Mpox virus and coinfections: An approach to rapid diagnosis.

We report a case of a 42-year-old immunocompromised (human immunodeficiency virus [HIV], CD4 count 86 cells/µL) Black male who presented with fever, oropharyngeal candidiasis, and phimosis, followed by eruption of umbilicated papulovesicles most concentrated on the face. The patient was diagnosed with Mpox (MPXV, formerly monkeypox), herpes simplex virus 1 (HSV1), varicella-zoster virus (VZV), and late latent syphilis. Tzanck smear of a Mpox lesion proved a useful and rapidly obtained pertinent negative test, lacking the typical changes of HSV/VZV (multinucleation, margination, and molding). A biopsy specimen showed viral changes consistent with both Mpox (ballooning degeneration and multinucleated keratinocytes) and herpesvirus (multinucleated epithelial giant cell within a zone of follicular necrosis). Lesion PCR was positive for HSV1 and MPXV, and negative for HSV2 and VZV. Immunohistochemistry was positive for VZV and orthopoxvirus. Empiric treatment for HSV/VZV in patients with suspected or confirmed Mpox should be considered for patients with HIV or other immunocompromised patients. It is important to recognize that MPXV, HSV, and VZV may all be present and difficult to distinguish clinically. More than one test modality (PCR, H&E, immunohistochemistry, and Tzanck) and multiple lesion samples may be required to thoroughly evaluate widespread papulovesicular eruptions, especially in immunocompromised patients.

Increased CD69+CCR7+ circulating activated T cells and STAT3 expression in cutaneous lupus erythematosus patients recalcitrant to antimalarials.

BACKGROUND: Antimalarials are first-line systemic therapy for cutaneous lupus erythematosus (CLE). While some patients unresponsive to hydroxychloroquine (HCQ) alone benefit from the addition of quinacrine (QC), a subset of patients is refractory to both antimalarials. METHODS: We classified CLE patients as HCQ-responders, HCQ+QC-responders, or HCQ+QC-nonresponders to compare immune profiles. Immunohistochemistry, immunofluorescence, and qRT-PCR were used to characterize inflammatory cells and cytokines in lesional skin. RESULTS: Immunohistochemistry showed that CD69+ T cells were higher in HCQ+QC-nonresponders compared to HCQ- and HCQ+QC-responders (p < 0.05). Immunofluorescence further identified these cells as CD69+CCR7+ circulating activated T cells. Myeloid dendritic cells were significantly higher in HCQ+QC-responders compared to both HCQ-responders and HCQ+QC-nonresponders. Plasmacytoid dendritic cells were significantly increased in HCQ-responders compared to HCQ- and HCQ+QC-nonresponders. No differences were found in the number of autoreactive T cells, MAC387+ cells, and neutrophils among the groups. CLASI scores of the HCQ+QC-nonresponder group positively correlated with CD69+CCR7+ circulating activated T cells (r = 0.6335, p < 0.05) and MAC387+ cells (r = 0.5726, p < 0.05). IL-17 protein expression was higher in HCQ+QC-responders compared to HCQ-responders or HCQ+QC-nonresponders, while IL-22 protein expression did not differ. mRNA expression demonstrated increased STAT3 expression in a subset of HCQ+QC-nonresponders. CONCLUSION: An increased number of CD69+CCR7+ circulating activated T cells and a strong correlation with CLASI scores in the HCQ+QC-nonresponders suggest these cells are involved in antimalarial-refractory skin disease. STAT3 is also increased in HCQ+QC-nonresponders and may also be a potential target for antimalarial-refractory skin disease.

Diagnosing muscle disease in a cohort of classic dermatomyositis patients seen at a rheumatologic dermatology outpatient clinic.

BACKGROUND: Existing criteria to improve the probability of capturing dermatomyositis (DM) include muscle biopsy but little is known about whether less invasive diagnostic procedures may be just as useful. OBJECTIVE: We aimed to determine whether skin biopsy, electromyography, or magnetic resonance imaging of the involved muscle could be done in lieu of muscle biopsy. METHODS: Two hundred and seventy-five patients were reviewed to investigate the presence of cutaneous and muscle disease, their timing in relation to diagnosis, and results of skin biopsies, muscle biopsies, magnetic resonance imaging, and electromyography. RESULTS: Of the cases with findings consistent with DM on muscle biopsy, 65% were in agreement with diagnostic features on electromyography or magnetic resonance imaging. Results of skin and muscle biopsies supported DM in 67% of patients who underwent both procedures. LIMITATIONS: A limited number of patients had muscle biopsies. CONCLUSION: In the presence of DM-specific skin findings, less invasive procedures may be sufficient to diagnose DM and guide its management.

Cutaneous lupus concerns from the patient perspective: a qualitative study.

