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african-american patient Archives | Skin of Color Update | Dermatology Conference | New York City

Black Male With Psoriasis and Dyspigmentation

Successful Management of a Black Male With Psoriasis and Dyspigmentation Treated With Halobetasol Propionate 0.01%/Tazarotene 0.045% Lotion: Case Report

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Introduction

Skin of color patients with psoriasis face unique challenges related to disease characteristics and treatment. Distribution and severity of psoriasis may be greater in patients with skin of color.1,2 Dyspigmentation—including postinflammatory hypo- and hyperpigmentation—also more frequently and severely affects patients with skin of color3,4 and remains a challenge for dermatologists to manage.5 Finally, Black and Hispanic/Latino patients have demonstrated worse health-related quality of life (QoL) compared with White patients, as assessed by the Dermatology Life Quality Index (DLQI)6; these differences are likely related to several factors, which include varying cultural perceptions of skin disorders and the greater negative impact of dyspigmentation in patients with skin of color.2,7 The treatment of psoriasis commonly involves the use of topical corticosteroids, such as the superpotent topical corticosteroid halobetasol propionate (HP).8,9 Corticosteroids are anti-inflammatory, immunosuppressive, antiproliferative, and vasoconstrictive; however, tachyphylaxis and adverse events following long-term use remain a concern.8-10 The topical retinoid tazarotene (TAZ) has several mechanisms of action that modulate pathogenic factors of psoriasis—including normalizing markers of differentiation, proliferation, and inflammation—though TAZ used alone may induce cutaneous irritation.10-13 The combination of HP with TAZ may enhance efficacy in the treatment of psoriasis, reduce side effects of both active drugs, and sustain treatment response.10,11

A fixed combination lotion of HP 0.01% and TAZ 0.045% (HP/TAZ; Duobrii,® Ortho Dermatologics, Bridgewater, NJ) was developed utilizing a novel polymeric emulsion technology, which allows for rapid and uniform distribution of HP and TAZ, humectants, and moisturizers on the skin.10 Phase 3 clinical data have demonstrated efficacy and tolerability of HP/TAZ lotion in patients with moderate-to-severe localized plaque psoriasis.14,15 Here, we present a case report of a Black male with moderate plaque psoriasis who was successfully treated with once-daily HP/TAZ lotion over 8 weeks, with resolution of skin dyspigmentation by week 12.

Psoriasis and Dyspigmentation in black male

 Click table to enlarge

Case Report

The patient was a 58-year-old, non-Hispanic, Black male with moderate psoriasis (Investigator’s Global Assessment [IGA]=3) and affected body surface area (BSA) of 10% at baseline (Table 1). The patient was enrolled in a phase 3, randomized, double-blind, vehicle-controlled study that assessed HP/TAZ lotion in participants with moderate-to-severe psoriasis (NCT02462070); detailed methodology and study results have been previously published.14,15 The patient, randomized to HP/TAZ for 8 weeks with a 4-week posttreatment follow-up, was instructed to apply a thin layer of HP/TAZ lotion once-daily over all affected areas. The target lesion (Figure 1), located on the upper right arm, was 99 cm2 in size at baseline; prominent keloid scars were also apparent. The patient also had an additional non-target lesion treated with HP/TAZ during the study (Figure 2). At baseline, both lesions appeared as classic psoriatic elevated plaques covered with white/silvery scales. By week 2 of HP/TAZ treatment, scales had diminished, though affected skin was hypopigmented in the center with hyperpigmentation at the border of the psoriatic plaque resolution. The degree of hypopigmentation appeared to be greatest at week 4, with skin pigmentation nearing normal by week 8. At 4 weeks posttreatment, the affected skin area had returned to normal with small regions of hyperpigmentation, the greatest around the periphery of the affected skin lesion.

FIGURE 1. Target lesion. Patient was treated with HP 0.01%/TAZ 0.045% lotion once daily for 8 weeks, with 4-week posttreatment follow-up at week 12.

Black Male With Psoriasis and Dyspigmentation

HP, halobetasol propionate; TAZ, tazarotene.

FIGURE 2. Additional lesion. Patient was treated with HP 0.01%/TAZ 0.045% lotion once daily for 8 weeks, with 4-week posttreatment follow-up at week 12.

