Hyperpigmented Macules and Patches on the Face: Exogenous Ochronosis or Lichen Planus Pigmentosus?

We present a case of a patient with a 10-year history of blue-black macules and patches on the face and an associated history of skin-lightening cream usage. The skin lightening cream contained hydroquinone, which is often associated with exogenous ochronosis (EO). Interestingly, the biopsy did not show characteristic findings of ochronosis, confusing the final diagnosis, however discontinuing the skin-lightening creams halted the progression of the patient's skin lesions supporting a diagnosis of EO. EO presents as asymptomatic hyperpigmentation after using products containing hydroquinone. This condition is most common in Black populations, likely due to the increased use of skin care products and bleaching cream containing hydroquinone in these populations. Topical hydroquinone is FDA-approved to treat melasma, chloasma, freckles, senile lentigines, and hyperpigmentation and is available by prescription only in the US and Canada. However, with the increased use of skin-lightening creams in certain populations, it is important for dermatologists to accurately recognize the clinical features of exogenous ochronosis to differentiate it from similar dermatoses. An earlier diagnosis can prevent the progression to severe presentations with papules and nodules. We summarize the clinical presentations diagnostic features, and treatment pearls, concluding with a discussion of the differential diagnoses.  J Drugs Dermatol. 2024;23(7):567-568.     doi:10.36849/JDD.8248.

Chrysiasis: Gold Aggregates Around a Nevus and Osteoma Cutis.

ABSTRACT: Parenteral gold has historically been used to treat several conditions, including rheumatoid arthritis. Gold administration leads to a variety of cutaneous reactions, including chrysiasis, which is a permanent blue-grey hyperpigmentation of the skin due to dermal gold deposition. In this report, we describe the case of a patient who received parenteral gold injections 22 years before the onset of her chrysiasis for the treatment of rheumatoid arthritis. Biopsy of the macules showed dermal gold deposits aggregating around a melanocytic nevus, as well as around preexisting osteoma cutis. To the authors' knowledge, this is the first report in the literature describing a case of chrysiasis with gold deposits concentrated around a melanocytic nevus and an area of osteoma cutis.

Calcium pantothenate is present in cosmetics and may cause allergic contact dermatitis.

Calcium pantothenate (CAS no. 137-08-6) is the calcium salt of pantothenic acid (vitamin B5). It is used in cosmetics due to its anti-static and hair conditioning properties. A 53-year-old female nurse's aide presented with intermittent facial eruptions (Figure S1). Patch tests were positive to calcium pantothenate, an ingredient of two of her products (a cleansing milk and a facial tonic). To our knowledge, no previous cases of sensitization from calcium pantothenate have been reported except for one case of systemic dermatitis from a nutritional supplement in a dexpanthenol-sensitized patient.

Facial contact dermatitis caused by cosmetic-relevant allergens.

BACKGROUND: Facial allergic contact dermatitis caused by cosmetic products is common. New allergens in cosmetics continuously emerge. OBJECTIVES: To investigate characteristics of patients with facial dermatitis (FD) between 2010 and 2019 including patch test results from cosmetic-related allergens and a new test series with cosmetic-relevant natural ingredients (CRNIs). METHODS: This is a retrospective study analysing demographics, clinical characteristics according to MOAHLFA index (male; occupation; atopic dermatitis; hand; leg; face; age ≥ 40 years), and patch test results to 27 cosmetic-relevant allergens in FD patients. A prospective study evaluating a screening test series with CRNIs in consecutive FD patients for 1 year was also conducted. These patients received a questionnaire for collecting extra characteristics (eg, concerning quality of life). RESULTS: Of 8740 tested patients, 2292 (26.2%) had FD. Of these, 30.6% had cosmetic-induced FD. The most common cosmetic-related allergens were fragrances and preservatives. The most common patch test-positive CRNIs were hydroperoxides of limonene and linalool, and propolis. Potato and peanut were rare, but the most common prick test-positive CRNIs, however, without any relation to the use of cosmetic products. FD affected nearly all patients' quality of life and caused limitations to their daily life. CONCLUSIONS: Updated management and quick diagnosis of FD is important to avoid negative impact on patients' quality of life.

The epidemic of contact allergy to methylisothiazolinone-An analysis of Danish consecutive patients patch tested between 2005 and 2019.