OBJECTIVE: There is a need to identify concerns unique to patients with cutaneous lupus erythematosus (CLE), which may not be captured by current common-practice dermatological quality-of-life tools. This study formally characterises what bothers patients with CLE about their disease by conducting semistructured, qualitative interviews. METHODS: Sixteen patients with CLE were interviewed about how their cutaneous findings impact their daily life. Each interview was transcribed, coded and categorised for recurrent themes. Current CLE activity and damage were also assessed by the Cutaneous Lupus Activity and Severity Index tool. RESULTS: Responses were categorised into six themes, including Fear of Disease Progression, Unwanted Attention, Self-Consciousness, Physical Signs/Symptoms, Emotional Symptoms and Functional Decline. The most commonly reported themes were Self-Consciousness, mentioned by 13 of 16 (81.3%) patients, Physical Symptoms, mentioned by 12 of 16 (75%), and then Fear of Disease Progression, by 11 of 16 (68.8%). Frequently mentioned physical signs/symptoms included erythema, itch, dyspigmentation, scar and alopecia. The physical signs/symptoms were categorised as activity signs/symptoms, damage signs and other. For activity signs, erythema was mentioned most frequently (5 of 16), then scale (2 of 16). For activity symptoms, itch was mentioned most frequently (6 of 16), then pain (5 of 16). For damage signs, dyspigmentation was mentioned most frequently (4 of 16), followed by scarring (3 of 16). Patients less than 60 years old were more likely to report emotional symptoms than older patients (p<0.05), but there was no significant variation in frequency of reported themes between race, sex or subtype of CLE. CONCLUSIONS: These patient experiences and resultant themes elucidated by this study are worth noting in future standardised estimations of the quality of life of patients with CLE. Additionally, the concerns shown by these interviews are important topics for providers to discuss when evaluating patient disease progression.

The CLASI, a validated tool for the evaluation of skin disease in lupus erythematosus: a narrative review.

Cutaneous lupus erythematosus (CLE) can present with or without features of systemic lupus erythematosus (SLE), with estimates of the incidence of isolated skin disease almost equaling the incidence of those with systemic disease. However, despite the impact CLE has on a patient's quality of life (QoL), there has been no US Food and Drug Administration (FDA) approved treatment for the disease in the past 50 years. In addition, patients with skin predominant LE are often excluded from clinical SLE trials. In the rare trials that include patients with skin predominant LE, disease activity and progression in the skin are often difficult to evaluate using multi-organ outcome measures. The need for new therapies for CLE and the lack of focus on skin outcomes has led to the development of the Cutaneous Lupus Disease Area and Severity Index (CLASI), a validated organ-specific outcome measure that is not only responsive to change in disease activity and damage but also correlated to changes in a patient's QoL. This paper will emphasize the extensive validation studies performed in developing the CLASI, as well as the importance of clinical trials using the CLASI to address the need for improved therapies for patients with lupus skin manifestations.

The effects of immunostimulatory herbal supplements on autoimmune skin diseases.

The use of herbal supplements that promise to improve immune health has gained popularity among dermatology patients. However, there is little to no evidence that herbal supplements improve dermatologic conditions. Several in vitro and in vivo studies have shown that Spirulina platensis, Aphanizomenon flos-aqua, Chlorella, Echinacea, and alfalfa activate immune cells via certain cytokines and chemokines. Case reports suggest the association of ingesting immunostimulatory herbs and the clinical onset or flares of diseases characterized by an exaggerated immune response such as lupus erythematosus, dermatomyositis, and autoimmune blistering disorders. Therefore, it is imperative to investigate the prevalence of herbal supplement use in this patient population. In addition, in vitro studies should examine the underlying mechanisms by which herbs stimulate immune pathways that are already overactive in autoimmune patients.

Evaluating change in disease activity needed to reflect meaningful improvement in quality of life for clinical trials in cutaneous lupus erythematosus.

BACKGROUND: Outcome measures of clinical trials in cutaneous lupus erythematosus (CLE) should reflect clinically meaningful improvement in disease activity, as measured by the Cutaneous Lupus Disease Area and Severity Index activity score (CLASI-A). OBJECTIVE: We aimed to define the degree of improvement in disease activity meaningful to a patient's quality of life. METHODS: The change in the CLASI-A in 126 patients needed to predict meaningful change in QoL, as defined by the Emotions and Symptoms subscales of the Skindex-29, was evaluated by linear regression models. RESULTS: In patients with an initial CLASI-A of ≥8, a 42.1% or ≥7-point and a 31.0% or ≥5-point decrease in CLASI-A predicts meaningful improvement in the Emotions and the Symptoms subscales, respectively. LIMITATIONS: This is a retrospective study of prospectively collected data at a single site. CONCLUSIONS: A CLASI-A score of ≥8 for trial entry allows for inclusion of patients with milder disease where CLASI-A improvement by ≥50% is clinically significant and meaningful.

