Targeting IL-13 with tralokinumab normalizes type 2 inflammation in atopic dermatitis both early and at 2 years.

BACKGROUND: Tralokinumab is a monoclonal antibody that specifically neutralizes interleukin (IL)-13, a key driver of skin inflammation and barrier abnormalities in atopic dermatitis (AD). This study evaluated early and 2-year impacts of IL-13 neutralization on skin and serum biomarkers following tralokinumab treatment in adults with moderate-to-severe AD. METHODS: Skin biopsies and blood samples were evaluated from a subset of patients enrolled in the Phase 3 ECZTRA 1 (NCT03131648) and the long-term extension ECZTEND (NCT03587805) trials. Gene expression was assessed by RNA sequencing; protein expression was assessed by immunohistochemistry and immunoassay. RESULTS: Tralokinumab improved the transcriptomic profile of lesional skin by Week 4. Mean improvements in the expression of genes dysregulated in AD were 39% at Week 16 and 85% at 2 years with tralokinumab, with 15% worsening at Week 16 with placebo. At Week 16, tralokinumab significantly decreased type 2 serum biomarkers (CCL17/TARC, periostin, and IgE), reduced epidermal thickness versus placebo, and increased loricrin coverage versus baseline. Two years of tralokinumab treatment significantly reduced expression of genes in the Th2 (IL4R, IL31, CCL17, and CCL26), Th1 (IFNG), and Th17/Th22 (IL22, S100A7, S100A8, and S100A9) pathways as well as increased expression of epidermal differentiation and barrier genes (CLDN1 and LOR). Tralokinumab also shifted atherosclerosis signaling pathway genes (SELE, IL-37, and S100A8) toward non-lesional expression. CONCLUSION: Tralokinumab treatment improved epidermal pathology, reduced systemic markers of type 2 inflammation, and shifted expression of key AD biomarkers in skin towards non-lesional levels, further highlighting the key role of IL-13 in the pathogenesis of AD. CLINICAL TRIAL REGISTRATION: NCT03131648, NCT03587805.

Long-term safety and effectiveness of roflumilast cream 0.3% in adults with chronic plaque psoriasis: A 52-week, phase 2, open-label trial.

BACKGROUND: Efficacy and/or safety profiles limit topical psoriasis treatments. OBJECTIVE: Evaluate long-term effects of once-daily roflumilast cream 0.3% in patients with psoriasis. METHODS: In this open-label phase 2 trial, adult patients (N = 332) with psoriasis who completed the phase 2b parent trial or were newly enrolled applied roflumilast once-daily for 52 weeks. Safety and effectiveness were assessed. RESULTS: Overall, 244 patients (73.5%) completed the trial; 13 patients (3.9%) discontinued due to adverse events (AEs) and 3 (0.9%) due to lack of efficacy. Twelve patients (3.6%) reported treatment-related AEs; none were serious. ≥97% of patients had no irritation. No tachyphylaxis was observed with 44.8% of the patients achieving Investigator Global Assessment (IGA) Clear or Almost Clear at Week 52. LIMITATIONS: Intertriginous-IGA and Psoriasis Area and Severity Index (PASI) were not evaluated in all patients. CONCLUSIONS: In this long-term trial, once-daily roflumilast cream was well-tolerated and efficacious up to 64 weeks in patients in the earlier trial, suggesting it is suitable for chronic treatment, including the face and intertriginous areas.

Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis.