BACKGROUND: In 2005, methylisothiazolinone (MI) was allowed as a stand-alone preservative in cosmetics. This resulted in an epidemic of allergic contact dermatitis to MI, mainly affecting women exposed to leave-on cosmetics. Consequently, a regulation of Annex V in the European Union in 2017 banned the use of MI in leave-on cosmetics and reduced the allowed concentration in rinse-off products. OBJECTIVE: To analyze the temporal trends in contact allergy to MI in Danish patients in relation to key events including European regulations over time. METHODS: A retrospective study of consecutive patients patch tested with methylisothiazolinone from 2005 to 2019. Demographics and clinical characteristics in terms of MOAHLFA (male, occupational, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis and age >40 years), sources of exposure, and clinical relevance were analyzed in relation to key historical events. RESULTS: Three hundred eighty of 12 494 patients (3.0%, 95CI: 2.7-3.4%) tested from 2005 to 2019 were sensitized to MI. An increasing trend in the prevalence of MI contact allergy from 2005 to 2019 (P < .01) was observed, although a decline in the absolute number of patch-test positive patients was seen from 2013 and onward. A reduction in leave-on cosmetics as a source of exposure was observed following the legislative ban in 2017, from 24.8% from in 2010 to 2013 to 6.2% in 2017 to 2019 (P < .01). CONCLUSION: The epidemic of MI contact allergy is declining in absolute terms, although the prevalence in the patch-tested population has not returned to its pre-epidemic levels. The legislative regulation of MI in 2017 has been effective in terms of leave-on cosmetics as a source of exposure in MI allergic patients. The process of post-marketing risk assessment of contact allergens in the European Union needs improvement.

Papulopustular rosacea during nivolumab therapy of metastatic squamous cell esophageal carcinoma.

We present a 76-year old man who developed papulopustular rosacea after receiving nivolumab treatment for his esophageal carcinoma, metastatic to the lungs. Nivolumab is an emerging cancer therapy whose immune-related adverse events are still not fully recognized and likely underreported. The treatment has been reported to cause a myriad of cutaneous immune-related adverse events. However, nivolumab-induced-papulopustular rosacea has been scarcely reported. Thus, this case presents a clinically important finding that physicians should be aware of when seeing patients on nivolumab therapy.

Retrospective review of delayed adverse events secondary to treatment with a smooth, cohesive 20-mg/mL hyaluronic acid filler in 4500 patients.

BACKGROUND: Recent publications have suggested an increased risk of delayed adverse events (DAEs) with a smooth, cohesive 20-mg/mL hyaluronic acid filler, Juvéderm Voluma (HA-V). OBJECTIVE: To examine the occurrence of HA-V DAEs and identify patterns and characteristics. METHODS: Charts from patients who received HA-V between February 1, 2009, and February 28, 2018 from 2 clinics were analyzed. RESULTS: In 4500 patients who received 9324 treatments with HA-V, 44 DAEs were identified, for a combined incidence of 0.98% per patient, 0.47% per treatment, and 0.23% per syringe. Patients with DAEs received a slightly larger cumulative amount of HA-V than those who did not. Delayed swelling and nodule formation were the most common reactions and occurred a median of 4 months after treatment, with an increase in frequency between October and January. About a third were preceded by an identifiable immunologic stimulus. DAEs were transient and resolved without incident. LIMITATIONS: The retrospective nature made it difficult to capture time to resolution or remember potential triggers. CONCLUSION: In this large, long-term, retrospective review, HA-V DAEs occurred at a rate of 0.98% per patient. Although the exact cause has yet to be elucidated, we hypothesize that an increase in fragmentation during the HA-V degradation process may trigger an inflammatory response after an immunologic trigger.

Allergic and photoallergic contact dermatitis to chlorpromazine.

Chlorpromazine is known to produce both systemic phototoxic and photoallergic reactions. However, it may also cause photoallergic contact dermatitis and, albeit exceptionally, allergic contact dermatitis (ACD). We present a series of photoallergic contact dermatitis and ACD to chlorpromazine diagnosed at a tertiary centre cutaneous allergy unit between 1980 and 2019.

Delayed-Onset Nodules to Differentially Crosslinked Hyaluronic Acids: Comparative Incidence and Risk Assessment.