Black Male With Psoriasis and Dyspigmentation

HP, halobetasol propionate; TAZ, tazarotene.

 

The patient achieved treatment success with HP/TAZ lotion, with an improvement to ‘almost clear’ at week 4 that was maintained posttreatment at week 12 (Table 1). Improvements in affected BSA and signs of psoriasis at the target lesion were also observed early following treatment with HP/TAZ lotion and maintained up to 4 weeks posttreatment. The patient had substantial improvements in QoL during the study, with DLQI score decreasing from 9 (“moderate effect” on life) at baseline to 1 (“no effect” on life) at weeks 4 and 8.

No adverse events were reported. Dryness was the only local skin reaction present at baseline (assessed as moderate by the investigator), which subsided at weeks 2–6 and returned to mild dryness by study end (Table 1). No itching was reported during HP/TAZ treatment until posttreatment follow-up, where it was assessed as moderate. The patient did not report burning/stinging at any study visit. Further, there were no instances of skin atrophy, striae, telangiectasias, or folliculitis—other known drug-related skin reactions.

Discussion

Racial and ethnic differences in epidemiology, clinical features, genetic predisposition, and response to treatment of psoriasis are important to address given our increasingly diverse patient population.7 Here we report the management of psoriasis in a Black male enrolled in a clinical trial who was randomized to treatment with HP 0.01%/TAZ 0.045% lotion once daily for 8 weeks, with a 4-week posttreatment follow-up at week 12.

HP/TAZ was efficacious in this patient, who achieved an IGA score of 1 (almost clear) within 4 weeks and maintained treatment success at weeks 8 and 12. Affected BSA decreased 50% from baseline to week 8. Quality of life was improved in this patient, whose DLQI score by week 8 indicated “no effect” of psoriasis on the patient’s QoL, a substantial and clinically meaningful16 improvement from the “moderate effect” observed at baseline. A clinical feature of this patient was the presence of prominent keloid scars, which are benign fibrous growths resulting from an abnormal connective tissue response.17 While the cause of the keloids in this patient is not known, the presence of keloids is not unexpected, as there are racial differences in prevalence, with Black individuals forming keloids more often than White individuals.17

The patient experienced dyspigmentation of the affected skin during the trial, which is also not unexpected, given that resolution of psoriasis in darker skin is associated with both hypo- and hyper-pigmentation.18 Dyspigmentation is of particular concern, as it can have significant psychosocial impacts, contribute to greater negative emotions, and even be more bothersome than the psoriasis itself in patients with skin of color.2,4,7 Hypopigmentation was primarily experienced from weeks 2-8, with the greatest degree at week 4. By week 12 the affected skin area had returned to normal, with only small regions of hyperpigmentation, primarily around the periphery of the lesion. This relatively fast time to resolution is notable given that dyspigmented patches can take between 3 and 12 months to resolve.2

Skin color is primarily due to the presence of melanin, a pigment formed by immune cells called melanocytes. Melanin formation, or melanogenesis, is a complex process of melanin synthesis, transport, and release to keratinocytes, which occurs within organelles of melanocytes called melanosomes.19 The mechanisms and pathogenesis of postinflammatory hypo- and hyperpigmentation in psoriasis are not fully elucidated, though multiple hypotheses have been suggested. Inflammation-associated hypopigmentation may be a result of rapid turnover of keratinocytes during hyperplasia, which can interfere with melanosome transfer.18 Cutaneous inflammation, through signaling of growth factors and pro-inflammatory cytokines such as IL-17 and TNF-α, can also lead to hypopigmentation through inhibition of melanogenesis, 18,20 with more severe inflammation potentially leading to permanent pigmentary changes through loss or death of melanocytes.20 Interestingly, it has been observed that while hypopigmentation often accompanies active inflammation, patients are at risk of developing hyperpigmentation once the inflammation has resolved, potentially due to increased numbers and activity of melanocytes.18,21 This too may be the result of cytokine signaling during inflammation. For example, IL-17 and TNF-α can simultaneously suppress melanogenesis while also stimulating the proliferation of melanocytes; as such, upon resolution of inflammation, the increased number of melanocytes in lesional skin (without concurrent suppression of melanogenesis) will produce excess melanin, leading to postinflammatory hyperpigmentation.18

