Published in Dermatology News · April 29, 2022 Annual Costs Estimated for Wart Treatment in the U.S. for 2015-2017

Per-patient costs for evaluation and management estimated at $288.28 for cutaneous warts and $431.47 for anogenital warts in 2019

WEDNESDAY, April 27, 2022 (HealthDay News) -- The estimated annual costs were $846 million for cutaneous warts for 2019 in the United States, and costs for anogenital warts were $127 million, according to a research letter published online April 27 in JAMA Dermatology.

Ronald Berna, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues evaluated annual health care utilization and costs associated with common cutaneous and anogenital wart treatments in a retrospective cohort study using the deidentified Optum Clinformatics Database.

On average, for each year from 2017 through 2019, 263,070 individuals with cutaneous warts (mean age, 44 years; 52 percent female) and 28,516 with anogenital warts (mean age, 43 years; 40.7 percent female) were captured. The researchers found that 64.2, 1.8, and 2.2 percent of individuals with cutaneous warts were treated with lesional destruction, intralesional injection, and prescription topical medications, respectively. For anogenital warts, 35.3, 0.6, and 16.5 percent were treated with lesional destruction, intralesional injection, and prescription topical medications, respectively. For 2019, the annual costs were estimated at $846 million and $127 million for cutaneous and anogenital warts, respectively. The per-patient costs were estimated at $288.28 and $431.47 for cutaneous and anogenital warts, respectively.

"Understanding health care utilization for warts provides useful information for anticipatory guidance (e.g., expected number of treatments) and insight into the burden of disease," the authors write.

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Oximetazolina para ptosis palpebral

EYE-OPENING NEWS ABOUT OXYMETAZOLINE

By Warren R. Heymann, MD, FAAD
April 27, 2022
Vol. 4, No. 17

Certain articles have a "wow" factor that immediately impacts practice. In 2007, I recall being impressed by the 2 cases of erythematotelangiectatic rosacea reported by Shanler and Ondo that dramatically improved with the application of oxymetazoline hydrochloride 0.05%. (1) Oxymetazoline had been used for decades to treat nasal decongestion or to "get the red out" of the eyes; I thought the idea was brilliant. I have been recommending it ever since either as the over-the-counter product or the 1% prescription cream formulation released in 2017. (2)

Oxymetazoline is a potent vasoconstrictor that also demonstrates anti-inflammatory properties. It is a direct-acting, imidazoline-type sympathomimetic agonist that is highly selective for the α1A-adrenoceptor and is also a partially selective α2A-receptor agonist. (1) The drug's vasoconstrictive effects have been used to advantage for other dermatological conditions, including post-acne erythema (3,4), erythromelalgia of the knee (5), and hemostasis during dermatologic surgery. (6)

Oxymetazoline 0.1% ophthalmic solution is now available for the treatment of blepharoptosis (drooping of the eyelid, subsequently referred to as ptosis). This commentary will focus on the use of oxymetazoline for ptosis. (I have no financial or any other perceived conflict of interest with RVL Pharmaceuticals, Inc. the distributor of Upneeq.)

Ptosis may be a cosmetic concern but if significant enough, may interfere with vision. I have mild ptosis — people have told me to "wake up" during our conversations. (Sometimes they are correct and I am falling asleep!)

Ptosis is a physical sign, not a diagnosis. Ptosis may be congenital or acquired. Acquired adult ptosis is categorized as 1) aponeurotic (aka involutional; this is the most common form, usually presenting in the 5th-6th decade, most frequently due to dehiscence or disinsertion of the levator aponeurosis; 2) neurogenic (due to disruption of innervation of either the levator muscle or Muller muscle [a small smooth muscle arising from the striated levator muscle along with the aponeurosis] as may be seen with Horner syndrome or 3rd cranial nerve palsy; 3) myogenic (due to an abnormality of levator muscle itself, as seen with myasthenia gravis or myotonic dystrophy; 4) mechanical (secondary to any tumor causing increased eyelid weight, conjunctival scarring, and blepharochalasis); and 5) traumatic (due to direct or indirect injury to the levator muscle). (7) If there is any question about the etiology of ptosis an ophthalmological consultation should be sought.

Oxymetazoline elevates the eyelid by activating α-adrenergic receptors in the Muller muscle. Slonim et al reported the results of 2 industry-sponsored randomized placebo-controlled masked trials that assessed the efficacy of oxymetazoline, 0.1%, eyedrops for ptosis. A total of 304 patients with acquired ptosis to topical oxymetazoline HCl, 0.1%, vs vehicle in 2 trials were randomized. All participants had clinically relevant involutional (aponeurotic) ptosis defined by superior visual field loss and reduced eyelid height. Response to therapy was evaluated at 1 day and 14 days of treatment, and safety was evaluated over 42 days of follow-up. Using Leicester Humphrey Visual Field (HVF) static perimetry as the primary outcome, the authors showed a change in the oxymetazoline treatment arm of 4 to 5 points of superior visual field more than the change in the vehicle arm. The secondary outcome, change in upper eyelid height, increased by less than 0.5 mm in the treatment arm compared with the vehicle arm on day 1 and by 0.67 mm compared with vehicle on day 14.