BACKGROUND: Robust and long-term data on true incidence of delayed-onset nodules and immune tolerance of hyaluronic acid (HA) fillers are lacking. OBJECTIVE: To characterize the incidence of delayed nodules in Vycross (VYC) HA fillers compared with previously reported FDA and non-FDA data of all HA fillers. METHODS AND MATERIALS: The incidence of delayed nodules in all patients who had received VYC fillers in a 12-month period was assessed through a retrospective chart review. Nodule incidence for currently approved nonanimal-stabilized hyaluronic acid (NASHA) fillers was assessed using the FDA Summary of Safety and Effectiveness Data. RESULTS: Overall, 1,029 patients received 1,250 VYC filler treatments. Five patients developed delayed nodules to VOB, with an incidence of 1.0% per patient and 0.8% per syringe. No nodules were observed in patients who received VLR or VOL. All nodules were treated successfully using a combination of intralesional triamcinolone and hyaluronidase. Compared with other currently approved NASHA fillers, VOB is associated with a higher incidence of nodule formation. CONCLUSION: The introduction of VYC HAs has introduced a new variable that may be changing the immune tolerance of these substances, resulting in a higher incidence of delayed nodules than previously expected.

Contact allergy to beeswax and propolis among patients with cheilitis or facial dermatitis.

BACKGROUND: Beeswax, both white and yellow, has many uses, such as in lip balm. This material can cause contact allergy, although not many cases have been described. METHODS: Ninety-five patients with contact cheilitis, facial eczema or a suspicion of contact allergy to beeswax were patch tested with yellow and white beeswax and with propolis, in addition to the Swedish baseline series. Patients who reacted positively to beeswax were additionally tested with caffeic acid, and two derivatives thereof that are believed to be important haptens in propolis. RESULTS: Seventeen patients had positive reactions to beeswax. Fourteen of these patients had been tested with both yellow and white beeswax. Among those 14, eight had positive reactions to both types of wax, five only to yellow wax, and one only to white wax. Of the 10 wax-positive patients tested with caffeic acid derivatives, three reacted positively. Fourteen beeswax-positive patients also had positive reactions to propolis. CONCLUSION: Patch testing cheilitis patients is important, as contact allergy is common. Our suggestion is to patch test, apart from the baseline series and the patient's own products, also with beeswax and propolis. Many beeswax-allergic cheilitis patients would not have been diagnosed with a relevant contact allergy if only the Swedish baseline series had been used.

European Surveillance System on Contact Allergies (ESSCA): Contact allergies in relation to body sites in patients with allergic contact dermatitis.

BACKGROUND: Analyses of the European Surveillance System on Contact Allergies (ESSCA) database have focused primarily on the prevalence of contact allergies to the European baseline series, both overall and in subgroups of patients. However, affected body sites have hitherto not been addressed. OBJECTIVE: To determine the prevalence of contact allergies for distinct body sites in patients with allergic contact dermatitis (ACD). METHODS: Analysis of data collected by the ESSCA (www.essca-dc.org) in consecutively patch tested patients, from 2009 to 2014, in eight European countries was performed. Cases were selected on the basis of the presence of minimally one positive patch test reaction to the baseline series, and a final diagnosis of ACD attributed to only one body site. RESULTS: Six thousand two hundred and fifty-five cases were analysed. The head and hand were the most common single sites that ACD was attributed to. Differences between countries were seen for several body sites. Nickel, fragrance mix I, cobalt and methylchloroisothiazolinone/methylisothiazolinone were the most frequent allergens reported for various body sites. CONCLUSIONS: Distinct allergen patterns per body site were observed. However, contact allergies were probably not always relevant for the dermatitis that patients presented with. The possibility of linking positive patch test reactions to relevance, along with affected body sites, should be a useful addition to patch test documentation systems.

Allergic contact dermatitis caused by topical ophthalmic medications: Keep an eye on it!

BACKGROUND: Allergic contact dermatitis (ACD) caused by topical ophthalmic medications is often overlooked. OBJECTIVES: To study the demographic characteristics, lesion locations and associated medical conditions of the patients with ACD caused by ophthalmic drugs, and to identify the most common allergenic culprits, as well as trends in frequencies over the years. METHODS: From January 1990 until December 2016, 16 065 patients were investigated in our clinic; all patients with a positive patch test reaction to an eye medication or its ingredient(s) having caused ACD were assessed. For each allergen identified, the number of positive test results as compared with the total number of those in the total population, as well as trends across three periods, namely 1990 to 1998, 1999 to 2007, and 2008 to 2016, were studied. RESULTS: One hundred and eighteen patients (0.7%) presented with positive patch test reactions to ingredients of and/or topical ophthalmic medications. Aminoglycoside antibiotics, followed by corticosteroids, as pharmacologically active ingredients, as well as wool alcohols, thiomersal, and benzalkonium chloride, as excipients, were the most frequent culprits. Chloramphenicol showed a decreasing trend of positive reactions over time, whereas reactions to tobramycin increased. CONCLUSION: ACD caused by eye medication is mainly attributable to active principles, but other excipient ingredients, beside the products "as is," should be tested as well.