The fixed combination of HP and TAZ used to treat psoriasis in the patient from this case report resulted in psoriasis lesion clearance with self-limited postinflammatory hypopigmentation and low levels of hyperpigmentation observed by week 12. Topical corticosteroids, a mainstay of treatment for psoriasis,8 are used as first-line therapy for hyperpigmentation when combined with hydroquinone and topical retinoids.5,22 Corticosteroids are thought to be effective by decreasing cellular metabolism, thereby inhibiting melanin synthesis.22 Corticosteroids have also been shown to minimize the risk of postinflammatory hyperpigmentation after laser resurfacing.23 Topical retinoids are effective in treating postinflammatory hyperpigmentation with other agents as described above or as monotherapy.22 For example, TAZ 0.1% gel and cream have demonstrated efficacy in acne-related postinflammatory hyperpigmentation, significantly improving pigmentation intensity versus vehicle24,25; TAZ was also more effective than adapalene 0.3% gel in reducing hyperpigmentation.25 Tazarotene 0.1% cream is approved as an adjunctive treatment in the mitigation of facial mottled hyper- and hypopigmentation. Retinoids are thought to reduce hyperpigmentation through multiple mechanisms, including: stimulating keratinocyte turnover (promoting loss of melanin), reducing/inhibiting melanosome transfer to keratinocytes, and interrupting melanin synthesis.22,26 TAZ has also been shown to downregulate markers of cell proliferation and inflammation such as IL-6,12,13 which is known to have hypopigmenting effects.18

The fixed combination HP 0.01%/TAZ 0.045% lotion used by the patient in this case report has additional efficacy and safety benefits. The new polymeric emulsion technology used to develop HP/TAZ lotion allows for efficient permeation of the active ingredients into the dermal layers, at around half the concentration of traditional topical formulations.10 Further, HP/TAZ lotion has demonstrated synergistic activity, with efficacy greater than that which would be predicted from the individual active ingredients.10 The maintenance of therapeutic effect seen in this patient—who sustained disease reduction 4 weeks posttreatment—is likely due to the mechanism of action of TAZ in psoriasis, which restores skin to a quiescent, prelesional status.27 However, when used alone, TAZ can cause cutaneous irritation; HP alone can also result in AEs that limit long term use. These safety limitations can be minimized when combining HP with TAZ.10,11 The patient in this case report did not report any adverse events—including any application or irritation events—and local skin reactions were limited. Though the patient was limited to 8-weeks of HP/TAZ treatment as part of the clinical trial design, treatment with HP/TAZ for up to 1 year (maximum 24 weeks of continuous use) in an open-label, long-term study (NCT02462083) has demonstrated a favorable safety profile.28

Conclusion

In conclusion, this case report in a Black male patient demonstrates that this new formulation of HP 0.01%/TAZ 0.045% lotion was efficacious in the treatment of psoriasis, with treatment success achieved early and maintained 4 weeks posttreatment. Hypopigmentation was evident during resolution of disease, though had completely resolved by week 12 with minimal hyperpigmentation observed. These results indicate that HP/TAZ may be a treatment option for patients with skin of color, who are disproportionally affected by postinflammatory dyspigmentation.

Disclosures

Seemal Desai has served as a research investigator and/or consultant for Skinmedica, Ortho Dermatologics, Galderma, Pfizer, Dermavant, Almirall, Dermira, and Watson.

Andrew F. Alexis has received grant/research support (funds to institution) from Leo, Novartis, Almirall, Bristol-Myers-Squibb, Celgene, Menlo, Galderma, Bausch Health, and Cara; and has served as a consultant/advisory board member for Leo, Novartis, Menlo, Galderma, Pfizer, Sanofi-Regeneron, Dermavant, Unilever, Celgene, Beiersdorf, L’Oreal, BMS, Menlo, Scientis, Bausch Health, UCB, and Foamix.

Abby Jacobson is an employee of Ortho Dermatologics and may hold stock and/or stock options in its parent company.

Acknowledgements

The studies were funded by Ortho Dermatologics. Medical writing support was provided by Prescott Medical Communications Group (Chicago, IL) with financial support from Ortho Dermatologics. Ortho Dermatologics is a division of Bausch Health US, LLC.

