characteristics with CDI complicating IBD. Stool tests for Clostridium difficile should be carried out for all patients with diarrhea who are being treated with immunotherapy.

Asymmetric periflexural exanthem of childhood and influenza virus infection.

Asymmetric periflexural exanthem of childhood (APEC) is a self-limited disease characterized by unilateral exanthem. The etiology is unknown, but a viral agent is suspected. Most often there is no formal proof of an associated viral etiology, but several associations between APEC and some viruses have been described. We report a 2-year-old girl with APEC associated with influenza A. This case allows us to provide an additional argument on a probable viral etiology of APEC and a possible etiologic role of influenza A.

Deep cutaneous fungal infections in solid-organ transplant recipients.

BACKGROUND: Deep cutaneous fungal infections (DCFIs) are varied in immunosuppressed patients, with few data for such infections in solid-organ transplant recipients (s-OTRs). OBJECTIVE: To determine DCFI diagnostic characteristics and outcome with treatments in s-OTRs. METHODS: A 20-year retrospective observational study in France was conducted in 8 primary dermatology-dedicated centers for s-OTRs diagnosed with DCFIs. Relevant clinical data on transplants, fungal species, treatments, and outcomes were analyzed. RESULTS: Overall, 46 s-OTRs developed DCFIs (median delay, 13 months after transplant) with predominant phaeohyphomycoses (46%). Distribution of nodular lesions on limbs and granulomatous findings on histopathology were helpful diagnostic clues. Treatments received were systemic antifungal therapies (48%), systemic antifungal therapies combined with surgery (28%), surgery alone (15%), and modulation of immunosuppression (61%), leading to complete response in 63% of s-OTRs. LIMITATIONS: Due to the retrospective observational design of the study. CONCLUSIONS: Phaeohyphomycoses are the most common DCFIs in s-OTRs. Multidisciplinary teams are helpful for optimal diagnosis and management.

Acrodermatitis continua of Hallopeau response to optimized biological therapy.

Acrodermatitis continua of Hallopeau, first described in 1890, is an uncommon variant of pustular psoriasis. It presents as a sterile pustular eruption of the tips of fingers and toes. The condition has a chronic, relapsing course and is often resistant to many anti-psoriatic therapies. In the following case, we present our experience of etanercept use in a 61-year-old man. Although initial therapy with high-dose etanercept achieved a rapid, sustained response and remission, the lesions relapsed a few months into a lower, maintenance dosage. This result prompted the use a second biotherapeutic agent ustekinumab, which resulted in complete remission, but required a higher dosage than recommended with reduced dosing intervals.

Subacute cutaneous lupus erythematosus induced by nivolumab: two case reports and a literature review.

Nivolumab is widely used to treat several late-stage malignancies such as melanoma and non-small-cell lung cancer by inhibiting the interaction between the programmed cell death protein-1 and its ligand. By stimulating an antitumor immune response, it also leads to immune adverse events. Here. we report two cases of subacute cutaneous lupus erythematosus (SCLE) induced by nivolumab. Case 1: a 72-year-old woman with a stage IV melanoma. Two months after nivolumab discontinuation because of autoimmune hepatitis, the patient was in complete remission and pruritic nummular erythematous plaques appeared on the back and arms. Case 2: a 43-year-old man put under nivolumab for a metastatic non-small-cell lung cancer. After two cycles, an annular erythematous eruption appeared on the hands, arms, and chest. The hypothesis of SCLE was confirmed by biopsies showing lymphoid perivascular inflammatory infiltrates, with scarce C3 deposits along the basal layer of the epidermis in patient 2. Both patients tested positive for antinuclear antibodies and anti-SSA antibodies. Lesions were regressive under topical corticosteroids and hydroxychloroquine for the first patient and oral prednisone for the second patient. No systemic involvement was observed. The occurrence of SCLE 2 months after nivolumab discontinuation is evidence that the drug effect is prolonged because of the maintenance of programmed cell death protein-1 reception saturation for months. A causal relationship between SCLE and nivolumab is suggested by (i) the occurrence of SCLE after at least two cycles, (ii) the regression of lesions following treatment with corticosteroids and hydroxychloroquine, and (iii) the fact that it appeared after remission in our first patient.

Search for RASA1 Variants in Capillary Malformations of the Legs in 113 Children: Results from the French National Paediatric Cohort CONAPE.