BACKGROUND: Prurigo nodularis is a chronic, debilitating, and severely pruritic neuroimmunologic skin disease. Nemolizumab, an interleukin-31 receptor alpha antagonist, down-regulates key pathways in the pathogenesis of prurigo nodularis. METHODS: In this phase 3, double-blind, multicenter, randomized trial, we assigned adults with moderate-to-severe prurigo nodularis to receive an initial 60-mg dose of nemolizumab followed by subcutaneous injections of 30 mg or 60 mg (depending on baseline weight) every 4 weeks for 16 weeks or matching placebo. The primary end points were an itch response (a reduction of ≥4 points on the Peak Pruritus Numerical Rating Scale [PP-NRS; scores range from 0 to 10, with higher scores indicating more severe itch]) and an Investigator's Global Assessment (IGA) response (a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4] and a reduction from baseline to week 16 of ≥2 points). There were five key secondary end points. RESULTS: A total of 274 patients underwent randomization; 183 were assigned to the nemolizumab group, and 91 to the placebo group. Treatment efficacy was shown with respect to both primary end points at week 16; a greater percentage of patients in the nemolizumab group than in the placebo group had an itch response (56.3% vs. 20.9%; strata-adjusted difference, 37.4 percentage points; 95% confidence interval [CI], 26.3 to 48.5), and a greater percentage in the nemolizumab group had an IGA response (37.7% vs. 11.0%; strata-adjusted difference, 28.5 percentage points; 95% CI, 18.8 to 38.2) (P<0.001 for both comparisons). Benefits were observed for the five key secondary end points: itch response at week 4 (41.0% vs. 7.7%), PP-NRS score of less than 2 at week 4 (19.7% vs. 2.2%) and week 16 (35.0% vs. 7.7%), and an improvement of 4 or more points on the sleep disturbance numerical rating scale (range, 0 [no sleep loss] to 10 [unable to sleep at all]) at week 4 (37.2% vs. 9.9%) and week 16 (51.9% vs. 20.9%) (P<0.001 for all comparisons). The most common individual adverse events were headache (6.6% vs. 4.4%) and atopic dermatitis (5.5% vs. 0%). CONCLUSIONS: Nemolizumab monotherapy significantly reduced the signs and symptoms of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT04501679; EudraCT number, 2019-004789-17.).

Minocycline 1.5% foam for the topical treatment of moderate to severe papulopustular rosacea: Results of 2 phase 3, randomized, clinical trials.

BACKGROUND: Efficacious topical medications for rosacea are needed. FMX103 1.5% is a novel topical minocycline foam that may have therapeutic benefits in treating rosacea while minimizing systemic adverse effects due to its topical route of delivery. OBJECTIVE: To determine the efficacy, safety, and tolerability of 12 weeks of treatment with FMX103 1.5% topical minocycline foam for papulopustular rosacea. METHODS: Two 12-week, phase 3, randomized, multicenter, double-blind, vehicle-controlled, 2-arm studies were performed in patients with moderate to severe papulopustular rosacea. RESULTS: Participants who received FMX103 1.5%, versus control individuals treated with vehicle, exhibited a significantly greater reduction in the number of inflammatory lesions (FX2016-11: -17.57 vs -15.65; P = .0031; FX2016-12: -18.54 vs -14.88; P < .0001) and higher rates of Investigator Global Assessment treatment success (FX2016-11: 52.1% vs 43.0%; P = .0273; FX2016-12: 49.1% vs 39.0%; P = .0077). No serious treatment-related treatment-emergent adverse events occurred. LIMITATIONS: The generalizability of these data from a controlled clinical trial should be examined in a real-world setting. CONCLUSIONS: FMX103 1.5% was efficacious for moderate to severe papulopustular rosacea and maintained a favorable safety profile.

Three-Day Field Treatment with Ingenol Disoxate (LEO 43204) for Actinic Keratosis: Cosmetic Outcomes and Patient Satisfaction from a Phase II Trial.

Objective: To report cosmetic outcomes and patient satisfaction with ingenol disoxate (LEO 43204) used in a once-daily, three-day field treatment regimen in patients with actinic keratosis. Design: This was a phase II, multicenter, open-label trial (ClinicalTrials.gov: NCT02305888) involving 20 trial sites in the United States. Participants: Patients with between five and 20 clinically typical actinic keratoses lesions on the full face/250cm2 on the chest, 25cm2 to 250cm2 on the scalp, or 250cm2 on the trunk/extremities were included. Measurements: The assessment methods in this study included the examination of global photo-damage at Week 8; a cosmetic outcome questionnaire to evaluate the overall appearance and feel of the skin following treatment at Week 8; and a treatment satisfaction questionnaire for medication (TSQM) to evaluate patient satisfaction with treatment at Week 8. Results: Treatment adherence was high, with 97 percent of patients overall applying the full three-day regimen. Global photo-damage improvement was seen in 66, 69, and 72 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. Improved overall appearance of the treatment area was reported by 95, 97, and 80 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. In addition, overall feel of the treatment area was reported as improved by 92, 95, and 70 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. Overall, the mean scores for all four treatment satisfaction questionnaires for medication domains were high in each treatment group, ranging from 66.7/100 to 91.3/100. In particular, mean scores for global satisfaction were 73.9/100, 79.7/100, 66.7/100 for the face/chest, scalp, and trunk/extremities groups, respectively. Conclusion: Actinic keratosis field treatment with ingenol disoxate provided favorable cosmetic benefits and high treatment satisfaction.