References

1. Gelfand JM, Stern RS, Nijsten T, et al. The prevalence of psoriasis in African Americans: Results from a population-based study. J Am Acad Dermatol. 2005;52(1):23-26.
2. Alexis AF, Blackcloud P. Psoriasis in skin of color: Epidemiology, genetics, clinical presentation, and treatment nuances. J Clin Aesthet Dermatol. 2014;7(11):16-24.
3. Alexis AF, Sergay AB, Taylor SC. Common dermatologic disorders in skin of color: A comparative practice survey. Cutis. 2007;80(5):387-394.
4. Davis EC, Callender VD. Postinflammatory hyperpigmentation: A review of the epidemiology, clinical features, and treatment options in skin of color. J Clin Aesthet Dermatol. 2010;3(7):20-31.
5. Desai SR. Hyperpigmentation therapy: a review. J Clin Aesthet Dermatol. 2014;7(8):13-17.
6. Shah SK, Arthur A, Yang YC, et al. A retrospective study to investigate racial and ethnic variations in the treatment of psoriasis with etanercept. J Drugs Dermatol. 2011;10(8):866-872.
7. Kaufman BP, Alexis AF. Psoriasis in skin of color: Insights into the epidemiology, clinical presentation, genetics, quality-of-life impact, and treatment of psoriasis in non-White racial/ethnic groups. Am J Clin Dermatol. 2018;19(3):405-423.
8. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol. 2009;60(4):643-659.
9. Uva L, Miguel D, Pinheiro C, et al. Mechanisms of action of topical corticosteroids in psoriasis. Int J Endocrinol. 2012;2012:561018.
10. Tanghetti EA, Stein Gold L, Del Rosso JQ, et al. Optimized formulation for topical application of a fixed combination halobetasol/tazarotene lotion using polymeric emulsion technology. J Dermatolog Treat. 2019:1-8.
11. Tanghetti E, Lebwohl M, Stein Gold L. Tazarotene revisited: Safety and efficacy in plaque psoriasis and its emerging role in treatment strategy. J Drugs Dermatol. 2018;17(12):1280-1287.
12. Duvic M, Nagpal S, Asano AT, Chandraratna RA. Molecular mechanisms of tazarotene action in psoriasis. J Am Acad Dermatol. 1997;37(2 Pt 3):S18-24.
13. Duvic M, Asano AT, Hager C, Mays S. The pathogenesis of psoriasis and the mechanism of action of tazarotene. J Am Acad Dermatol. 1998;39(4 Pt 2):S129-133.
14. Gold LS, Lebwohl MG, Sugarman JL, et al. Safety and efficacy of a fixed combination of halobetasol and tazarotene in the treatment of moderate-to-severe plaque psoriasis: Results of 2 phase 3 randomized controlled trials. J Am Acad Dermatol. 2018;79(2):287-293.
15. Sugarman JL, Weiss J, Tanghetti EA, et al. Safety and efficacy of a fixed combination halobetasol and tazarotene lotion in the treatment of moderate-to-severe plaque psoriasis: A pooled analysis of two phase 3 studies. J Drugs Dermatol. 2018;17(8):855-861.
16. Basra MK, Salek MS, Camilleri L, et al. Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): Further data. Dermatology. 2015;230(1):27-33.
17. Kelly AP. Keloids. Dermatol Clin. 1988;6(3):413-424.
18. Wang CQF, Akalu YT, Suarez-Farinas M, et al. IL-17 and TNF synergistically modulate cytokine expression while suppressing melanogenesis: Potential relevance to psoriasis. J Invest Dermatol. 2013;133(12):2741-2752.
19. Wasmeier C, Hume AN, Bolasco G, Seabra MC. Melanosomes at a glance. J Cell Sci. 2008;121(Pt 24):3995-3999.
20. Vachiramon V, Thadanipon K. Postinflammatory hypopigmentation. Clin Exp Dermatol. 2011;36(7):708-714.
21. Abdel-Naser MB, Liakou AI, Elewa R, et al. Increased activity and number of epidermal melanocytes in lesional psoriatic skin. Dermatology. 2016;232(4):425-430.
22. Vashi NA, Kundu RV. Facial hyperpigmentation: Causes and treatment. Br J Dermatol. 2013;169 Suppl 3:41-56.

Originally published in the Journal of Drugs in Dermatology in October 2020. 