Patients with an inherited autosomal-dominant disorder, capillary malformation-arteriovenous malformation (CM-AVM), frequently have mutations in Ras P21 protein activator 1 (RASA1). The aims of this study were to determine the prevalence of germline RASA1 variants in a French multicentre national cohort of children, age range 2-12 years, with sporadic occurrence of capillary malformation (CM) of the legs, whatever the associated abnormalities, and to identify genotype-phenotype correlates. DNA was extracted from leukocytes in blood samples, purified and amplified, and all exons of the RASA1 gene were analysed. Among 113 children analysed, 7 had heterozygous variants (6.1%). Four different variants were identified; 2 were new. In children with RASA1 variants, CMs were more frequently bilateral and multifocal. In conclusion, RASA1 variants are rarely found in children with sporadic CM of lower limbs without CM-AVM syndrome. CMs in this study were heterogeneous, and no disease-causing relationship could be proven.

Generalized pruritus in dysmetabolic hyperferritinemia treated by phlebotomy.

This paper describes a case of pruritus caused by dysmetabolic hyperferritinemia treated by multiple phlebotomies. A 63-year-old man was followed for generalized pruritus, which was resistant to the usual treatments. He presented with metabolic syndrome. Physical examination showed only excoriations and lichenification on the skin. The serum ferritin was high at 1043 ng/ml, with transferrin saturation at 67%. The other biological investigations and genetic tests for hemochromatosis were negative. In spite of the dietary measures, the ferritin level was still high (853 ng/ml). Magnetic resonance imaging confirmed hepatic iron overload.The association of hyperferritinemia, hepatic iron overload, and metabolic syndrome led to the diagnosis of dysmetabolic hyperferritinemia. Phlebotomies are an unusual treatment, but because the pruritus and hyperferritinemia were still present, phlebotomy was initiated. After 19 months, the patient reported improvement of his pruritus and normalization of ferritin levels.

Multidisciplinary team meetings in Oncology: first analysis of benefits and evaluation of activity in a Dermatology unit in France.

Improving Multi-Disciplinary Meetings (MDM) is one of the 70 clauses of the French Cancer Plan of 2003-2007. The French High Authority of Health (HAS) and the National Cancer Institute (INCa) have established guidelines to standardize MDM concerning cancer care. No objective assessment of cutaneous cancer (dermato-oncology) MDM has been published yet, despite the growing numbers in the incidence of skin cancers. This study aims to analyze two of our center's MDM concerns: its decisions and its compliance with HAS guidelines. A retrospective study of all skin tumors discussed in MDM held at Amiens University Hospital between 2006-2007 analyzed epidemiological data, MDM decisions (recommendations), and their compliance. 349 MDM conclusion reports concerning 228 patients were analyzed. The cases consisted of 132 melanomas, 27 basal cell carcinomas, 19 squamous cell carcinomas, 5 Merkel cell carcinomas, 8 sarcomas, 16 cutaneous lymphomas, and 21 other tumors. 45.7% of MDM had at least 3 different specialists present. Patients were present in 49.4% of discussions. 88% of the MDMs' recommendations were implemented. More than 94% of these decisions were according to the guidelines. MDM recommendations contributed to: making 13.6% of diagnoses, 74.7% of treatment decisions, 45.6% of investigations requested, and 48.2% of long-term follow-up decisions. Treatment recommendations were: surgery in 50.6% of patients, chemotherapy in 45.0% and radiotherapy in 12.5%. The MDM's therapeutic decisions tended to follow the specialty of the referring physician; e.g. patients were likely to have surgery when referred by a surgeon, etc (p < 0.0001). Dermato-oncology MDM at Amiens University Hospital comply with most of the guidelines, however, patient attendance at MDM, participation of different specialists and the formal function and structure, all have room for improvement.

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome.

Several syndromes manifest as recurrent daily fevers, skin lesions, and multisystem inflammation. We describe 4 patients with early-onset recurrent fevers, annular violaceous plaques, persistent violaceous eyelid swelling, low weight and height, lipodystrophy, hepatomegaly, and a range of visceral inflammatory manifestations. Laboratory abnormalities included chronic anemia, elevated acute-phase reactants, and raised liver enzymes. Histopathologic examination of lesional skin showed atypical mononuclear infiltrates of myeloid lineage and mature neutrophils. Our patients have a distinctive early-onset, chronic inflammatory condition with atypical or immature myeloid infiltrates in the skin. We propose the acronym CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature) syndrome for this newly described disorder, which is probably genetic in origin.

The course of melanoma-associated vitiligo: report of a case.

The appearance of vitiligo-like lesions in patients with malignant melanoma is a well-known yet uncommon phenomenon. This finding is especially reported in patients undergoing immunotherapy with or without chemotherapy for malignant melanoma and is generally believed to be associated with a better prognosis. We report a case of preexisting vitiligo in a 48-year-old man, aggravated after chemo-immunotherapy of pulmonary metastatic melanoma with interferon-alpha, vinblastine and dacarbazine. Skin lesions remained stable after discontinuation of the treatment, and repigmentation heralded the recurrence of metastatic disease. These findings were in favor of vitiligo being a marker of the immunity against melanoma cells and its favorable impact on the prognosis of melanoma patients.