Evaluation of Malignancy Risk in Scleroderma by Antibody Profile The British Journal of Dermatology

TAKE-HOME MESSAGE

• In this retrospective chart analysis spanning from 2000 to 2017, the authors identified 125 systemic sclerosis patients, including 59 (47.2%) with a cancer diagnosis. Breast (n=15), genitourinary (n=11), and lung (n=10) were the most commonly observed malignancies. The incidence of malignancy was higher in patients with anti-RNAP III antibodies, particularly within 3 years of systemic sclerosis diagnosis.

• This study demonstrated a higher prevalence of malignancy in patients with systemic sclerosis than has been previously reported, which may be related to an older study population, higher incidence of anti-RNAP III, and/or greater disease severity seen in their tertiary care center. Regardless, authors conclude that dermatologists should consider malignancy screening in patients with systemic sclerosis within 3 years of onset.

– Caroline K. Crabtree, MD

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Skin Care Physicians of Costa Rica

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Published in Dermatology

Journal Scan / Research · September 01, 2020

Association Between Halo Nevi and Melanoma in Adults

Journal of the American Academy of Dermatology

TAKE-HOME MESSAGE

• In this retrospective review, the charts of adult patients with a new diagnosis of halo nevi (HN) were reviewed to determine the rate of melanoma development within 1 year of when the HN diagnosis was made. In the 879 patient charts reviewed, 95 melanomas were found. Only 9 occurred within 1 year of HN development, which yielded a melanoma incidence rate in patients with HN diagnosis of 0.01 per person per year. The remaining 86 melanomas occurred either before the HN diagnosis or after a 1-year period. This study suggests that, in an adult who develops new-onset HN, the risk of developing a cutaneous melanoma is as low as 1% per person per year. This risk is similar to that incurred by having multiple atypical nevi or a personal or family history of melanoma.

• The authors conclude that an annual skin cancer screening examination is adequate for screening for melanoma in these patients with new-onset HN.

– Margaret Hammond, MD

Written by

 

 

Christine Jaworsky MD

This pivotal study is a significant multicenter, retrospective chart analysis of clinical and histologic records at eight university hospitals. The authors identified 879 adults over the age of 18 with a total of 888 halo nevi diagnoses. Patients who were treated for melanoma with immunotherapy were excluded. There were 95 occurrences of melanoma in the study population. In 78 patients, melanoma preceded a halo nevus. In 9 patients, halo nevi were diagnosed up to 1 year prior the diagnosis of melanoma. In 8 patients, a primary cutaneous melanoma occurred more than 1 year after a halo nevus was detected. All the melanomas diagnosed were primary cutaneous melanomas; none were primary extracutaneous melanoma, metastatic melanoma, or synchronous melanoma in a halo nevus. All the halo nevi were single, not multiple, in patients identified with melanoma.

The literature to date advocates for extensive melanoma screening for primary and visceral melanomas in adults with a halo nevus despite evidence supporting an association between halo nevi and melanoma. The authors' finding of a 1% risk of developing a primary cutaneous melanoma in the year following a halo nevus indicates that there is no need for an exhaustive cutaneous and systemic workup in adult patients with a new-onset halo nevus. The risk of developing a melanoma in adult patients with a halo nevus is similar to that of patients with atypical nevi or a personal/family history of melanoma. The authors state that a history of vitiligo and a halo nevus is not significantly associated with risk of melanoma. It would be interesting to see if the same holds true in the less common patients with multiple halo nevi.

Abstract

The halo nevus (HN) is thought to be of little concern in children. In adults, however, a new-onset HN has been suggested to be a harbinger of melanoma – either within the HN or at distant cutaneous or non-cutaneous sites – based on case reports and small case series.1,2 Multiple widely-used dermatologic reference texts3,4 and online references (such as UpToDate.com, DermNetNZ.org) advocate for extensive melanoma screening in adults with new-onset HN, including full cutaneous, oral, ophthalmic, and vaginal examinations, despite limited evidence supporting an association between HN and melanoma. We aimed to further investigate the association between new-onset HN and melanoma in adults by evaluating the incidence of melanoma in the year following a new HN diagnosis.