Desai, S. R., Alexis, A. F., & Jacobson, A. (2020). Successful Management of a Black Male With Psoriasis and Dyspigmentation Treated With Halobetasol Propionate 0.01%/Tazarotene 0.045% Lotion: Case Report. Journal of drugs in dermatology: JDD, 19(10), 1000-1004. https://jddonline.com/articles/dermatology/S1545961620P1000X

Content and images republished with permission from the Journal of Drugs in Dermatology.

Adapted from original article for length and style.

The Journal of Drugs in Dermatology is available complimentary to US dermatologists, US dermatology residents, and US dermatology NP/PA. Create an account on JDDonline.com and access over 15 years of PubMed/MEDLINE archived content.

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Cutaneous Sarcoidosis

Hypopigmented Cutaneous Sarcoidosis Responsive to Minocycline

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Hypopigmented patches and plaques are a rare presentation of cutaneous sarcoidosis. JDD authors describe a case of generalized hypopigmented cutaneous sarcoidosis that showed good response to minocycline therapy.

Introduction

A 58-year-old African-American male with a past medical history of hypertension, diabetes mellitus, tobacco use, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and hyperlipidemia presented with a two-year history of asymptomatic light spots on his trunk and upper extremities. He reported a history of cutaneous sarcoidosis a decade prior, characterized by erythematous papules and plaques that had regressed with hydroxychloroquine therapy. The newer light patches were not responsive to mid-potency topical steroids or tacrolimus 0.1% ointment. Review of systems was negative. The patient denied any new medications or history of travel outside of the metropolitan area.

 

Physical examination of the skin was significant for multiple hypopigmented patches on the face, neck, and extremities; hypopigmented plaques on the back (Figure 1); and annular plaques of hypopigmented papules on the chest and abdomen (Figure 2). The lesions were not hypoesthetic. There was no lymphadenopathy and physical exam was otherwise unremarkable.

 

A biopsy from the left arm showed a superficial and deep multinodular granulomatous infiltrate sparing the epidermis (Figure 3). The granulomas were predominantly composed of epithelioid histiocytes with a few scattered lymphocytes (Figure 4). Special stains for microorganisms were negative. There was no appreciable epidermal change or pigment incontinence. The histopathological picture was consistent with recurrent cutaneous sarcoidosis.
Computed tomography of the chest with and without contrast showed no evidence of active pulmonary sarcoidosis or lymphadenopathy. An ophthalmologic exam, abdominal ultrasound, and spirometry were within normal limits, as were serum cal cium and angiotensin-converting enzyme (ACE) levels.

 

Because the patient’s skin manifestations had resolved with hydroxychloroquine in the past, this treatment was restarted at 200 mg twice-daily. Unfortunately, laboratory monitoring revealed hepatic transaminitis and mild anemia 2 months into the treatment course, corresponding with only minimal improvement of the hypopigmented plaques, necessitating discontinuation of hydroxychloroquine. Minocycline at a dose of 100 mg twice daily was then initiated 4 months after normalization of liver function tests. After 5 months of treatment, all hypopigmented patches, papules, and plaques had completely or partially repigmented and were appreciably smoother and flatter (Figures 5 and 6). The patient tolerated the medication well with no adverse effects.

 

Cutaneous Sarcoidosis

FIGURE 1. Hypopigmented plaques over the back.

Cutaneous Sarcoidosis

FIGURE 2. Hypopigmented annular plaques of papules on the abdomen.

Cutaneous Sarcoidosis

FIGURE 3. Hematoxylin and eosin stain of a left arm skin biopsy show-ing dermal granulomatous inflammation.

Cutaneous Sarcoidosis

FIGURE 4. Hematoxylin and eosin stain of a left arm skin biopsy at higher magnification demonstrating well-formed naked granulomas.

Cutaneous Sarcoidosis

FIGURE 5. Flattening and repigmentation of plaques on the back after treatment with minocycline.

Cutaneous Sarcoidosis

FIGURE 6. Repigmentation of annuli on the anterior trunk after treat-ment with minocycline.