Oxymetazoline HCl, 0.1%, was generally well tolerated, with no change in visual acuity or intraocular pressure but with somewhat higher rates of punctate keratitis, conjunctival hyperemia, and subjectively blurred vision in the study group. (8,9) In an editorial accompanying the article by Slonim at al, Bradley and Bradly opine; "It is unclear whether a gain of 4 to 5 points of superior visual field, or roughly half a line of points on the Leicester HVF, represents meaningful clinical change. The corresponding less than 1 mm of eyelid elevation produced by oxymetazoline compared with vehicle may also be of marginal clinical benefit. While it is possible that this degree of eyelid elevation yields substantial improvements in visual function and patient self-image, an assessment of health-related quality of life was not included in the study." Additionally, this study did not compare oxymetazoline with surgery, although when compared to historical data, the improvement with oxymetazoline is less than is usually observed with surgical repair. (9)

Wirta et al (with Slonim as senior author) evaluated the safety profile of oxymetazoline 0.1% when administered once daily for 14-84 days to assess treatment-emergent adverse events (TEAE). A total of 568 participants with acquired blepharoptosis were evaluated. The median age was 66 years and 74.8% of participants were female. Overall, 375 participants self-administered oxymetazoline 0.1% to both eyes once/day and 193 self-administered placebo (vehicle) daily. TEAE incidence was similar among participants using oxymetazoline 0.1% (31.2%) or vehicle (30.6%). Nearly all TEAEs were mild-to-moderate, and most were not suspected of being treatment related. Serious TEAEs occurred in four participants receiving oxymetazoline 0.1% and one participant receiving vehicle. Nine and 2 participants in the oxymetazoline 0.1% and vehicle groups, respectively, discontinued due to a TEAE. Ocular TEAEs occurring in ≥2% of participants receiving oxymetazoline 0.1% were punctate keratitis, conjunctival hyperemia, dry eye, blurred vision, instillation site pain, and corneal vital dye staining, with none occurring in >3.5% of participants, allowing the authors to conclude that oxymetazoline for ptosis is safe and well tolerated.

Wirta et al explain that oxymetazoline may affect α-adrenergic receptors expressed elsewhere in the eye (conjunctiva, iris-ciliary structures, aqueous outflow tract) that could explain the adverse reactions of punctate keratitis, conjunctival hyperemia, and dry eye. Finally, oxymetazoline may be associated with transient mydriasis and acute angle closure glaucoma – trials with oxymetazoline excluded such patients. (10)

Dermatologists may encounter ptosis due to localized spread of botulinum toxin when administered for treating glabellar lines. Oxymetazoline may be considered as convenient, rapid, safe, and effective treatment for this adverse reaction to botulinum toxin. (11)

Before prescribing oxymetazoline, I would encourage all to read the package insert. Avoid using the medication in those with a history of acute angle glaucoma and be judicious with its use in hypertensive patients.

I could not resist the temptation. I tried it, but my results were barely perceptible (see below, and please ignore the subconjunctival hemorrhage). Our practice manager, however, was delighted with her results that were observed within an hour (see below, with permission).

Acknowledgement: I thank Lacy L. Sommer, MD, FAAD, for her photographic skills.

Warren R. Heymann, MD, FAAD

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Journal Scan / Research · April 20, 2022 Leukocyte Adhesion and Rolling in Skin With Patient Outcomes After Hematopoietic Cell Transplantation Using Noninvasive Reflectance Confocal Videomicroscopy JAMA Dermatology

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In this prospective single-center cohort study, patients with a history of hematopoietic cell transplantation (HCT) for hematologic cancer underwent noninvasive skin videomicroscopy to quantify leukocyte-endothelial interactions and determine their association with relapse, relapse-free survival, and overall survival. The adherent and rolling leukocytes per hour were able to better predict relapse and survival than the revised Disease Risk Index.
A new method of quantifying leukocyte-endothelial interactions provides more accurate prognostic information than the current best-prediction models for patients with a history of HCT.
– Joshua R. Ortego, MD