Journal of the American Academy of Dermatology

Association Between Halo Nevi and Melanoma in Adults: A Multi-Center Retrospective Case Series

J Am Acad Dermatol 2020 Aug 18;[EPub Ahead of Print], D Haynes, JL Strunck, J Said, I Tam, A Varedi, CA Topham, B Olamiju, BM Wei, MK Erickson, LL Wang, A Tan, R Stoner, RI Hartman, E Lilly, D Grossman, JA Curtis, JS Westerdahl, JS Leventhal, JN Choi, EY Chu, ME Ming, JA Stein, TN Liebman, E Berry, TM Greiling 

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Skin Care Physicians of Costa Rica

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Lupus inducido por farmacos

Original Investigation 

September 2, 2020

Association Between Drug Use and Subsequent Diagnosis of Lupus Erythematosus

Jeanette Halskou Haugaard, MD¹; Kristian Kofoed, MD, PhD¹; Gunnar Gislason, MD, PhD²; et alLene Dreyer, MD, PhD^3,4; Alexander Egeberg, MD, PhD¹

Author Affiliations

JAMA Dermatol. Published online September 2, 2020. doi:10.1001/jamadermatol.2020.2786

Key Points

Question  What is the association between drug use and a subsequent diagnosis of cutaneous lupus erythematosus or systemic lupus erythematosus?

Findings  In this nationwide case-control study, many significant associations were found between the use of a variety of drugs and a subsequent diagnosis of cutaneous lupus erythematosus or systemic lupus erythematosus. Relatively well-established causal associations together with some new plausible causal associations were observed.

Meaning  The findings indicate that physicians must be aware that a newly diagnosed case of cutaneous lupus erythematosus or systemic lupus erythematosus could be drug induced.

Abstract

Importance  It has been estimated that up to 30% of all subacute cutaneous lupus erythematosus (CLE) cases and up to 15% of systemic lupus erythematosus (SLE) cases are drug induced. Based on numerous case reports and several epidemiologic studies, more than 100 drugs from more than 10 drug classes are suspected to cause drug-induced lupus erythematosus.

Objective  To examine the association between drug use and a subsequent diagnosis of CLE or SLE based on a systematic screening process of the drugs in the Anatomical Therapeutic Chemical classification system in a nationwide setting.

Design, Setting, and Participants  A matched case-control study was conducted using all incident cases of CLE and SLE registered in the Danish National Patient Register between January 1, 2000, and December 31, 2017. Patients with CLE and patients with SLE were matched (1:10) on age and sex, with individuals from the general population serving as controls.

Exposures  To select which drugs to examine for an association with CLE or SLE, a screening process of all drugs was performed, including drugs filled at pharmacies and drugs administered in hospitals.

Main Outcomes and Measures  Odds ratios (ORs) were calculated for the association between exposures to certain drugs and the subsequent diagnosis of CLE or SLE.

Results  In all, 3148 patients with CLE (n = 1298; 1022 women [78.7%]; median age at diagnosis, 50.5 years [interquartile range, 39.4-62.2 years]) or SLE (n = 1850; 1537 women [83.1%]; median age at diagnosis, 45.0 years [interquartile range, 33.6-56.4 years]) and 31 480 controls (25 590 women [81.3%]; median age, 47.5 years [interquartile range, 35.9-59.5 years]) were found. Many significant associations between drug use and a subsequent diagnosis of CLE and SLE were observed. Many associations were likely due to protopathic bias. However, new plausible causal associations were observed between CLE or SLE and some drugs, including fexofenadine hydrochloride (SLE: OR, 2.61 [95% CI, 1.80-3.80]; CLE: OR, 5.05 [95% CI, 3.51-7.26]), levothyroxine sodium (SLE: OR, 2.46 [95% CI, 1.97-3.07]; CLE: OR, 1.30 [95% CI, 0.96-1.75]), metoclopramide hydrochloride (SLE: OR, 3.38 [95% CI, 2.47-4.64]; CLE: OR, 1.47 [95% CI, 0.85-2.54]), and metronidazole hydrochloride (SLE: OR, 1.57 [95% CI, 1.09-2.27]; CLE: OR, 1.93 [95% CI, 1.25-2.97]).

