Non-scarring alopecia of lupus erythematosus: A comprehensive review.

BACKGROUND: Although non-scarring alopecia (NSA) is a frequent clinical finding in patients with systemic lupus erythematosus (SLE), it has been poorly described in the literature. It is considered a nonspecific sign in the current classification of skin lesions of LE. The aim of this study was to give an updated overview of the spectrum of NSA in LE patients, with emphasis on the clinical significance thereof. METHOD: We conducted a review of the English literature using the PubMed-Medline database using the keywords "Alopecia" + "Lupus erythematosus". Publications describing LE patients with NSA were included. RESULTS: Data for 237 patients from 27 publications were analyzed. Ninety-one patients had diffuse NSA, 43 had patchy NSA, 83 had lupus hair, 3 had alopecia of dermal cutaneous LE, and 17 had alopecia of linear and annular lupus panniculitis of the scalp. Patients with diffuse/patchy NSA and lupus hair shared the following features: strong association with systemic activity of LE, subtle clinical/trichoscopic signs of inflammation, histological aspect consistent with lesions specific to cutaneous LE, high likelihood of response to SLE therapy, and absence of progression to scarring alopecia. Association with SLE was rare in patients with dermal cutaneous LE or linear and annular lupus panniculitis of the scalp, and skin-directed therapies were most often effective. One patient of each subtype progressed to scarring alopecia. DISCUSSION: Diffuse/patchy NSA and lupus hair may represent a topographic variation of a single entity specific for LE. Prospective studies are warranted to further document the clinical significance of this manifestation.

Lupus erythematosus: Significance of dermatologic findings.

Herein, the different skin manifestations in patients with lupus erythematosus are reviewed, and their diagnostic, pathogenic and prognostic relevance are discussed, as well as their impact on therapeutic choices. The so-called specific lesions of LE result from an autoimmune pathomechanism and they allow diagnosis of LE by simple clinicopathological correlation since the findings are characteristic. They include the classic acute, subacute and chronic variants, characterised microscopically by interface dermatitis; the dermal variants of lupus, such as tumid lupus, displaying dermal perivascular lymphocytic infiltrate with mucin deposition under the microscope, and lupus profundus, in which lymphocytic lobular panniculitis progressing to hyaline fibrosis is found. Antimalarials are the treatment of choice for patients with specific LE lesions. The presence of some dermatological signs is the result of thrombotic vasculopathy. Their recognition allows the identification of lupus patients at increased cardiovascular risk and with a worse overall prognosis. Those signs include reticulated erythema on the tip of the toes, splinter hemorrhages, atrophie blanche, pseudo-Degos lesions, racemosa-type livedo, anetoderma, ulceration and necrosis. Those clinical manifestations, often subtle, must be recognised, and if present, patients should be treated with antiplatelet drugs. Finally, neutrophilic cutaneous lupus erythematosus includes a few entities that suggest that autoinflammatory mechanisms might play a key role in certain lupus manifestations. Among those entities, it is very important to diagnose neutrophilic urticarial dermatosis, which can mimic a classic lupus flare, because it is characterised by rash with joint pain, but immunosuppressants are not helpful. Dapsone is the treatment of choice.

[Clinical heterogeneity of poikilodermatous mycosis fungoides: A retrospective study of 12 cases]. / Hétérogénéité clinique du mycosis fongoïde poïkilodermique : étude rétrospective de 12 cas.

INTRODUCTION: Poikilodermatous mycosis fungoides is a rare and indolent clinical variant of mycosis fungoides (MF). It can be difficult to distinguish from poikilodermatous parapsoriasis, a group of chronical dermatoses that may sometimes progress to MF. We aimed to specify the clinical, histopathological and developmental features of these entities by means of a retrospective study of 12 cases followed in our center. PATIENTS AND METHODS: We identified cases of poikiloderma for which a diagnosis of MF or parapsoriasis was made by the physician. Photographs and histological slides were reviewed, and a final diagnosis of MF was made if the International Society for Cutaneous Lymphoma criteria for the diagnosis of early MF were fulfilled. RESULTS: Twelve patients were included, 10 of whom met of the MF criteria. 5 patients had large poikilodermatous patches or thin, well-defined plaques ; 3 patients had the same lesions associated with classical MF lesions ; finally, 4 patients had widespread ill-defined erythematous lesions in a net-like pattern, described as parakeratosis variegata, including 3 MF. 2 patients with well-defined lesions (one associated with classical MF lesions) progressed to the tumoral stage whereas none of the patients with parakeratosis variegata presented such progression. A total of 5 patients had a high skin phototype (IV and V). Two patients had squamous cell carcinoma on poikilodermatous lesions. DISCUSSION: Our study suggests that poikilodermatous MF covers a heterogeneous clinical spectrum comprising on one hand a presentation of delimited lesions sharing classical MF risk of progression, and on the other, an entity similar to parakeratosis variegata, an entity overlooked in the French nomenclature, which was particularly benign in our small series, raising the question of its affiliation to the MF group. This question merits further investigation in a larger-scale study.