Factors associated with multiple contact allergies in Thai dermatitis patients: A 10-year retrospective study.

BACKGROUND: Multiple contact allergies (MCAs) are defined as three or more positive patch test reactions to unrelated antigens. Factors associated with MCAs include female sex, older age, and certain eczema sites. OBJECTIVES: To investigate the prevalence of MCAs, risk factors for their development, and patterns of allergen combinations. METHODS: This retrospective, case-control study was conducted on patients suspected of having allergic contact dermatitis who had been patch tested with a baseline series in the period January 2007 to December 2016. RESULTS: Of the 2178 included patients, 531 (24.4%) had MCAs. A multivariate analysis showed that a generalized distribution of dermatitis represented the highest risk factor (odds ratio [OR] 3.97), followed by a history of metal allergy (OR 3.18). The other significantly associated factors were, in order of decreasing frequency, the dermatitis sites (hands/feet, extremities, and face), age ≥25 years, and occupationally related dermatitis; their ORs were <3. CONCLUSIONS: The factors that were significantly associated with MCAs were identified. The ranking of the common contact allergens among MCA patients was comparable with that of non-MCA patients. Metal and fragrance allergens were frequently found to cause concurrent positive reactions in MCA patients.

Exogenous ochronosis: the failure of depigmenting creams.

Exogenous ochronosis (EO) is an entity that manifests as black-bluish or grayish-brown cutaneous hyperpigmentation, which is a consequence of the deposition of ochronotic pigment with characteristic banana-like morphology between the collagen fibers of the dermis. Both the clinical presentation and histopathology appearance are superimposable with endogenous ochronosis or alcaptonuria, a hereditary disease in which ochronotic pigment deposition occurs at a multisystemic level. The most frequent cause of EO is the use of facial depigmenting creams containing hydroquinone, a common practice among women with high phototypes. We present a woman who developed EO on the face, upper chest, and back after prolonged use of a depigmenting cream containing hydroquinone.

[Vemurafenib-induced radiation recall dermatitis]. / Dermite de rappel induite par le vémurafénib.

INTRODUCTION: Radiation recall dermatitis is an uncommon inflammatory reaction of the skin appearing after several days to several years at the site of previous irradiation; it is precipitated by the use of triggering drugs, although rarely by BRAF or MEK inhibitors. PATIENTS AND METHODS: We report an unusual case of recall dermatitis induced 3 months after initiation of vemurafenib and cobimetinib therapy. DISCUSSION: Radiation recall dermatitis is a cutaneous reaction that must be known and which in rare cases such as ours may occur a long time after the end of radiotherapy.

Eruptive Sebaceous Hyperplasia: A Rare Consequence of Systemic Corticosteroids.

BACKGROUND: Eruptive sebaceous hyperplasia is a rare and poorly understood consequence of immunosuppression, most commonly with cyclosporine, following organ transplantation. To date, there have been no reports documenting eruptive sebaceous hyperplasia associated with the utilization of immunosuppression outside of this clinical scenario. OBSERVATION: A 43-year-old Caucasian male with a significant history for Crohn's disease presented with the sudden appearance of multiple asymptomatic growths now present for several weeks. They were first noted two weeks following the initiation of a slow prednisone taper prescribed for a recent exacerbation of Crohn's disease. Skin examination revealed multiple 1-3mm, soft, skin colored to yellowish, dome-shaped, umbilicated papules on the forehead and the bilateral lateral/malar cheeks, clinically suggestive and confirmed histologically as sebaceous hyperplasia. CONCLUSION: To our knowledge, this is the first reported case of eruptive sebaceous hyperplasia secondary to the use of prednisone in a patient with Crohn's disease. This case brings awareness to the unique side effect of prednisone induced sebaceous hyperplasia, and demonstrates the importance of educating patients with Crohn's disease of this potential side effect when prescribing this medication.

J Drugs Dermatol. 2018;17(1):118-120.