Conclusions and Relevance  The study's findings suggest that physicians should be cognizant about whether a new case of CLE or SLE could be drug induced. Furthermore, the results highlight that the reported associations in the published literature may be due to publication or protopathic bias.

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Skin Care Physicians of Costa Rica

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Interesante: Infliximab en HS, Lido buferizada, meds en psor y lavado de manos...

What's hot

September 1, 2020

In this monthly column, members of Dermatology World's Editorial Advisory Workgroup identify exciting news from across the specialty.  

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HARRY DAO JR., MD

Hidradenitis suppurativa (HS) ranks high on my list of tough conditions to manage. In 2015, adalimumab's new status as the sole FDA-approved biologic for HS gave me high hopes. These hopes were dashed as I accumulated patients who flared despite use of the drug, and I would often turn to infliximab out of desperation. Optimal infliximab dosing remained elusive, yet the always-pervasive fear of prescribing high doses for extended amounts of time was paralyzing. As such, I was glad to see a prospective analysis based out of Albert Einstein (doi:10.1016/j.jaad.2019.09.071).

In this study, two sets of patients were enrolled from March 2018 to February 2019. Most patients per treatment algorithm were treated concurrently with topical antibiotics, oral antibiotics, and anti-androgen therapy. The first cohort consisted of infliximab naïve patients (n=42), who received an induction dose of 7.5mg/kg at weeks 0, 2, and 6, followed by a maintenance dose of 7.5 mg/kg every four weeks. The second cohort consisted of patients who failed infliximab 7.5 mg/kg dosing prior to study inclusion (n=14), as well as those escalated from the infliximab 7.5 mg/kg cohort due to insufficient disease control (n=2). This group escalated to infliximab 10mg/kg every four weeks.

In the infliximab 7.5 mg/kg group, clinical response was seen in 20/42 (47.6%) at week four and 17/24 (70.8%) at week 12. Two-thirds of patients had complete resolution of pain within four weeks of treatment initiation. Dose escalation to infliximab 10 mg/kg allowed even more patients to improve: 6/16 (37.5%) and 6/12 (50%) patients achieved clinical response at four and 12 weeks, respectively.

Infliximab via this high-dose, high-frequency regimen, initiated at 7.5 mg/kg every four weeks with optional dose escalation to 10 mg/kg every four weeks, in the setting of inadequate disease control, can be a very helpful tool to reduce HS disease activity and pain.

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SETH MATARASSO, MD

1% lidocaine is often the anesthetic of choice to reduce pain for many procedures, but the concentration can range between 0.5% to 2.5%. Lidocaine can be used alone. However, the addition of epinephrine at 1:100,000 can be pre-mixed for its vasoconstrictive properties. Lidocaine has an acidic pH of 2.5-4.0 and the detection of acid-sensing ion channel receptors is responsible for the burning sensation during infiltration. Pain can be reduced when lidocaine (with or without epinephrine) is buffered to a neutral more physiologic solution by the addition of 8.4% sodium bicarbonate (sodium hydrogen carbonate). The consequent decreased lidocaine concentration and alteration in pH does not interfere or shorten the local anesthetic effect (numbness).

A recent double-blinded study reported that the optimal quantification of the amount of buffered solution that was required was a 3:1 ratio; 3 ml of lidocaine with epinephrine added to 1 ml of sodium bicarbonate. It was less painful during infiltration than both a 9:1 ratio as well as a placebo (0.9% sodium chloride pH 6.3). The stability and shelf life of neutralized lidocaine is limited, making storage of the compounded product a limiting factor. There are no published guidelines that document duration of compounded anesthesia and in the present trial, the authors interval between mixing the anesthetic with the sodium bicarbonate and administering the solution to one minute so that degradation would not be a factor. The authors warn that there are no rules to simplify compounding to ensure product quality and that the results of their trial cannot be extrapolated to other local anesthetics (J Am Acad Derm. 2020; 83:159-65).