[Generalized granuloma annulare: A clinicopathological study]. / Granulome annulaire généralisé : étude anatomoclinique.

BACKGROUND: Granuloma annulare (GA) is a benign granulomatous skin disorder that is generalized (GGA) in 15 % of cases. Although many case reports describe a relationship between GGA and systemic diseases, few large series have been published, and their association is debated. We present herein a series of GGA in order to describe their clinical and histological features. PATIENTS AND METHODS: We included all biopsy-proven cases of GA presenting at the dermatopathology laboratory of Strasbourg where generalized (i.e. over 10 lesions). Clinical features were obtained from patients' medical files. RESULTS: We included 35 GGA, with a sex ratio of 0.5. The mean age was 54 years. Lesions were annular or non-annular in equal measure and were symptomatic in 25 % of cases. Most patients (77 %) had an associated disease, already known in 60 % of cases, including dyslipidemia (27 %), diabetes mellitus (20 %), immunosuppressive drugs (17 %), atopy (17 %), auto-immune disease (17 %), hematological disease (14 %), and cancer (9 %). Histological analysis revealed the predominant pattern to be interstitial (54 %) rather than palisading (20 %), having no correlation with clinical type. Eosinophils were frequent (46 %) in GA but were not correlated with systemic disease or drug taking. Among the 40 % of patients treated, 50 % had a successful outcome on topical corticosteroids, doxycycline, antimalarial drugs or phototherapy. DISCUSSION: GGA differs from localized GA, which is mostly associated with an already known systemic disease, whether metabolic, infectious or neoplastic, uncorrelated with clinical or histological features, and screening is necessary.

[Acute generalized pustular bacterid followed by Sweet's syndrome and erythema nodosum]. / Pustulose aiguë généralisée post-streptococcique suivie d'un syndrome de Sweet et d'un érythème noueux.

INTRODUCTION: Streptococcal infections can cause various skin manifestations related to the direct action of the offending organism itself or to a reactional mechanism. Reactional manifestations are less well known and understood, and they include generalized acute pustulosis belonging to the spectrum of neutrophilic dermatoses. We report a case of generalized acute pustulosis followed by Sweet syndrome and erythema nodosum occurring after a streptococcal infection. PATIENTS AND METHODS: A 60-year-old woman was consulting for a diffuse pustular rash after a throat infection, with high levels of anti-streptolysin (337 U/L) and anti-streptodornase (2560 U/L). The biopsy showed folliculitis and a neutrophilic infiltrator of the dermis, and bacteriological and mycological cultures were sterile. The patient then developed papules evoking Sweet syndrome followed by nodules typical of erythema nodosum after 20 days. A favourable outcome was achieved under colchicine. DISCUSSION: Generalized acute pustulosis is a form of neutrophilic dermatosis whose mechanisms, area predilection and treatment are poorly known. The clinical presentation of this patient was initially typical and the secondary progression to lesions like those in Sweet syndrome is consistent with the pathophysiological continuity and overlap of these entities.

[Tattoo hypersensitivity reaction in a patient receiving combined BRAF and MEK inhibitors]. / Hypersensibilité retardée aux tatouages induite par un traitement combiné anti-BRAF/anti-MEK.

INTRODUCTION: For inflammation of a tattoo occurring decades after its creation, sarcoidosis should be considered first of all. Two case of extremely delayed hypersensitivity tattoo reaction have been recently reported in patients treated with BRAF and MEK inhibitors. We report a similar new case strongly suggesting a specific effect of this drug combination. PATIENTS AND METHODS: A 58-year-old man bearing 20-year-old tattoos was treated with dabrafenib and trametinib for advanced melanoma. A painful erythematous swelling appeared on all the patient's tattoos two months later, while his general tolerance of the treatment was poor. Skin biopsy demonstrated perivascular lympho-histiocytic infiltrate without granuloma, but with prominent pigment-loaded macrophages. Inflammatory signs quickly regressed after drug discontinuation. DISCUSSION: Great similarity exists between this new case and the first reported case, in which a female patient presented painful infiltration of old tattoos following repeated reintroduction of dabrafenib and trametinib in a setting of advanced melanoma. The immunomodulatory properties BRAF/MEK inhibition may enhance loss of tolerance to tattoo ink, accounting for the extremely long time to reaction. This third case militates in favour of a specific drug-induced reaction, of which patients with tattoos should be informed when anti-BRAF/MEK therapy is being considered.