 

Discussion

The skin is one of myriad organs potentially affected by sarcoidosis, a multisystem idiopathic disorder characterized histologically by infiltration of noncaseating granulomas. Cutaneous manifestations of sarcoidosis are protean, including papules and plaques of various morphology and distribution, subcutaneous nodules, pruritus, ichthyosis, erythroderma, ulceration, verrucosis, nail disease, and infiltrative scars.1 In the United States, sarcoidosis is more common in African-Americans than in other ethnic groups, and cutaneous manifestations in individuals of African descent are more likely to be atypical.2

In 1973, Cornelius et al reported 4 patients who presented with hypopigmented and depigmented patches and plaques that showed the naked tuberculoid granulomas characteristic of sarcoidosis on skin biopsy.3 The distribution in these cases was variable, with generalization in one patient and localization to the face, legs only, or legs and arms in the other three. Histologically, no difference in epidermal melanocyte count was noted between affected and unaffected skin, but relative hypomelanosis of the malphigian and corneal layers was appreciated. All patients had multisystem disease. Four years later, Hubler described a “hypomelanotic canopy” in a woman with lupus pernio and lymphadenopathy whose hypopigmented patches overlay deep subcutaneous nodules on the arms.4Biopsy of an enlarged lymph node revealed epithelioid granulomas that were reduplicated on skin biopsy. Interestingly, cutaneous hypopigmentation lacking any histological evidence of granulomatous dermatitis has also been observed in the setting of systemic sarcoidosis;5,6 this highlights the need for vigilant continued surveillance when the clinical index of suspicion for sarcoidosis is high and biopsy is noncorroborative.

 

The etiopathogenesis of hypopigmentation in sarcoidosis, like the disease itself, is unknown. Theories regarding the likely mul tifactorial cause of sarcoidosis center around T-cell—mediated autoimmunity, genetic predisposition, and aberrant response to bacterial or other antigens; the evidence for each has been extensively reviewed elsewhere.1,7 The rare cutaneous hypopigmentation seen in dark-skinned individuals with sarcoidosis appears to represent a melanopenic hypomelanosis, as opposed to postinflammatory hypopigmentation or melanocytopenia.3,4,8 In our patient, there were no epidermal changes, interface in flammation, or melanin-containing dermal macrophages to suggest postinflammatory dyspigmentation.

 

Minocycline represents an attractive alternative treatment for chronic sarcoidosis in patients who might otherwise be treated with long-term corticosteroids, antimalarials, methotrexate, or other immunosuppressants. The tetracycline class of antibiotics has previously demonstrated utility in a variety of dermatoses and autoimmune-connective tissue diseases, and may be particularly efficacious for granulomatous skin conditions.9,10 Tetracyclines have specifically shown efficacy in the treatment of granulomatous periorificial dermatitis, cheilitis granulomatosa, granulomatous rosacea, and silicone granulomas.11-14 More recently, tetracyclines proved beneficial in treating granuloma annulare (GA), an entity often with significant clinicopathological overlap with cutaneous sarcoidosis.15,16 Marcus et al showed that, in combination with rifampin and ofloxacin, 3 to 5 courses of monthly minocycline therapy led to complete clearance of GA in 6 patients, half of whom had generalized disease.15 In this series, the rationale for selection of the same triple combination antimicrobial therapy as that used for paucibacillary leprosy (PBL) was that the clinical and histological similarities between PBL and GA might impart an equally similar response to treatment. The same logic could be extrapolated further to include patients with cutaneous sarcoidosis as candidates for a treatment regimen, including minocycline, with or without rifampin and ofloxacin.

 

Minocycline as monotherapy was efficacious for the treatment of chronic cutaneous sarcoidosis in an open observational study of 12 patients by Bachelez et al.17 The cutaneous manifestations of patients in the Bachelez group included classic plaques, papulonodules, subcutaneous nodules, and lupus pernio. Ten of 12 patients completely or partially responded to treatment, which was generally well tolerated except for drug hypersensitivity syndrome in one patient with a history of other autoimmune diseases. Park et al later reported a patient with cutaneous, lacrimal gland, pulmonary, and ocular (choroidal) sarcoidosis that responded to minocycline.18