There is an adage that says that "it costs seven times more to attract a new patient than to retain one." As a corollary, it can also be stated that "if you pain them, you do not retain them."

Editor's note: Effective Dec. 2016, the FDA prohibits office-use compounding, which is when traditional compounding pharmacies provide compounded medications as office stock without a patient-specific prescription. Find out whether the type of compounding you are prescribing or performing is compliant with FDA regulations.

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SYLVIA HSU, MD

Psoriasis treatments trend toward the use of biologics. Data from the 2001-2015 National Ambulatory Medical Care Survey — a representative sample of U.S. office-based physician visits — showed that biologic use for psoriasis increased from the 2001-2005 period to the 2011-2015 period, especially among dermatologists (from 4.1% to 12.0%), commercially insured patients (from 4.8% to 17.3%), patients in metropolitan areas (from 4.1% to 12.0% ), and patients with psoriatic arthritis (from 19.1% to 27.6%) (J Am Acad Derm. 2020; 83(1): 256-257). Acitretin prescriptions decreased over time (from 4.5% to 1.7%), and oral immunosuppressants and phototherapy use stayed about the same. Biologics were used at much higher rates (more than double) than oral medications and phototherapy combined. However, increasing biologic use was not offset by decreases of other treatment options.

A disturbing finding from this study was that systemic steroid use in psoriasis patients increased in metropolitan areas from 2001-2005 to 2011-2015 (from 1.7% to 5.6%). Systemic steroids are not recommended in U.S. or European psoriasis treatment guidelines, because of adverse events, such as rebound flares, erythroderma, and generalized pustular psoriasis. The increased use of systemic steroids over time in the management of psoriasis is quite concerning and is a practice trend that needs to be addressed and reversed.

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CRISTEN MOWAD, MD

A recent article in Dermatitis highlights hand hygiene challenges, particularly in the hospital setting, given the ever-present possible exposure to COVID-19 patients and the risk of in-hospital transmission (doi: 10.1097/DER.0000000000000639). Washing with soap and water and using alcohol-based rubs can help to fight against transmission. The authors also comment on the risk factors associated with hand dermatitis due to the heightened need and increased frequency of hand hygiene: atopic dermatitis, male gender, long work hours, and younger age as factors that are increasingly associated with hand dermatitis.

Reviewing certain hand hygiene practices, the authors comment that alcohol-based hand rubs increase compliance as they can be more widely distributed where a sink and soap are not present and may be better tolerated. Alcohol-based hand rubs are well tolerated but can result in irritant contact dermatitis, especially in those with pre-existing skin disease. Emollients can be used to mitigate these effects. Chlorhexidine, according to the authors, appears to have lower efficacy against SARS-CoV-2 compared to 70% ethanol, hydrogen peroxide 0.5%, or sodium hypochorite 0.1%. In addition to irritant contact dermatitis, allergic contact dermatitis is also seen with chlorhedixine.

Regular use of soap and water is effective and with increased frequency often results in skin irritation presenting as rough, dry, sometimes fissured skin that has erythema and pruritus as features. Self-reports of hand dermatitis increase with increased frequency of hand washing with soap and water. Educating patients on early treatment and increased use of hand creams can be helpful.

The authors comment that health care worker compliance with hand hygiene may be impacted by hand dermatitis. Use of alcohol-based hand rubs may prove less irritating than use of soap and water and result in better compliance. Hand hygiene is critical to preventing the further spread of SARS-CoV-2. Educating health care workers, and our patients, regarding prevention of hand dermatitis, completely rinsing soap and water, drying the hands, and recognizing hand dermatitis early in order to intervene with increased use of emollients is important to help reduce hand dermatitis. 