Three-day Field Treatment with Ingenol Disoxate (LEO 43204) for Actinic Keratosis: A Phase II Trial.

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of ingenol disoxate gel using a once-daily, three-day field treatment regimen in patients with actinic keratosis. DESIGN: This was a Phase II, multicenter, open-label trial (clinicaltrials.gov: NCT02305888). SETTING: The study was conducted in 20 trial sites in the United States. PARTICIPANTS: Participants included patients with 5 to 20 clinically typical actinic keratosis lesions on the full face/chest (250cm2), scalp (25-250cm2), or the trunk/extremities (250cm2). MEASUREMENTS: We measured incidence of dose-limiting events based on local skin responses. Percentage reduction in actinic keratosis lesion count from baseline, complete clearance, and partial clearance (≥75%) of actinic keratosis lesions were assessed at Week 8. RESULTS: Nine of 63 (14.3%) patients in the face/chest group reported dose-limiting events; zero of 63 patients in the scalp group reported dose-limiting events; and 11 of 62 (17.7%) patients in the trunk/extremities group reported dose-limiting events. Mean composite local skin response scores peaked at Day 4, then rapidly declined, reaching or approaching baseline levels by Week 4. Less than five percent of patients reported severe adverse events; the most common treatment-related adverse events were application site pain and pruritus. The reduction in actinic keratosis lesion count was 78.9, 76.3, and 69.1 percent for the face/chest, scalp, and trunk/extremities groups, respectively. Complete clearance was achieved in 36.5, 39.7, and 22.6 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. Partial clearance was achieved in 71.4, 65.1, and 50.0 percent of patients in the face/chest, scalp, and trunk/extremities groups, respectively. CONCLUSION: Ingenol disoxate demonstrated adverse events and local skin reaction profiles similar to results seen in trials evaluating shorter two-day regimens and was effective in patients with actinic keratosis. These data support the use of ingenol disoxate gel for actinic keratosis field treatment.

Results of a Phase 2, Randomized,Vehicle-Controlled Study Evaluating the Efficacy,Tolerability, and Safety of Daily or Twice Daily SB204 for the Treatment of Acne Vulgaris.

OBJECTIVE: This randomized, double-blind, placebo-controlled, Phase 2 study compared efficacy, tolerability, and safety of SB204 once or twice daily to vehicle in the treatment of acne vulgaris. METHODS: Eligible subjects were to be between 12 and 40 years old, have facial acne vulgaris with 25 to 70 non-inflammatory lesions, 20 to 40 inflammatory lesions, no more than 2 nodules, and a baseline Investigator's Global Assessment (IGA) score of moderate or severe. The co-primary efficacy endpoints were the absolute change in inflammatory and non-inflammatory lesion counts and IGA success rate (baseline to week 12). Safety assessments included reported adverse events (AEs), physical examinations, and laboratory testing. Tolerability was evaluated by the investigators based on the occurrence and severity of erythema, scaling, dryness, pruritus, and burning/stinging. RESULTS: A total of 213 subjects were randomized: 27 subjects to vehicle once daily; 29 subjects to vehicle twice daily; 53 subjects to SB204 2% twice daily; 52 subjects to SB204 4% once daily; and 52 subjects to SB204 4% twice daily. When compared to vehicle, treatment with all 3 SB204 regimens significantly reduced the absolute inflammatory lesion count and SB204 4% once daily reduced the absolute non-inflammatory lesion count. Treatment with SB204 4% once daily demonstrated a significant reduction in percent inflammatory lesions by week 4. There were no significant differences in the IGA success rates between groups at the end of treatment. All treatment regimens of SB204 were found to be safe and well tolerated. CONCLUSIONS: When compared to vehicle, SB204 2% and SB204 4% significantly decreased the absolute inflammatory lesion count and SB204 4% once daily also significantly decreased the absolute non-inflammatory lesion count in subjects with acne vulgaris treated for 12 weeks. Treatment with SB204 2% and 4% was found to be safe and well tolerated. J Drugs Dermatol. 2016;15(12):1496-1502.