Miyazaki et al described a patient with a unique presentation of muscular sarcoidosis of the limbs, as well as uveitis and pulmonary disease, in whom clinical response to minocycline was paralleled by normalization of an elevated ACE level.19 The patient relapsed off of minocycline, but rapidly responded to reintroduction of the medication. Immunohistochemical staining of muscle biopsy specimens for Propionibacterium acnes showed multiple small particles within granuloma macrophages and giant cells, substantiating the theory that sarcoidosis is an infectious disease or an aberrant immunologic response to bacteria. Evidence for the role of other infectious agents in sarcoidosis, especially Mycobacterium tuberculosis, has been mixed and inconclusive.20 That sarcoidosis is purely an infectious disease is certainly within the realm of possibility,21 but the recurrence of disease once antibiotics are discontinued argues against this theory.19 An alternative explanation is that the benefits of tetracyclines in sarcoidosis and other autoimmune diseases are derived more from their nonantibiotic immunomodulating properties. The anti-inflammatory properties ascribed to minocycline include inhibition of T cell activation, proliferation, and transmigration as well as expression of nitric oxide synthetase and matrix metallopeptidase 9 (MMP-9).9Furthermore, tetracyclines have been shown to inhibit granuloma formation in vitro.22

 

Conclusion

The role of tetracyclines in the therapeutic armamentarium of sarcoidosis, especially in those who cannot tolerate antimalarials or other immunomodulating medications, is likely to expand. Whether minocycline is particularly effective for the hypopigmented variety of cutaneous sarcoidosis remains to be seen.

 

Disclosures

The authors have no relevant conflicts of interest to disclose.

References

  1. English JC 3rd, Callen JP. Sarcoidosis. In: Callen JP, Jorizzo JL, Bolognia JL, et al, eds. Dermatological Signs of Internal Disease. 4th ed. China: Elsevier; 2009:287-295.
  2. Jayck WK. Cutaneous sarcoidosis in black South Africans.Int J Dermatol. 1999;38(11):841-845.
  3. Cornelius CE 3rd, Stein KM, Hanshaw WJ, Spott DA. Hypopigmentation and sarcoidosis. Arch Dermatol.1973;108(2):249-251.
  4. Hubler WR Jr. Hypomelanotic canopy of sarcoidosis. Cutis.1977;19(1):86-88.
  5. Alexis JB. Sarcoidosis presenting as cutaneous hypopigmentation with repeatedly negative skin biopsies.Int J Dermatol. 1994;33(1):44-45.
  6. Hall RS, Floro JF, and King LE Jr. Hypopigmented lesions in sarcoidosis. J Am Acad Dermatol. 1984;11(6):1163-1164.
  7. English JC 3rd, Patel PJ, Greer KE. Sarcoidosis. J Am Acad Dermatol. 2001;44(5):725-743.
  8. Clayton R, Breathnach A, Martin B, et al. Hypopigmented sarcoidosis in the Negro. Report of eight cases with ultrastructural observations. Br J Dermatol.1977;96(2):119-125.
  9. Sapadin AN, Fleischmajer R. Tetracyclines: nonantibiotic properties and their clinical implications. J Am Acad Dermatol. 2006;54(2):258-265.
  10. Stone M, Fortin PR, Pacheco-Tena C, Inman, RD. Should tetracycline treatment be used more extensively for rheumatoid arthritis? Metaanalysis demonstrates clinical benefit with reduction in disease activity J Rheumatol.2003;30(10):2112-2122.
  11. Falk ES. Sarcoid-like granulomatous periocular dermatitis treated with tetracycline. Acta Derm Venereol.1985;65(3):270-272.
  12. Camacho F, García-Bravo B, and Carrizosa A. Treatment of Miescher’s cheilitis granulomatosa in Melkersson-Rosenthal syndrome. J Eur Acad Dermatol Venereol.2001;15(6):546-549.
  13. Mullanax MG, Kierland RR. Granulomatous rosacea. Arch Dermatol. 1970;101(2):206-211.
  14. Senet P, Bachelez H, Ollivaud L, Vignon-Pennamen D, Dubertret L. Mi- nocycline for the treatment of cutaneous silicone granulomas. Br J Dermatol. 1999;140(5):985-987.
  15. Marcus DV, Mahmoud BH, Hamzavi IH. Granuloma annulare treat- ed with rifampin, ofloxacin, and minocycline combination therapy Arch Dermatol. 2009;145(7):787-789.
  16. Duarte AF, Mota A, Pereira MA, Baudrier T, Azevedo F. Generalized granuloma annulare—response to doxycycline.J Eur Acad Derma- tol Venereol. 2009;23(1):84-85.
  17. Bachelez H, Senet P, Cadranel J, Kaoukhov A, Dubertret L. The use of tetracyclines for the treatment of sarcoidosis.Arch Dermatol. 2001;137(1):69-73.
  18. Park DJ, Woog JJ, Pulido JS, Cameron JD. Minocycline for the treatment of ocular and ocular adnexal sarcoidosis.Arch Ophthal- mol. 2007;125(5):705-709.
  19. Miyazaki E, Ando M, Fukami T, Nureki S, Eishi Y, Kumamoto T. Mi- nocycline for the treatment of sarcoidosis: Is the mechanism of action immunomodulating or antimicrobial effect? Clin Rheumatol. 2008;27(9):1195-1197.
  20. Tchernev G. Cutaneous sarcoidosis: the “great imitator”: etiopathogenesis, morphology, differential diagnosis, and clinical management. Am J Clin Dermatol. 2006;7(6):375-382.
  21. Marshall TG, Marshall FE. Sarcoidosis succumbs to antibiotics—implications for autoimmune disease.Autoimmun Rev.
  22. Webster GF, Toso SM, and Hegemann L. Inhibition of a model of in vitro granuloma formation by tetracyclines and ciprofloxacin. Involvement of protein kinase C. Arch Dermatol. 1994;130(6):748-752.