Abstract
IMPORTANCE
Hematopoietic cell transplantation (HCT) is a potential cure for hematologic cancer but is associated with a risk of relapse and death. Dynamic biomarkers to predict relapse and inform treatment decisions after HCT are a major unmet clinical need.
OBJECTIVE
To identify a quantitative characteristic of leukocyte-endothelial interactions after HCT and test its associations with patient outcomes.
DESIGN, SETTING, AND PARTICIPANTS
In this prospective single-center cohort study from June 2017 to January 2020, patients of any age, sex, race, and ethnicity who had HCT for hematologic cancer were referred by health care professionals as either suspected of having symptoms or not having symptoms of acute graft-vs-host disease between 25 and 161 days after HCT. Patients underwent noninvasive skin videomicroscopy. Videos of dermal microvascular flow were recorded with a reflectance confocal microscope. Two blinded observers (J.R.P. and Z.Z.) counted leukocytes adherent to and rolling along the vessel wall per hour (A&R). Of 57 enrolled patients, 1 relapsed before imaging and was excluded, resulting in 56 patients included in analyses.
MAIN OUTCOMES AND MEASURES
Relapse of cancer, relapse-free survival, and overall survival.
RESULTS
Among the 56 patients (median age, 59 years; 38 [68%] male) who underwent imaging a median of 40 days after HCT, 21 had high A&R and 35 had low A&R. After correcting for the revised Disease Risk Index, patients with high A&R had higher rates of relapse (hazard ratio [HR], 4.24; 95% CI, 1.32-13.58; P = .02), reduced relapse-free survival (HR, 3.29; 95% CI, 1.26-8.55; P = .02), and reduced overall survival (HR, 3.06, 95% CI, 1.02-9.19; P = .05). These associations were preserved after correcting for possible confounders, steroid treatment, and acute graft-vs-host disease status. In the prognostic adequacy calculation by using Cox models, the new imaging biomarker (A&R) accounted for 82% to 95% of the prognostic information to predict each outcome. By contrast, the best existing clinical predictor routinely available, the revised Disease Risk Index, accounted for 10% to 28% of the prognostic information in the same model.
CONCLUSIONS AND RELEVANCE
In this cohort study, leukocyte-endothelial interactions, visualized directly in skin after HCT, were associated with the patient outcomes of relapse, relapse-free survival, and overall survival. Assessing this dynamic marker could help patients at high risk for relapse who may benefit from interventions, such as early withdrawal of immunosuppression.

JAMA Dermatology
Association of Leukocyte Adhesion and Rolling in Skin With Patient Outcomes After Hematopoietic Cell Transplantation Using Noninvasive Reflectance Confocal Videomicroscopy
JAMA Dermatol 2022 Mar 26;[EPub Ahead of Print], I Saknite, JR Patrinely, Z Zhao, H Chen, A Beeghly-Fadiel, TK Kim, M Jagasia, M Byrne, ER Tkaczyk

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Journal Scan / Research · April 22, 2022 Disproportional Signal of Sexual Dysfunction Associated With Finasteride Use in Young Men With Androgenetic Alopecia Journal of the American Academy of Dermatology

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The authors conducted a pharmacovigilance analysis to investigate the association between finasteride use and sexual dysfunction in men with androgenetic alopecia. A total of 7700 reports of sexual dysfunction associated with finasteride were identified, with 67.9% of reports made between 2015 and 2019. There was a significant disproportionality signal for sexual dysfunction with finasteride versus drugs with a similar mechanism of action (eg dutasteride, tamsulosin, and minoxidil). This discrepancy was driven by men under the age of 45 years and androgenetic alopecia patients.
Finasteride is associated with sexual dysfunction in men, especially those under the age of 45 years and with androgenetic alopecia; however, confounding factors by indication and stimulated reporting likely contribute to the recent increase in incidence reports.

– Katherine M. Stiff, MD

Written by: Steven R. Feldman MD, PhD

Finasteride and sexual dysfunction

Years ago, after an episode of urinary tract infection, I went to see a urologist for, well, you do not want to know, because they do unspeakable things to guys who have urinary tract infections. Anyway, the urologist was also a specialist in managing sexual dysfunction. I was discussing with him how there is very little overlap between dermatology and urology except for the use of finasteride, which we use for alopecia. He said to me with an air of of surprise in his voice, "You use finasteride? Aren't you concerned about the sexual dysfunction side effects?"

At the time, I thought, well, he specializes in sexual dysfunction; so, he probably sees people all day who claim they have sexual dysfunction from finasteride and does not see the ones who do not have that side effect. His perception would be horribly biased by his practice of selecting patients who had a problem. I still thought that there is probably no relationship between finasteride and sexual dysfunction.

Nguyen et al's article describing a signal for sexual dysfunction from finasteride based on spontaneous reports still leaves me feeling as if there is no real signal. If finasteride did cause sexual dysfunction, almost certainly it would do it more with higher doses than with low doses, and I suspect that it would be extraordinarily unlikely for anybody who had sexual dysfunction and was on minoxidil to blame the minoxidil. Therefore, it seems entirely reasonable to me that there would be relatively more reports of sexual dysfunction from finasteride than from minoxidil. I do not see any basis for the authors conclusion, "it is unlikely that confounding factors alone account for the totality of the signal observed–there is likely a true underlying effect albeit not as significant as observed." On the contrary, it seems that confounding factors and reporting biases alone would account for the so-called "signal" that was observed.

It is easy to draw mistaken conclusions from spontaneous reporting of data. That said, when starting patients on finasteride for alopecia, I would warn them of reports of sexual dysfunction. Educating patients about this risk may make the risk more likely (given the nocebo effect), but that is something we probably have to live with, given the potential repercussions of not warning someone who may develop sexual dysfunction.

Abstract

In a recent study by our group, finasteride use was found to be associated with increased reporting of suicidality and depression in young patients with androgenetic alopecia. This previous analysis suggested that the association between finasteride and depression might be mediated by sexual dysfunction, which in men includes erectile dysfunction, diminished libido, and ejaculatory disorders. It is challenging to characterize the association between finasteride use and sexual dysfunction at the population level due to underlying age-related comorbidities causing sexual dysfunction in older men with benign prostatic hyperplasia (BPH) and possible nocebo phenomenon in which a negative outcome occurs due to expectations that an intervention will cause harm, amongst other factors.