Melanosis Vulvar, lesion de aspecto aparatoso, pero de bajo riesgo.

Clinical and Dermoscopic Features of Vulvar Melanosis

JAMA Dermatology

TAKE-HOME MESSAGE

• In this observational cohort study in Italy spanning from 1998 to 2019, 129 women with vulvar melanosis were followed for a median of 13 years. Most women were premenopausal; the most common location for vulvar melanosis was the labia minora (43%); and 70% of lesions were smaller than 1 centimeter. Although nearly one-third of patients had slow evolution of the lesion, this ultimately stabilized, and no malignancy was noted in any of the patients' lesions during the follow-up period. In all 47 patients (36%) who underwent biopsy, vulvar melanosis was the final diagnosis. The most common dermoscopic pattern observed (75%) was homogenous or non-homogenous diffuse pigmentation in various shades of brown (100%) or black (60%), with only the rare presence of other colors and absence of other distinguishing features.

• Slow enlargement and change in brown–black pigment was not associated with malignant evolution of vulvar melanosis in this cohort.

– Caroline K. Crabtree, MD

Written by

Kelly H. Tyler MD, FACOG, FAAD

Benign vulvar melanosis can appear alarming on clinical exam because it is often darkly pigmented or even black, and many patients are unaware of its presence and cannot provide history regarding change or stability. The authors performed an excellent study outlining the key dermoscopic features of vulvar melanosis, especially with regard to features which differentiate it from vulvar melanoma.

The authors found that, if on dermoscopy a pigmented vulvar lesion is either a homogenous or non-homogenous black or brown color, lacks red, gray, or blue colors, and/or lacks typical dermoscopic parameters for melanocytic lesions (pigment network, dots and globules, pseudopods, and streaks), the clinician can diagnose vulvar melanosis with confidence and avoid biopsy. Most importantly, none of their patients with vulvar melanosis developed melanoma during the 20-year follow-up period, indicating that vulvar melanosis is indeed a benign entity with an extremely low risk of malignant transformation.

Although a small number of patients with vulvar melanosis in this study eventually developed an inflammatory vulvar dermatosis (such as lichen sclerosus), I personally see a large number of patients with either active or previously active inflammatory vulvar diseases who have vulvar melanosis; so, perhaps future studies are warranted to confirm this association.

Abstract

Importance

Vulvar melanosis is a common pigmentary change that accounts for most pigmented vulvar lesions. It presents as single or multiple asymptomatic macules or patches of varying size and color that may be asymmetric with poorly defined borders. The differential diagnosis of melanocytic lesions includes melanoma, which creates anxiety for patients and the physicians who diagnose the condition and treat the patients.

Objective

To evaluate the clinical and dermoscopic features of vulvar melanosis and their changes over time.

Design, Setting, and Participants

In this cohort study, patients with vulvar melanosis were recruited and followed up in the Department of Dermatology, University of Florence, Florence, Italy, between January 1, 1998, and June 30, 2019. Data on patient characteristics and on both the clinical and dermoscopic features of the vulvar lesions were collected. Each lesion was photographed clinically and dermoscopically at initial evaluation and at annual follow-up visits.

Main Outcomes and Measures

The clinical, dermoscopic, and histopathologic features of vulvar melanosis and their changes over time.

Results

This cohort study included 129 women (mean age at diagnosis, 46 years [range, 19-83 years]) with vulvar melanosis. A total of 87 patients (67%) with vulvar melanotic lesions were premenopausal, and 84 patients (65%) had received some type of hormone therapy. The most frequent location for vulvar melanosis was the labia minora (55 [43%]), followed by the labia majora (33 [26%]). In 39 of 129 cases (30%), the lesions increased in size and changed color after initial evaluation but ultimately stabilized. No malignant evolution was documented in any patient during a median follow-up of 13 years (range, 5-20 years).