Cutaneous Lupus Erythematosus Patients With a Negative Antinuclear Antibody Meeting the American College of Rheumatology and/or Systemic Lupus International Collaborating Clinics Criteria for Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a disorder that is heterogeneous and can be difficult to diagnose. One hallmark of the disease is the presence of antinuclear antibodies (ANAs), a feature that has been incorporated into multiple classification criteria over the years. In this study, we used a database of patients with cutaneous lupus erythematosus (CLE) to determine how many had a negative ANA and met criteria for SLE using the American College of Rheumatology (ACR) and/or Systemic Lupus International Collaborating Clinics (SLICC) criteria. METHODS: We used a database of 301 biopsy-proven CLE patients that contained information including ANA status and the presence of features of SLE. The database was searched for patients who had a negative ANA result and whether or not they met SLE criteria using the ACR and/or SLICC criteria. RESULTS: Of the 301 patients with biopsy-proven CLE and a known ANA, 111 had a negative ANA test (36.9%) and 27 had an ANA test that fluctuated (33.3%). In all, 20 ANA-negative patients met SLE criteria (18.0%), and 12 patients with a fluctuating ANA test met SLE criteria (44.4%). Of all patients who had either a negative or fluctuating ANA result and who met criteria for SLE (n = 32), 27 patients had involvement of ≥1 organ system other than skin (84.4%), and 13 patients had involvement of ≥2 organ systems other than skin (40.6%). CONCLUSION: Our results show that an ANA is not always present in patients with systemic disease. This fact should be taken into consideration when devising SLE classification criteria to be used for clinical trials.

Adverse Events With the Use of rhBMP-2 in Thoracolumbar and Lumbar Spine Fusions: A 9-Year Institutional Analysis.

STUDY DESIGN: Retrospective chart review. OBJECTIVE: To describe the adverse outcomes associated with the use of rhBMP-2 in thoracolumbar and lumbar fusions. SUMMARY OF BACKGROUND DATA: rhBMP-2 has been increasingly used in spinal fusions over the past decade. Early studies reported that the use of rhBMP-2 is associated with decreased operative time, blood loss, and pain scores, as well as improved fusion rates. Recent investigations have shown rhBMP-2 to be associated with various complications occurring at incidences ranging from 0% to 100%. METHODS: Using the institutional electronic medical records, we retrospectively reviewed all patients between January 2002 and September 2010 that underwent thoracolumbar and lumbar spine fusion with BMP. Patient demographics, operative, and outcome/complication information was collected. RESULTS: A total of 547 patient charts were reviewed with a mean follow-up time of 17 months. Mean age was 58 years. Forty-one percent of patients had undergone previous spine surgery. Thirty-nine percent of patients had a PLIF/TLIF, 29% underwent a PLF, and 20% an ALIF. No relevant differences in the patient characteristics and complications were identified between the various surgical approaches. For all approaches, having undergone a previous spine surgery was associated with increased incidence of radiculitis, reoperation, and pseudoarthrosis (P=0.005, 0.0008, 0.05, respectively) as compared with those without previous spine surgery. Being a current smoker at the time of operation was associated with increased rate of radiculitis (P=0.03) as compared with nonsmokers. CONCLUSIONS: The use of rhBMP-2, in this study, had an incidence of radiculitis, pseudoarthrosis, and reoperation that was similar to the rates in historical controls without rhBMP-2. Complications do not differ by surgical approach, but are more likely in current smokers and those undergoing revision surgery. A prospective study is warranted to further delineate the adverse event profile of rhBMP-2 and the variables that are likely to affect it (ie, type of surgery, carrier, and dose).

Urological complications following use of recombinant human bone morphogenetic protein-2 in anterior lumbar interbody fusion: presented at the 2012 Joint Spine Section Meeting: clinical article.

OBJECT: The goal of this study was to compare the urological complications in patients after anterior lumbar interbody fusion (ALIF) with and without the use of recombinant human bone morphogenetic protein-2 (rhBMP-2). METHODS: The authors retrospectively reviewed the medical records of all patients who underwent ALIF with and without rhBMP-2 between January 2002 and August 2010. Patient demographic, operative, and complication information was analyzed. Male patients who underwent ALIF between L-4 and S-1 were contacted to assess postoperative urological complications. RESULTS: Of the 110 male patients who underwent ALIF and were included in this study, 59 were treated with rhBMP-2 and 51 did not receive rhBMP-2. The mean follow-up duration was 17.5 months for the rhBMP-2 group and 30.8 months for the control group. No difference was found regarding the total number of urological complications in the rhBMP-2 group versus the control group (22% vs 20%, respectively; p = 1.0) or for retrograde ejaculation specifically (8% vs 8%, respectively; p = 1.0). CONCLUSIONS: In this study, the use of rhBMP-2 with ALIF surgery was not associated with an increased incidence of urological complications and retrograde ejaculation when compared with control ALIF without rhBMP-2. Further prospective analyses that specifically look at these complications are warranted.