Journal of the American Academy of Dermatology

Disproportional signal of sexual dysfunction reports associated with finasteride use in young men with androgenetic alopecia: A pharmacovigilance analysis of VigiBase

J Am Acad Dermatol 2022 Mar 26;[EPub Ahead of Print], DD Nguyen, P Herzog, EB Cone, M Labban, KC Zorn, B Chughtai, S Basaria, DS Elterman, QD Trinh, N Bhojani

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ONE TOKER OVER THE LINE: CLARIFYING TOKER CELL HYPERPLASIA IN ZUSKA DISEASE AND ITS RELATIONSHIP TO HIDRADENITIS SUPPURATIVA

By Warren R. Heymann, MD, FAAD
April 20, 2022
Vol. 4, No.

Don't fret. I had never heard of Zuska disease (ZD) either until I read the article by Torre-Castro et al discussing the "tricky association" of Toker cell hyperplasia (TCH) in ZD. (1) Why should you care? Because it is likely that you have seen — and will continue to see — patients with this disorder and should be aware of this potentially problematic association.

ZD (aka mammillary fistula [MF]) was first reported by Zuska et al in 1951 who described a case series of 5 women (with his wife as the index patient) in what were previously considered nontuberculous breast fistulae. The presumption was that lactiferous ducts became obstructed by squamous metaplasia, resulting in subareolar breast abscesses. The mean age of presentation of ZD is 47 years and smoking is strongly associated with the disease. A rare complication of ZD is squamous cell carcinoma of the breast. (2,3)

Cosman and Al-Refaie were the first to recognize extramammary cutaneous findings in ZD, reporting on 2 women in their forties, with evidence of hidradenitis suppurativa (HS) in the inguinal and axillary regions, respectively. The following are the authors' conclusions: "We present two patients with MF and concurrent acne inversa/HS lesions. These cases raise the question of whether MF might be a manifestation of acne inversa. Despite the ample literature on MF and the very extensive literature on HS, this is a previously unrecognized association, suggesting either that these cases are unusual or that they demonstrate something that has not been seen because it has not been looked for. In its lack of description of associated conditions, the literature contains the implicit assumption that MF is an isolated lesion of the breast. Our cases challenge that assumption, and it remains for surgeons who see MF frequently to confirm or deny the suggested association with acne inversa/HS." (4)

Toker cells (TC) are normal components of skin of the nipple and areola, thought to be derived from epidermally located mammary ductal epithelium. TC are observed in approximately 10% of nipple sections with routine stains and up to 90% of nipple specimens by CK7 staining, with greater numbers of cells located around nipple orifices. TC may be seen as isolated cells, in small clusters, or as gland-like structures. TCH refers to cases in which TC are found in increased numbers (defined as up to 20 single cells or up to 10 glands). The practical issue is in differentiating TCH from it mimic — Paget disease (PD) of the nipple. Paget cells tend to be more pleomorpbic and mitotic figures may be observed, compared to TC which, at most, have mild cytological atypia. In problematic cases, histochemical stains for mucin or immunostains may be needed to differentiate the two. (Paget cells stain with mucin stains such as mucicarmine, while TC are negative. Immunohistochemically, TC stain for CK7, CAM5.2, and EMA; variable staining is seen for ER and PR, and do not show significant staining for HER2, CK20, GCDFP-15, S100 protein, CD138, p53,p63, or CEA. Paget cells similarly stain with CK7, CAM5.2 and EMA and also show variable staining for ER and PR. Most importantly, the vast majority of cases of Paget disease are strongly HER2 positive; this may be considered the most helpful immunostain differentiating PD from TCH.) (5)

DWII image on Zuska disease — JAAD 2009; 60: 539-561.

Torre-Castro presented the case of a 42 year-old smoker with recurrent painful inflammatory lesions of her nipples, presenting as nipple inversion. Biopsies were performed because of the clinical concern for PD. The presence of large pale cells was initially thought to be consistent with PD — further differentiating immunohistochemical stains were performed confirming the correct diagnosis of TCH when the patient provided additional history of having similar inflammatory lesions of her groin and having a sister with HS. (1)

Squamous cell carcinoma (SCC) may be considered the most severe complication of HS — I am still haunted by my examination of a woman I encountered as a first-year dermatology resident. She had a fungating, filiform anal lesion, emanating from her scarred perianal HS, that tracked up to her cervical spine, ultimately causing her demise. The prevalence of SCC associated with HS is approximately 4.6%* and is more common among men. (*SCC complicating HS is considered rare — the reported prevalence seems high in my estimation.) As in other scars that predispose to the development of SCC, presumably chronic irritation and inflammation of HS drive the malignant transformation to SCC; additionally, other potential risk factors for malignant transformation may include human papillomavirus (HPV) infection and tobacco use. (6) I surmise that the cases of SCC of the breast in ZD are essentially the same process.

In my PubMed search (performed Jan. 1, 2021) I cannot find any cases of PD in patients with ZD or HS. Of course, anything can happen. Torre-Castro et al have done dermatologists a service by pointing out how we need to be cognizant of TCH, so patients do not get misdiagnosed as PD in the context of ZD/HS. Such patients have enough to deal with already.