[Hyperpigmentation]. / Hyperpigmentations.

The key diagnostic tool for hyperpigmentation is histopathology, which may be accompanied by certain laboratory tests. Hyperpigmentation may result from excess melanin (hypermelanosis), cutaneous iron deposits (hemosiderosis), cutaneous carotene deposits (carotenoderma), or cutaneous deposits of a substance not normally found in the skin (dyschromia). The different types of hypermelanosis may be classified as either localised or generalised. The former generally correspond to skin tumours and may form a cutaneous expression of complex syndromes, which most notably include cardiac abnormalities, or to pigmented forms of inflammatory and/or infectious dermatoses. Diffuse hypermelanosis is frequently a sign of systemic disease, generally metabolic or endocrine disease, or else it may result from pharmaceutical therapy. Herein we review the various causes of hyperpigmentation and the corresponding therapy.

Lyme borreliosis and other tick-borne diseases. Guidelines from the French scientific societies (II). Biological diagnosis, treatment, persistent symptoms after documented or suspected Lyme borreliosis.

The serodiagnosis of Lyme borreliosis is based on a two-tier strategy: a screening test using an immunoenzymatic technique (ELISA), followed if positive by a confirmatory test with a western blot technique for its better specificity. Lyme serology has poor sensitivity (30-40%) for erythema migrans and should not be performed. The seroconversion occurs after approximately 6 weeks, with IgG detection (sensitivity and specificity both>90%). Serological follow-up is not recommended as therapeutic success is defined by clinical criteria only. For neuroborreliosis, it is recommended to simultaneously perform ELISA tests in samples of blood and cerebrospinal fluid to test for intrathecal synthesis of Lyme antibodies. Given the continuum between early localized and disseminated borreliosis, and the efficacy of doxycycline for the treatment of neuroborreliosis, doxycycline is preferred as the first-line regimen of erythema migrans (duration, 14 days; alternative: amoxicillin) and neuroborreliosis (duration, 14 days if early, 21 days if late; alternative: ceftriaxone). Treatment of articular manifestations of Lyme borreliosis is based on doxycycline, ceftriaxone, or amoxicillin for 28 days. Patients with persistent symptoms after appropriate treatment of Lyme borreliosis should not be prescribed repeated or prolonged antibacterial treatment. Some patients present with persistent and pleomorphic symptoms after documented or suspected Lyme borreliosis. Another condition is eventually diagnosed in 80% of them.

Lyme borreliosis and other tick-borne diseases. Guidelines from the French Scientific Societies (I): prevention, epidemiology, diagnosis.

Lyme borreliosis is transmitted en France by the tick Ixodes ricinus, endemic in metropolitan France. In the absence of vaccine licensed for use in humans, primary prevention mostly relies on mechanical protection (clothes covering most parts of the body) that may be completed by chemical protection (repulsives). Secondary prevention relies on early detection of ticks after exposure, and mechanical extraction. There is currently no situation in France when prophylactic antibiotics would be recommended. The incidence of Lyme borreliosis in France, estimated through a network of general practitioners (réseau Sentinelles), and nationwide coding system for hospital stays, has not significantly changed between 2009 and 2017, with a mean incidence estimated at 53 cases/100,000 inhabitants/year, leading to 1.3 hospital admission/100,000 inhabitants/year. Other tick-borne diseases are much more seldom in France: tick-borne encephalitis (around 20 cases/year), spotted-fever rickettsiosis (primarily mediterranean spotted fever, around 10 cases/year), tularemia (50-100 cases/year, of which 20% are transmitted by ticks), human granulocytic anaplasmosis (<10 cases/year), and babesiosis (<5 cases/year). The main circumstances of diagnosis for Lyme borreliosis are cutaneous manifestations (primarily erythema migrans, much more rarely borrelial lymphocytoma and atrophic chronic acrodermatitis), neurological (<15% of cases, mostly meningoradiculitis and cranial nerve palsy, especially facial nerve) and rheumatologic (mostly knee monoarthritis, with recurrences). Cardiac and ophtalmologic manifestations are very rarely encountered.

[Multifocal chalazodermic amyloidosis: The concept of immunoglobulinemic elastopathy]. / Chalazodermie amyloïde multifocale. Le concept d'élastopathie immunoglobulinémique.