Non-obligatory role of prostaglandin D2 receptor subtype 1 in rosacea: laropiprant in comparison to a placebo did not alleviate the symptoms of erythematoelangiectaic rosacea.

Erythematotelangiectatic rosacea shares facial flushing features with those seen after niacin. This study was performed to test the hypothesis whether prostaglandin D2 (PGD2) receptor subtype 1 antagonist (laropiprant) will improve the symptoms of rosacea. The purpose of this study was to evaluate the effect of laropiprant 100 mg administered once daily for 4 weeks on the signs and symptoms of erythematotelangiectatic rosacea. Subjects received laropiprant 100 mg once-daily (n = 30) or placebo (n = 30) for 4 weeks. The primary pharmacodynamics endpoint was change in Clinician's Erythema Assessment (CEA) score from baseline to week 4. The patient self-assessment (PSA) was a secondary endpoint. Laropiprant was generally well tolerated in this study for the primary endpoint of change in CEA score from Baseline to Week 4, the least-squares mean of change from baseline to visit 4/week 4 was -3.7 and -3.4 for placebo and laropiprant (100 mg), respectively. The least-squares mean difference (placebo minus laropiprant) with 90% confidence interval of change in CEA score from baseline to visit 4/week 4 was estimated as -0.3 (-1.6, 1.0). For the secondary endpoint, the least-squares mean difference (placebo minus laropiprant) with 90% confidence interval of change from baseline to visit 4/week 4 was estimated as -0.7 (-7.7, 6.4) for PSA total score, -4.5 (-14.2, 5.3) for PSA emotion score, -1.3 (-7.8, 5.3) for PSA symptoms score, and 3.6 (-4.3, 11.4) for PSA functioning score. Laropiprant administered once daily for 4 weeks was generally well tolerated in this population of subjects with rosacea. However, there were no clinically meaningful changes in the primary endpoint of CEA given that the response to laropiprant could not be differentiated from that to placebo. There was also no clinically meaningful change in the secondary endpoint, PSA. A DP1 antagonist is not likely to be effective in rosacea.

Paradoxical proepileptic response to NMDA receptor blockade linked to cortical interneuron defect in stargazer mice.

Paradoxical seizure exacerbation by anti-epileptic medication is a well-known clinical phenomenon in epilepsy, but the cellular mechanisms remain unclear. One possibility is enhanced network disinhibition by unintended suppression of inhibitory interneurons. We investigated this hypothesis in the stargazer mouse model of absence epilepsy, which bears a mutation in stargazin, an AMPA receptor trafficking protein. If AMPA signaling onto inhibitory GABAergic neurons is impaired, their activation by glutamate depends critically upon NMDA receptors. Indeed, we find that stargazer seizures are exacerbated by NMDA receptor blockade with CPP (3-[(R)-2-carboxypiperazin-4-yl]-prop-2-enyl-1-phosphonic acid) and MK-801, whereas other genetic absence epilepsy models are sensitive to these antagonists. To determine how an AMPA receptor trafficking defect could lead to paradoxical network activation, we analyzed stargazin and AMPA receptor localization and found that stargazin is detected exclusively in parvalbumin-positive (PV (+)) fast-spiking interneurons in somatosensory cortex, where it is co-expressed with the AMPA receptor subunit GluA4. PV (+) cortical interneurons in stargazer show a near twofold decrease in the dendrite:soma GluA4 expression ratio compared to wild-type (WT) littermates. We explored the functional consequence of this trafficking defect on network excitability in neocortical slices. Both NMDA receptor antagonists suppressed 0 Mg (2) (+)-induced network discharges in WT but augmented bursting in stargazer cortex. Interneurons mediate this paradoxical response, since the difference between genotypes was masked by GABA receptor blockade. Our findings provide a cellular locus for AMPA receptor-dependent signaling defects in stargazer cortex and define an interneuron-dependent mechanism for paradoxical seizure exacerbation in absence epilepsy.

Significance of N-methyl-D-aspartate (NMDA) receptor-mediated signaling in human keratinocytes.