Point to Remember: In all likelihood, Zuska disease is a localized form of hidradenitis suppurativa. Although this may rarely be complicated by squamous cell carcinoma, the development of Paget Disease is yet to be reported. Should Pagetoid cells be observed histologically, Toker cell hyperplasia — a benign condition — must be considered. Mucin and immunohistochemical stains will differentiate the two.

Our expert's viewpoint

Ginette A. Okoye, MD, FAAD
Professor & Chair
Howard University College of Medicine

Mammillary fistula (MF) is likely a manifestation of hidradenitis suppurativa (HS). The demographics, anatomic location, and association with smoking and squamous cell carcinoma (SCC) support this assertion. Although submammary abscesses and sinus tracts are common in HS, involvement of the mammary tissue, especially in the sub-areola area, is less common and should be alarming to the patient and provider. I have several patients with HS and mamillary fistulae. These lesions are not subtle: my patients have sub-areola nodules and/or induration, inverted nipples, overlying peau d'orange, and purulent drainage from the nipple or areola. I refer these patients for urgent mammograms, and I send them to a breast surgeon for excision, if needed. Unfortunately, recurrence is common after excision, especially if the patient is not on concurrent anti-inflammatory therapy. Additionally, the excisions often result in scarring and asymmetry of the breasts, and exacerbation of the dysmorphia that plagues patients living with HS. My ongoing concern is that we could miss a diagnosis of breast cancer in patients with MF given their distorted anatomy, scar tissue, and blunting of our response to the recurrent 'false alarms' seen on their breast exams.

Additionally, Dr. Heymann's commentary highlights the gap in our understanding of the histopathology of hidradenitis suppurativa. Some of the histologic features of HS overlap with SCC (7) and (apparently!) Paget's disease, so building our expertise in the histopathology of HS has important implications. Patients with HS are increasingly undergoing en bloc excisions and de-roofing procedures. I strongly advocate for IRB-approved prospective collection of the discarded tissue from these procedures to help build HS tissue biorepositories. The availability of this tissue (and the associated clinical information) will facilitate observations and research to improve our understanding of this terrible disease. (8)

Torre-Castro J, Haya-Martínez L, Ruffin-Vicente B, Moya-Martínez C, Núñez-Hipólito L, Díaz de la Pinta J, Cullen-Aravena D, Jo-Velasco M, Requena L. Toker cell hyperplasia in Zuska disease: A tricky association. J Cutan Pathol. 2021 Jan;48(1):180-183.
Zuska JJ, Crile G Jr, Ayres WW. Fistulas of lactifierous ducts. Am J Surg. 1951 Mar;81(3):312-7.
Huws AM, Semkin L, Moalla A, Udayasankar S, Holt SDH, Sharaiha YM. Primary squamous cell carcinoma of the breast in association with Zuska's disease. Breast Cancer. 2018 May;25(3):365-369.
Cosman BC, Al-Refaie WB. Mammillary fistula as a manifestation of acne inversa (hidradenitis suppurativa): report of two cases. J Am Coll Surg. 2002 Jun;194(6):829-33.
Torous VF, Schnitt SJ, Collins LC. Benign breast lesions that mimic malignancy. Pathology. 2017 Feb;49(2):181-196.
Chapman S, Delgadillo D III, Barber C, Khachemoune A. Cutaneous squamous cell carcinoma complicating hidradenitis suppurativa: a review of the prevalence, pathogenesis, and treatment of this dreaded complication. Acta Dermatovenerol Alp Pannonica Adriat. 2018 Mar;27(1):25-28.
Dunstan RW et al. Histologic progression of acne inversa/hidradenitis suppurativa: implications for future investigations and therapeutic intervention. Exp Dermatol 2021;30:820-830. DOI 10.1111/exd.14273.
Byrd AS, Dina Y, Okoh UJ, Quartey QQ, Carmona-Rivera C, Williams DW, et al. Specimen collection for translational studies in hidradenitis suppurativa. Sci Rep. 2019 Aug 21;9(1):12207. DOI: 10.1038/s41598-019-48226-w

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Autoinoculation vs 35% Trichloroacetic Acid for Molluscum Contagiosum Journal of the American Academy of Dermatology

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In this randomized controlled study, 124 patients with 5 or more non-genital lesions, clinically diagnosed as molluscum contagiosum, were treated with either a single session of 35% trichloroacetic acid (TCA) or autoinoculation. Autoinoculation was performed by repeatedly piercing a well-formed lesion with an insulin syringe. At 3 months, complete clearance was achieved in 80% of the autoinoculation group compared with 62% of the TCA group. Recurrence at 6 months was lower in the autoinoculation group compared with that in the TCA group (3% vs 40%).
Autoinoculation is an effective treatment for molluscum contagiosum.