Conclusions and Relevance

This study suggests that vulvar melanosis was a benign entity, and changes in lesions over time did not signify malignant transformation. An association between hormonal status and vulvar melanosis may be hypothesized.

JAMA Dermatology

Clinical and Dermoscopic Features of Vulvar Melanosis Over the Last 20 Years

JAMA Dermatol 2020 Aug 12;[EPub Ahead of Print], V De Giorgi, A Gori, L Salvati, F Scarfì, P Maida, L Trane, F Silvestri, F Portelli, F Venturi, P Covarelli, D Massi

Melanoma en adultos con Nevus de Sutton menor al 1% por persona por año... bajo pero tomar en cuenta.

September 01, 2020

Association Between Halo Nevi and Melanoma in Adults

Journal of the American Academy of Dermatology

TAKE-HOME MESSAGE

• In this retrospective review, the charts of adult patients with a new diagnosis of halo nevi (HN) were reviewed to determine the rate of melanoma development within 1 year of when the HN diagnosis was made. In the 879 patient charts reviewed, 95 melanomas were found. Only 9 occurred within 1 year of HN development, which yielded a melanoma incidence rate in patients with HN diagnosis of 0.01 per person per year. The remaining 86 melanomas occurred either before the HN diagnosis or after a 1-year period. This study suggests that in an adult who develops new-onset HN, the risk of developing a cutaneous melanoma is as low as 1% per person per year. This risk is similar to that incurred by having multiple atypical nevi or a personal or family history of melanoma.

• The authors conclude that an annual skin cancer screening examination is adequate for screening for melanoma in these patients with new-onset HN.

– Margaret Hammond, MD

Abstract

The halo nevus (HN) is thought to be of little concern in children. In adults, however, a new-onset HN has been suggested to be a harbinger of melanoma – either within the HN or at distant cutaneous or non-cutaneous sites – based on case reports and small case series.^1,2 Multiple widely-used dermatologic reference texts^3,4 and online references (such as UpToDate.com, DermNetNZ.org) advocate for extensive melanoma screening in adults with new-onset HN, including full cutaneous, oral, ophthalmic, and vaginal examinations, despite limited evidence supporting an association between HN and melanoma. We aimed to further investigate the association between new-onset HN and melanoma in adults by evaluating the incidence of melanoma in the year following a new HN diagnosis.

Journal of the American Academy of Dermatology

Association Between Halo Nevi and Melanoma in Adults: A Multi-Center Retrospective Case Series

J Am Acad Dermatol 2020 Aug 18;[EPub Ahead of Print], D Haynes, JL Strunck, J Said, I Tam, A Varedi, CA Topham, B Olamiju, BM Wei, MK Erickson, LL Wang, A Tan, R Stoner, RI Hartman, E Lilly, D Grossman, JA Curtis, JS Westerdahl, JS Leventhal, JN Choi, EY Chu, ME Ming, JA Stein, TN Liebman, E Berry, TM Greiling

Miel, para preservar muestras para inmunofluoresencia...en vez de Solución de Michel.

Dermatopathology's taste of honey

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By Warren R. Heymann, MD
September 2, 2020
Vol. 2, No. 34

Recently, on our consult service, my resident and I were assessing a patient with a potential autoimmune bullous disease; we concurred that a skin biopsy for routine microscopy and direct immunofluorescence (DIF) was warranted. "I'll have to come back tomorrow," my resident proclaimed. "I don't have the DIF transport medium with me!" (Michel's medium — MM — contains ammonium sulfate, N-ethylmalmeimide, potassium citrate buffer, magnesium sulfate, and distilled water.) I didn't argue. It was not an emergency, and besides, were there any other options?

Apparently, the answer is a resounding "yes!"