Increasing data suggest that glutamate might act as a cell-signaling molecule in non-neuronal tissues such as the skin. Here we demonstrate the presence of functional N-methyl-D-aspartate (NMDA)-type glutamate receptors in human keratinocytes. NMDA receptor expression strongly reflects the degree of cell-to-cell contact. Wounding polarizes the expression of NMDA receptors in keratinocytes involved in re-epithelialization, and the process of re-epithelialization is inhibited by NMDA receptor activation. We also demonstrate that squamous cell carcinomas lack NMDA receptors. Our data suggest that Ca2+ entry through NMDA receptors influences the cycle of keratinocyte proliferation, differentiation, and migration during epithelialization. Moreover, NMDA receptor activation might play a role in contact-mediated inhibition of growth, a process that is absent during neoplastic pathology. This receptor may serve as a pharmacological target for modulating keratinocyte behavior and treating cutaneous disorders.

Objective changes in brow position, superior palpebral crease, peak angle of the eyebrow, and jowl surface area after volumetric radiofrequency treatments to half of the face.

BACKGROUND: Radiofrequency application through a proprietary device has recently been used for facial tissue tightening. Uniform volumetric heating of the dermis is created by passage of electrical current, while protection of the epidermis is maintained by concurrent cryogen cooling. OBJECTIVE: To objectively quantify the effectiveness of volumetric radiofrequency application on the face, we treated 10 patients on the left side of the face with radiofrequency and evaluated the changes in brow position, superior palpebral crease, angle of the eyebrow, and jowl surface area. METHODS: Uniform treatments were applied at 134 J/cm(2) to the left side of the forehead and 1 cm past midline, at 115 J/cm(2) to the left side of temple and cheeks, and at 97 J/cm(2) to the left side of the jaw line and inferior postauricular surface. Patients were evaluated at monthly intervals up to 3 months with digital photography. Morphologic changes were evaluated with the "measuring tool" and "angle tool" of the Mirror Suite imaging system for aligned frontal-view photographs (for eyebrow position, superior palpebral crease elevation, and eyebrow angle changes) and the "outline tool" for aligned oblique-view photographs (for jowl surface area changes). RESULTS: At the end of 3 months on the side that was treated, patients exhibited on average 4.3 mm of brow elevation and 1.9 mm of superior palpebral crease elevation along the midpupillary line and an average of 2.4 mm of brow elevation along the lateral canthal line. There was no significant improvement of brow elevation along the lateral canthal line on the contralateral side. The peak angle of the ipsilateral eyebrow became slightly more acute by an average of 4.5 degrees after treatments. Moreover, the jowls on the lower part of the face, displayed a mean decrease of 22.6% in surface area after treatments. The nontreated side displayed a lack of eyebrow angle and jowl surface area changes. CONCLUSIONS: The application of radiofrequency to the face provides quantifiable changes. The brow along the midpupillary line is elevated to a greater degree than the lateral brow. This is consistent with acute angle changes seen in the eyebrow. Improvements in the lower part of the face with radiofrequency application can be quantified by demonstrating a decrease jowl surface. Moreover, these measurement techniques can be useful tools for evaluating other treatment parameters with radiofrequency application.

Venous malformations in blue rubber bleb nevus syndrome: variable onset of presentation.

Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder characterized by discrete venous malformations of varying size and appearance that are present on the skin and within the gastrointestinal tract. The characteristic cutaneous lesions consist of deep-blue, soft, rubbery blebs, which are easily compressible. A serious complication is gastrointestinal bleeding. Because venous malformations were described historically as cavernous hemangiomas, the lesions of BRBNS were also inappropriately called hemangiomas in the literature. We describe 3 cases to delineate the venous malformations of BRBNS and to highlight their variable onset of presentation and progression. In one case, a venous malformation was noted during a prenatal ultrasound evaluation at 5 months gestation. The other 2 cases demonstrated a lack of the classic cutaneous lesions at birth. BRBNS consists of multiple venous malformations, rather than hemangiomas as described. Subcutaneous venous malformations may occasionally be the sole presenting finding in patients with this unusual syndrome, and may be evident even in the prenatal period.

Lack of difference in the rates of hypopigmentation with 90-microsecond pulsed and longer dwell time carbon-dioxide laser resurfacing.