– Katherine M. Stiff, MD

Written by: Ashish C. Bhatia MD, FAAD
Written by: Eliot N. Mostow MD, MPH
Written by: Robert T.Brodell MD, FAAD

This small study is important because it speaks of doing less to get an equal to better benefit with no significant side effects! There has been debates for years about whether we should treat these lesions, but I support doing something, rather than letting a child end up with hundreds of lesions (and spreading the lesions to other children as well). This simple idea of "auto inoculation" is puncturing the perilesional and lesional skin five to seven times with a needle from an insulin syringe. Presumably, this puts some of the molluscum virus into the dermis, so that the immune system can finally recognize the virus, which is the reason for the ultimate clearance.

We like simple solutions and would like to keep this idea in our treatment regimen as we await more robust studies.

Abstract

Despite the availability of numerous destructive or immunomodulatory treatment options for molluscum contagiosum (MC), a single universally reliable and effective therapeutic modality is yet to emerge. Autoinoculation is a well-studied treatment modality for warts. Recently Kachhawa et al demonstrated that autoinoculation is a successful treatment modality for MC, which helped in clearance of both local and distant lesions. This prompted us to compare the efficacy of autoinoculation versus tricholoroacetic acid (TCA) in MC.

Journal of the American Academy of Dermatology

A randomized controlled pilot study of autoinoculation versus 35% trichloroacetic acid for the treatment of molluscum contagiosum

J Am Acad Dermatol 2022 Mar 15;[EPub Ahead of Print], D Kachhawa, P Choudhary, S Saraswat, A Lamoria, YR Joshi, C Yadav

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Dutasteride Intralesional Microinjections in Combination With Oral Minoxidil vs Oral Minoxidil Monotherapy in Men With Androgenetic Alopecia Journal of the European Academy of Dermatology and Venereology: JEADV

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In this retrospective single-center study, male patients with androgenetic alopecia were treated with oral minoxidil 1–5 mg daily alone (n = 58) or in combination with intralesional dutaseride microinjections (n = 47). A 2-mL solution comprising 1 mL of dutasteride 0.01% and 1 mL of normal saline was injected per session for 3 months. Observed side-effects were related to oral minoxidil in both groups, and no sexual dysfunction was reported in any participant.
Combination therapy of oral minoxidil plus intralesional dutasteride led to significantly greater improvement at the vertex (P ≤ .001) compared with the outcomes of oral minoxidil monotherapy. Although large-scale and long-term studies are needed, the efficacy of this treatment and relief from the risk of sexual dysfunction may provide an alternative therapeutic option to men concerned about systemic adverse effects of oral 5α-reductase.

– Caroline K. Crabtree, MD

Written by: Paradi Mirmirani MD

Dutasteride, a potent inhibitor of 5-alpha reductase types I and II, has shown to be effective for hair growth in those with androgenetic alopecia. However, the concern for sexual side-effects has many patients and clinicians searching for localized methods of drug delivery to maximize hair growth while avoiding side-effects. Since dutasteride has a large molecular weight and high lipophilicity, cutaneous or follicular penetration of the drug is likely quite limited. Microinjections, or mesotherapy, has been advocated as another strategy for cutaneous, localized drug delivery. The authors of this study evaluated mesotherapy of dutasteride solution to the scalp used in combination with oral minoxidil compared with oral minoxidil alone.

While blinded investigators identified significant improvements of hair growth for the combination treatment compared with oral minoxidil alone at the vertex scalp, the patients were remarkably satisfied in both groups, with no statistically significant difference. The limitation of the study included lack of treatment blinding and retrospective data analysis. I would like to see the use of placebo injections to evaluate the possible role that the injections themselves had on hair growth, as can be seen with microneedling.

While the study suggests that there may be benefits of dutasteride mesotherapy at the vertex scalp when used along with oral minoxidil, one must consider that there is a significant added cost for this in-office procedure. Given that patients were equally satisfied with the use of single-agent low-dose oral minoxidil, I don't necessarily see a big need for the addition of the mesotherapy. Of note, the dutasteride 0.01% solution that was used for mesotherapy treatment in this study is not currently available in the US.

Abstract

Oral dutasteride (OD) is an effective treatment for androgenetic alopecia (AGA); many men are reluctant to treat their AGA with systemic 5α-reductase enzyme inhibitors due to risk of adverse sexual side-effects. Dutasteride intralesional injections may be a useful antiandrogens alternative therapy for AGA; however, information of its effectiveness is scarce. Our objective was to investigate the effectiveness and safety of the dutasteride intralesional microinjections (DIM) with oral minoxidil (OM) compared with OM monotherapy in men with AGA.

Journal of the European Academy of Dermatology and Venereology: JEADV

Dutasteride intralesional microinjections in combination with oral minoxidil vs. oral minoxidil monotherapy in men with androgenetic alopecia: a retrospective analysis of 105 patients

J Eur Acad Dermatol Venereol 2022 Mar 12;[EPub Ahead of Print], CD Villarreal-Villarreal, E Boland-Rodriguez, S Rodríguez-León, F Le Voti, S Vano-Galvan, RD Sinclair

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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LON late onset neutropenia from rituximab...