Despite the use of serological ELISA tests utilized for diagnosing autoimmune bullous disorders, DIF of perilesional skin remains the diagnostic gold standard, with sensitivities ranging from 82-91% and specificity of 98%. (1) For transport, saline-soaked gauze may be utilized, but the specimen must be delivered to the laboratory within 48 hours. Given the vagaries of specimen pick-up schedules in my practice, I am not comfortable with that time frame. (2)

The answer for this dilemma is sweet — as in honey. Honey has been utilized since antiquity as a binder vehicle, but also topically for medicinal and cosmetic purposes. Ancient Greeks and Egyptians used honey to treat skin wounds, burns, and infections. Persian traditional medicine documented the efficacy of honey for the treatment of eczema. It has also been utilized for tinea, seborrhea, dandruff, diaper dermatitis, psoriasis, hemorrhoids, and anal fissures. Honey is a bee‐derived, supersaturated solution composed mainly of fructose and glucose, and containing proteins and amino acids, vitamins, enzymes, minerals, and other minor components. Mechanisms of action include antioxidant activity, the induction of cytokines and matrix metalloproteinase expression, as well as epithelial‐mesenchymal transition in wounded epidermis. (3,4)

JAAD Case Rep 2016; 2 (4): 326-328.

Rao et al, based on the centuries-old use of honey as a preservative, evaluated the use of honey as transport medium for DIF. A total of 36 snap‐frozen DIF-positive biopsy samples were divided into 3 groups of 12 specimens each. The biopsy specimens were placed in contact lens holding boxes and approximately 3 ml of honey was poured on top of the specimens. These samples were processed at the end of days 5, 10, and 20, respectively. The DIF was positive in all except for one case of dermatitis herpetiformis (DH) in the study. Limitations of this study were that fresh biopsy samples were not utilized and the efficacy of honey as DIF transport medium was not directly compared to MM. (5)

Kumudhini et al compared honey to MM as a transport medium for skin biopsy specimens used for DIF and antigen mapping. Group I consisted of 45 freshly‐taken skin specimens earmarked for DIF testing. It was divided into three groups (A, B, and C), each containing 15 specimens. Biopsy specimens were sliced into two, one each for MM and honey. Samples in group A were processed at the end of week 1 while those in group B and C were processed at the end of weeks 2 and 4, respectively. Group II consisted of five specimens of epidermolysis bullosa (EB) which was further divided into three groups; two specimens were processed for antigen mapping at the end of week 1, while others were processed at the end of week 2 (two specimens) and 4 (one specimen). Sensitivity of honey as a transport medium for skin biopsy specimens was 100%, 92.6%, and 53.8% at weeks 1, 2, and 4, respectively. The antigen mapping was positive in all specimens. The authors concluded that the utility of honey was comparable to MM for DIF samples tested at weeks 1 and 2 but was lower at week 4. If the samples transported in honey can reach the DIF laboratory within 2 weeks, the immunoreactants will be well-preserved for identification. (6)

In conclusion, if you run out of MM for your DIF specimens, go to the local market, grab some honey as transport medium, and send your specimen to the lab so it is received within two weeks. The only wrinkle in this otherwise sweet scenario is that there is a declining bumblebee population over the past decade attributable to habitat loss, changing climate, pathogen transmission, invasion of nonnative species, and pesticides. (7)

Point to Remember: Don't fret if you cannot find Michel's medium for your DIF specimen. A taste of honey will suffice!

Our expert's viewpoint

Kiran Motaparthi, MD

Preservation of immunoreactants for visualization during fluorescence microscopy requires flash or snap freezing. If freezing followed by cryosectioning is not possible directly after biopsy collection — a common scenario for dermatologists who are distant to a laboratory — a nonfixative transport medium should be used. (8) For up to 24 hours, normal saline is the optimal transport medium, given its low cost and higher specificity based on reduction of background fluorescence. Unfortunately, the sensitivity for immunoreactant detection decreases at 48 hours, limiting the use of saline in this context. (9) Specimens are technically viable in MM for up to 6 months (10), but for diagnostic utility, storage in MM for up to 2 weeks produces accurate immunofluorescence findings in 90% of cases. (11) As Dr. Heymann notes in his commentary, storage in honey for up to 2 weeks was recently found to deliver greater than 92% sensitivity for DIF, an impactful finding in settings where access to MM is limited by cost or availability. (12) In other words, if only 24 hours separates biopsy from freezing, normal saline is preferred. If transport requires between 1 and 14 days, either MM or honey should be used. Of these 3 media, honey is the most cost efficient, while MM is the most expensive. Importantly, if perilesional skin is inadvertently placed in formalin, the biopsy should be repeated. Autoantibodies cannot be detected in pemphigus and bullous pemphigoid after only 2 minutes and 10 minutes in formalin, respectively. (13)