INTRODUCTION: Impairment of dermal elastic tissue occurs in different entities associated with immunoglobulins or immunoglobulin-derived protein-secreting clonal plasma cell proliferations, such as amyloid elastosis, anetodermic nodular amyloidosis or monoclonal gammopathy-associated cutis laxa. We report a case of cutaneous immunoglobulinemic amyloidosis revealed by a unique chalazodermic presentation and we review elastic tissue impairment in patients with monoclonal gammopathies. OBSERVATION: A 67-year-old woman consulted for non-infiltrated anetodermic lesions on the upper left quadrant of her abdomen present for ten years. She also had a chalazodermic plaque with abnormal skin wrinkling and laxity in her right axilla. Biopsies revealed deep dermal and subcutaneous amyloid deposits. Immunohistochemistry with lambda light chain was positive. Orcein staining and electron microscopy showed extensive elastolysis. The patient presented no signs of systemic involvement, but a very small amount of monoclonal IgGλ gammopathy was detected during follow-up. DISCUSSION: This is a unique chalazodermic presentation of immunoglobulinemic amyloidosis that does not fit into a clearly-defined nosological setting. It highlights the complex interactions between immunoglobulin-derived proteins, including light and heavy chains, and elastic tissue components, leading to different types of impairment of the latter. We therefore suggest the unifying concept of immunoglobulinemic elastopathy, underscoring the need to screen for monoclonal gammopathy in patients presenting elastic tissue impairments.

[Suprapubic Nicolau syndrome following subcutaneous injection of glatiramer acetate]. / Dermite livédoïde de Nicolau sus-pubienne après injections sous-cutanées d'acétate de glatiramère.

BACKGROUND: Subcutaneous glatiramer acetate, commercialized under the name of Copaxone®, is licensed for the treatment of relapsing multiple sclerosis. Its major adverse effects are skin reactions at the injection site. Nicolau syndrome is a rare but serious iatrogenic accident. Herein we report a case seen in a setting of change of dosage and administration rate of Copaxone®. PATIENTS AND METHODS: A 64-year-old woman, treated since 2010 with daily sub-cutaneous injections of Copaxone® 20mg/L, reported the appearance of a painful, indurated and erythematous plaque in the suprapubic area following changeover to 40mg/mL injections three times weekly. The suprapubic injections were continued and ugly greyish spots with stellate purpuric borders appeared. Fournier gangrene was ruled out by means of a soft tissue scan. DISCUSSION: We report this latest case of Nicolau syndrome to alert readers to the non-exceptional nature of this complication associated with use of glatiramer acetate, particularly at a dosage of 40mg/L injections three times weekly. In our case, onset of Nicolau syndrome appears to have been favored by continued injection in areas already showing inflammation. Re-injection of the drug in these areas should thus be proscribed.

Overall survival and oncological outcomes after partial nephrectomy and radical nephrectomy for cT2a renal tumors: A collaborative international study from the French kidney cancer research network UroCCR.

BACKGROUND: Partial nephrectomy (PN) is recommended as first-line treatment for cT1 stage kidney tumors because of a better renal function and probably a better overall survival than radical nephrectomy (RN). For larger tumors, PN has a controversial position due to lack of evidence showing good cancer control. The aim of this study was to compare the results of PN and RN in cT2a stage on overall survival and oncological results. METHOD: A retrospective international multicenter study was conducted in the frame of the French kidney cancer research network (UroCCR). We considered all patients aged≥18 years who underwent surgical treatment for localized renal cell carcinoma (RCC) stage cT2a (7.1-10cm) between 2000 and 2014. Cox and Fine-Gray models were performed to analyze overall survival (OS), cancer specific survival (CSS) and cancer-free survival (CFS). Comparison between PN and RN was realized after an adjustment by propensity score considering predefined confounding factors: age, sex, tumor size, pT stage of the TNM classification, histological type, ISUP grade, ASA score. RESULTS: A total of 267 patients were included. OS at 3 and 5 years was 93.6% and 78.7% after PN and 88.0% and 76.2% after RN, respectively. CSS at 3 and 5 years was 95.4% and 80.2% after PN and 91.0% and 85.0% after RN. No significant difference between groups was found after propensity score adjustment for OS (HR 0.87, 95% CI: 0.37-2.05, P=0.75), CSS (HR 0.52, 95% CI: 0.18-1.54, P=0.24) and CFS (HR 1.02, 95% CI: 0.50-2.09, P=0.96). CONCLUSION: PN seems equivalent to RN for OS, CSS and CFS in cT2a stage kidney tumors. The risk of recurrence is probably more related to prognostic factors than the surgical technique. The decision to perform a PN should depend on technical feasibility rather than tumor size, both to imperative and elective situation. LEVEL OF EVIDENCE: 4.