EARLY RECOGNITION OF RITUXIMAB-INDUCED LATE ONSET NEUTROPENIA IS ESSENTIAL

By Warren R. Heymann, MD, FAAD
April 13, 2022
Vol. 4, No. 15

Rituximab is an anti-CD20 chimeric antibody directed against a surface transmembrane protein marker (CD20) expressed on B-cells during differentiation from pre B-cell until the plasma cell stage, involved in the maturation and activation of B cells. Approved in 1998, rituximab's off-label use has been expanding beyond its other FDA-approved indications (CD-20 positive B-cell non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, microscopic polyangiitis, and granulomatosis with polyangiitis). The list of off-label uses of rituximab continues to increase exponentially; from a dermatological perspective, its use in bullous pemphigoid, dermatomyositis, systemic lupus erythematosus, and refractory graft-versus-host disease are just a few examples where the drug may be impactful. (1)

Rituximab's well-recognized adverse events include infusion reactions, lymphopenia, hepatitis B virus reactivation, and progressive multifocal leukoencephalopathy. (2) Early-onset neutropenia is extremely rare, with only a handful of cases reported to date. (3) Rituximab-induced late-onset neutropenia (R-LON), although underrecognized, has been increasingly reported. According to the National Cancer Institute common toxicity criteria, R-LON is defined as unexplained grade 3 or more neutropenia (<1.0×103/μL) occurring at least 3–4 weeks after the rituximab infusion. (4) Other authors define R-LON as (<1.5×103/μL) after at least 4 weeks — the end point is not well-defined, being reported as late as 2 years following treatment.

Increasingly, extended courses of rituximab are being utilized to keep patients in remission. Rashid et al have demonstrated how maintenance infusions have prevented relapses of pemphigus. (5) According to Hosp et al, "LON is not infrequent. Its incidence is estimated at approximately 6.0% but might vary within a broad range (1.3% –29.9%). The risk of LON possibly depends on the underlying disease, and is supposed to be highest in coexisting lupus erythematosus. Comedication with disease-modifying antirheumatic drugs does not seem to influence its incidence." (6) Zonozi et al identified 107 episodes of LON in 71 patients. The cumulative incidence at 1 year was 6.6% (the incidence rate in the first year was higher compared to thereafter). Systemic lupus erythematosus and combination therapy with cyclophosphamide were each independently associated with an increased risk of LON. (7)

Illustration for DWII on early recognition of Rituximab-induced late onset neutropenia

JAAD 2005; 52: 839-845.

Is R-LON clinically significant? In their review, Hosp et al observed that although patients are frequently asymptomatic, severe infectious complications, including fatalities, have occurred. Administration of filgastrim (G-CSF) has been demonstrated to shorten time to recovery but did not affect overall outcomes. (6) Zonozi et al reported that fever and sepsis complicated 31.3% and 8.5% of episodes, respectively. Most patients (69%) were treated with filgrastim. Rituximab rechallenge occurred in 87% of patients, of whom 21% developed recurrent LON. (7) Boch et al identified LON in 5 of 117 rituximab-treated pemphigus patients compared to none of 15 patients who did not receive the drug. The R-LON in their patients was short-lived; none required specific therapy (antibiotics, filgastrim) or hospitalization. (8)

The pathomechanism(s) of R-LON remain to be determined. Hypotheses include the production of antineutrophil antibodies, expansion of large granular lymphocyte cells and aberrant B-cell reconstitution, and the association of an FcgRIIIa polymorphism. (2) Immunodysregulation during B-cell recovery coinciding with excess levels of B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) may be at play. (6) The presumption is that B-cell depletion leads to alterations in hematopoietic growth factors that promote lymphopoiesis and downregulate granulopoiesis. (7)

More will be learned about R-LON with increasing experience and study. Dermatologists must be aware of this adverse reaction of rituximab and monitor patients accordingly. While most patients will be fine, that is not a guarantee, and vigilance in recognizing severe infection is mandatory. As the sage Yogi Berra eloquently stated: "It gets late early out there."

Point to Remember: Late-onset neutropenia has been increasingly recognized in patients receiving rituximab. Although usually short-lived and without clinical consequence, severe infections and fatalities have been reported. Dermatologists need to be cognizant of this adverse reaction and monitor patients carefully during their course of rituximab therapy.

Our expert's viewpoint

Robert A. Somer, MD
Professor of Medicine, Cooper Medical School of Rowan University
Head, Division of Hematology and Medical Oncology; Executive Director, Clinical Trials Program
MD Anderson Cancer Center at Cooper

Dermatologists must be aware of the risks of rituximab, as use of this agent increases, not only for the treatment of pemphigus vulgaris, but other dermatologic conditions as mentioned above. As use of rituximab expands to treat multiple autoimmune disorders, sub-specialists will need to remain cognizant of the risks and benefits of this agent and monitor CBCs not only during the course of treatment but also thereafter. LON is much more common than we initially thought, and often found incidentally. Patients with pemphigus vulgaris may be at higher risk of cellulitis compared to other indications, if they experience rituximab associated LON. Luckily, most cases reverse and are unlikely to require therapy. If severe infections or sepsis do exist, treatment with G-CSF may be necessary. As more dermatologists get comfortable prescribing this agent for infusion, they must remain vigilant in monitoring. More investigation is certainly needed to accurately define the mechanism of LON which can then lead to prevention and treatment strategies as rituximab use continues to increase.