Of interest to dermatopathologists who perform DIF, diagnostic immunofluorescence is consistently retained in frozen blocks for at least 4 months. (14) In DIF-positive slides stored at room temperature, a reliable diagnosis can still be made before 12 months. (15)

1. van Beek N, Zillikens D, Schmidt E. Diagnosis of autoimmune bullous disease. J Dtsch Dermatol Ges. 2018;16(9):1077-1091.

2. Elston DM, Stratman EJ, Miller SJ. Skin biopsy: Biopsy issues in specific diseases. J Am Acad Dermatol 2016; 74: 1-16.

3. McLoone P, Warnock M, Fyfe L. Honey: A realistic antimicrobial for disorders of the skin. J Microbiol Immunol Infect 2016; 49: 161-167.

4. Burlando B, Cornara L. Honey in dermatology and skin care: A review. J Cosmet Dermatol 2013; 12: 306-313.

5. Rao R, Jindal A, Bhogal B, Pai SB. Direct immunofluorescence microscopy of skin biopsy samples preserved in honey. J Am Acad Dermatol 2017; 76: 761-763.

6. Kumudhini S, Pai, Rao C, Rao R. A comparative study of Michel's medium versus honey as a transport medium versus honey as a transport medium for skin specimens prior to direct immunofluorescence microscopy and antigen mapping. J Cutan Pathol 2019; 46: 729-735.

7. Cameron SA, Sadd BM. Global trends in bumble bee health. Annu Rev Entomol 2019; Oct 14 [Epub ahead of print]

8. Patel AN, Simpson RC , Cohen SN. In a patient with an immunobullous disorder, is transportation of the skin biopsy in normal saline adequate for direct immunofluorescence analysis? A critically appraised topic. Br J Dermatol 2013;169:6-10.

9. Vodegel RM, de Jong MC, Meijer HJ, Weytingh MB, Pas HH , Jonkman MF. Enhanced diagnostic immunofluorescence using biopsies transported in saline. BMC Dermatol 2004;4:10.

10. Vaughan Jones SA, Salas J, McGrath JA, Palmer I, Bhogal GS , Black MM. A retrospective analysis of tissue-fixed immunoreactants from skin biopsies maintained in Michel's medium. Dermatology 1994;189 Suppl 1:131-2.

11. Nisengard RJ, Blaszczyk M, Chorzelski T , Beutner E. Immunofluorescence of biopsy specimens: comparison of methods of transportation. Arch Dermatol 1978;114:1329-32.

12. Kumudhini S, Pai S, Rao C , Rao R. A comparative study of Michel's medium versus honey as a transport medium for skin specimens prior to direct immunofluorescence microscopy and antigen mapping. J Cutan Pathol 2019;46:729-35.

13. Arbesman J, Grover R, Helm TN , Beutner EH. Can direct immunofluorescence testing still be accurate if performed on biopsy specimens after brief inadvertent immersion in formalin? J Am Acad Dermatol 2011;65:106-11.

14. Mackie RM, Young H , Campbell IA. Studies in cutaneous immunofluorescence. I. The effect of storage time on direct immunofluorescence of skin biopsies from bullous disease and lupus erythematosus. J Cutan Pathol 1980;7:236-43.

15. Dikicioglu E, Meteoglu I, Okyay P, Culhaci N , Kacar F. The reliability of long-term storage of direct immunofluorescent staining slides at room temperature. J Cutan Pathol 2003;30:430-6.

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