BACKGROUND: Hypopigmentation is an adverse outcome associated with carbon-dioxide (CO(2)) laser resurfacing. A 90-microsecond pulse produces a more favorable postoperative course of healing, erythema, and pain compared with a 900-microsecond dwell time. The rate of hypopigmentation after 90-microsecond pulsed CO(2) resurfacing may also be reduced. To date, there have been no comprehensive reports on the effect of varying pulse duration on the occurrence of hypopigmentation. OBJECTIVE: We sought to investigate the relationship between pulse duration and the occurrence of hypopigmentation after CO(2) laser resurfacing. METHODS: We conducted a retrospective review of 447 consecutive patients who were treated with a 90-microsecond pulsed CO(2) laser (n = 229) or a continuous wave CO(2) laser with a modifiable dwell time (100-950 microseconds, n = 218). Follow-up ranged from 8 to 61 months (median: 27). RESULTS: A series of 4 threshold dwell times (range: 90-950 microseconds) were used to divide patients into 2 treatment groups (above and below) at each threshold. The rates of hypopigmentation between groups were similar (range: 6.37%-9.09%) and serial chi-square testing revealed no statistical differences between groups for each dwell time tested (P < 1.0). CONCLUSION: No significant relationship between pulse duration and the occurrence of hypopigmentation was observed.

Preliminary study of fine changes in the duration of dynamic cooling during 755-nm laser hair removal on pain and epidermal damage in patients with skin types III-V.

BACKGROUND AND OBJECTIVES: The use of the long-pulsed 755-nm alexandrite laser has been an effective tool in hair removal. A dynamic cooling device (DCD) is commonly used with this laser in order to minimize epidermal damage. No studies have examined how fine changes in DCD duration may affect comfort and epidermal damage during laser hair removal. This study was designed to determine what effect, changes in the duration of dynamic cooling would have on pain and epidermal damage with laser hair removal (755 nm alexandrite) in patients with darker skin types. STUDY DESIGN/MATERIALS AND METHODS: Ten volunteers with Fitzpatrick skin types III-V were enrolled. A 755-nm alexandrite laser with a pulse duration of 3 milliseconds and equipped with a DCD was used with the 12 mm spot size on matched treatment sites. We compared cryogen spurt durations of 0, 20, 40, 60, 80, and 100 milliseconds on pain and epidermal changes. The spray delay was set at 1 millisecond. Pain rating scales and epidermal changes (skin sloughing, hyperpigmentation, hypopigmentation and scarring) were assessed. RESULTS: Overall a decrease in pain was seen with increases in spurt duration. A spurt duration of 20 milliseconds was beneficial for pain reduction in all patients. Longer spurt durations were associated with additional pain relief especially when geographic spacing of pulses was maximized to prevent thermal build-up. In regards to epidermal protection, most patients benefited with shorter cryogen durations of 20-60 milliseconds. There was little advantage with longer spurt durations. Some patients treated at higher fluences without cooling had no detectable side effects. CONCLUSIONS: Increasing DCD spurt duration in laser hair removal provides its strongest benefit in the area of pain reduction, particularly in type V patients. Increasing cryogen spurt durations above a protective threshold shows no significant benefit in terms of epidermal protection. Changing the spurt duration may not be as important in some patients with darker skin types.

Calciphylaxis with peau d'orange induration and absence of classical features of purpura, livedo reticularis and ulcers.

Calciphylaxis is an ill-defined syndrome that is commonly associated with chronic renal failure. Its heterogeneous clinical features include painful livedo reticularis-like purpuric patches and plaques, vesicles, irregularly shaped ulcers, and black eschars. Despite demonstration of extensive vascular arteriolar calcification in this syndrome, its exact pathogenesis remains unknown. Here, we report a case of calciphylaxis presenting with indurated plaques without the usual clinical picture of livedo reticulate purpura, ulcers or necrotic eschars. This case provides an opportunity to review the clinical spectrum of calciphylaxis and to discuss the therapeutic approaches and pathogenesis of this syndrome from deep intra-wall vascular calcification to the resulting infarctions of adjacent tissues.

Hot pop brown spot: erythema Ab igne induced by heated popcorn.

Erythema ab igne is caused by chronic heat exposure and presents with reticulated pigmentation. Although various causes of erythema ab igne have been reported, in the United States, its incidence has been declining due to the advent of central heating. When seen, it is usually in the setting of local applications of a heated source, such as a hot water bottle, to treat muscular or arthritic pains. We report a novel cause of erythema ab igne occurring in a patient with chronic arthritic pains. This patient applied popcorn kernels, heated in a microwave, to his right wrist and knee for 30 minutes at a time for over four months.