Hanif N, Anwer F. Rituximab. 2020 Nov 3. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–.
Sahu KK, Petrou N, Cohn Z, Khanna S. Rituximab-induced late-onset neutropenia. BMJ Case Rep. 2019 Dec 29;12(12):e233569.
Shah S, Kavadichanda CG, Belani P, Ganesh RN, Negi VS. Early onset neutropenia and thrombocytopenia following rituximab in lupus nephritis. Int J Rheum Dis. 2019 May;22(5):946-950.
Sahu KK, Petrou N, Cohn Z, Khanna S. Rituximab-induced late-onset neutropenia. BMJ Case Rep. 2019 Dec 29;12(12):e233569.
Rashid H, Lamberts A, van Maanen D, Bolling MC, Diercks GFH, Pas HH, Jonkman MF, Horváth B. The effectiveness of rituximab in pemphigus and the benefit of additional maintenance infusions: Daily practice data from a retrospective study. J Am Acad Dermatol. 2020 Nov;83(5):1503-1505.
Hosp C, Goebeler M, Benoit S, Stoevesandt J. Rituximab-mediated late onset neutropenia in autoimmune blistering diseases: negligible or under-estimated threat? J Dtsch Dermatol Ges. 2020 Oct;18(10):1162-1164.
Zonozi R, Wallace ZS, Laliberte K, Huizenga NR, Rosenthal JM, Rhee EP, Cortazar FB, Niles JL. Incidence, Clinical Features, and Outcomes of Late-onset Neutropenia from Rituximab for Autoimmune Disease. Arthritis Rheumatol. 2020 Sep 6. doi: 10.1002/art.41501. Epub ahead of print. PMID: 32892495.
Boch K, Zillikens D, Langan EA, Schmidt E, Ludwig RJ. Low prevalence of late-onset neutropenia after rituximab treatment in patients with pemphigus. J Am Acad Dermatol. 2020 Dec;83(6):1824-1825.

All content found on Dermatology World Insights and Inquiries, including: text, images, video, audio, or other formats, were created for informational purposes only. The content represents the opinions of the authors and should not be interpreted as the official AAD position on any topic addressed. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment.

Dermatología en Costa Rica

Saturday, April 30, 2022

Published in Dermatology News · April 29, 2022 Annual Costs Estimated for Wart Treatment in the U.S. for 2015-2017

Annual Health Care Utilization and Costs for Treatment of Cutaneous and Anogenital Warts Among a Commercially Insured Population in the US, 2017-2019

Thursday, April 28, 2022

Oximetazolina para ptosis palpebral

EYE-OPENING NEWS ABOUT OXYMETAZOLINE

Acknowledgement: I thank Lacy L. Sommer, MD, FAAD, for her photographic skills.

Warren R. Heymann, MD, FAAD

Practice manager

Our expert's viewpoint

Monday, April 25, 2022

Journal Scan / Research · April 20, 2022 Leukocyte Adhesion and Rolling in Skin With Patient Outcomes After Hematopoietic Cell Transplantation Using Noninvasive Reflectance Confocal Videomicroscopy JAMA Dermatology

TAKE-HOME MESSAGE

IMPORTANCE

OBJECTIVE

DESIGN, SETTING, AND PARTICIPANTS

MAIN OUTCOMES AND MEASURES

RESULTS

CONCLUSIONS AND RELEVANCE

Association of Leukocyte Adhesion and Rolling in Skin With Patient Outcomes After Hematopoietic Cell Transplantation Using Noninvasive Reflectance Confocal Videomicroscopy

Journal Scan / Research · April 22, 2022 Disproportional Signal of Sexual Dysfunction Associated With Finasteride Use in Young Men With Androgenetic Alopecia Journal of the American Academy of Dermatology

TAKE-HOME MESSAGE

Disproportional signal of sexual dysfunction reports associated with finasteride use in young men with androgenetic alopecia: A pharmacovigilance analysis of VigiBase

Wednesday, April 20, 2022

ONE TOKER OVER THE LINE: CLARIFYING TOKER CELL HYPERPLASIA IN ZUSKA DISEASE AND ITS RELATIONSHIP TO HIDRADENITIS SUPPURATIVA

Our expert's viewpoint

DW Insights and Inquiries archive

Saturday, April 16, 2022

Autoinoculation vs 35% Trichloroacetic Acid for Molluscum Contagiosum Journal of the American Academy of Dermatology

TAKE-HOME MESSAGE

A randomized controlled pilot study of autoinoculation versus 35% trichloroacetic acid for the treatment of molluscum contagiosum

Dutasteride Intralesional Microinjections in Combination With Oral Minoxidil vs Oral Minoxidil Monotherapy in Men With Androgenetic Alopecia Journal of the European Academy of Dermatology and Venereology: JEADV

TAKE-HOME MESSAGE

Dutasteride intralesional microinjections in combination with oral minoxidil vs. oral minoxidil monotherapy in men with androgenetic alopecia: a retrospective analysis of 105 patients

Wednesday, April 13, 2022

LON late onset neutropenia from rituximab...

EARLY RECOGNITION OF RITUXIMAB-INDUCED LATE ONSET NEUTROPENIA IS ESSENTIAL

Our expert's viewpoint

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