Originally published in the Journal of Drugs in Dermatology in April 2012. 

Schmitt, C. E., Fabi, S. G., Kukreja, T., & Feinberg, J. S. (2012). Hypopigmented cutaneous sarcoidosis responsive to minocycline. Journal of drugs in dermatology: JDD, 11(3), 385-389. https://jddonline.com/articles/dermatology/S1545961612P0385X  

Content and images republished with permission from the Journal of Drugs in Dermatology.

Adapted from original article for length and style.

The Journal of Drugs in Dermatology is available complimentary to US dermatologists, US dermatology residents, and US dermatology NP/PA. Create an account on JDDonline.com and access over 15 years of PubMed/MEDLINE archived content.

Did you enjoy this case report? You can find more here.

Pemphigus Foliaceus

Psoriasiform Pemphigus Foliaceus in an African American Female: An Important Clinical Manifestation

By | Case Reports, SOC Manuscripts | No Comments

JDD authors document and highlight this atypical psoriasiform presentation of Pemphigus Foliaceus in a patient with skin of color to raise awareness and improve diagnosis and outcomes.

Case Report

A 50-year-old African-American woman presented to the dermatology clinic with a pruritic eruption of 3 years’ duration that began as discrete plaques on the inframammary folds and subsequently spread towards the mid-chest, ears, back, elbows, knees, and scalp. Past treatments by other clinicians included clotrimazole cream and a topical corticosteroid of unknown potency without significant improvement. She denied any new medications and was taking aspirin, divalproex, mirtazapine, cetirizine, venlafaxine, atorvastatin, and omeprazole.

On clinical examination, the patient had well-demarcated, pink, atrophic plaques and superficial erosions over the inframammary folds and mid-chest (Figures 1). She also had well-demarcated, hyperpigmented, hyperkeratotic scaly plaques over the abdomen, suprapubic region, elbows, knees, and back with sporadic small superficial blisters (Figure 2). Complete blood count, complete metabolic panel, rheumatoid factor, and antinuclear antibody were within normal limits. Rapid plasma reagin test was negative. Erythrocyte sedimentation rate was elevated at 54 millimeter/hour (reference range 0-22 millimeter/hour). A punch biopsy of the right abdomen was performed and revealed psoriasiform epidermal hyperplasia, focal parakeratosis, and acantholysis throughout the superficial spinous and granular layers (Figure 3). Only a sparse inflammatory infiltrate was present in the underlying dermis. These clinical and histological findings supported the diagnosis of pemphigus foliaceus (PF). Patient was started on 50 mg oral dapsone daily.

Pemphigus Foliaceus

FIGURE 1. Well-demarcated, scaly plaques over the mid-chest and inframammary folds, with a single superficial erosion on the right medial chest.

Pemphigus Foliaceus

FIGURE 2. A plaque from the abdomen demonstrates “corn flake-like” scale.

Pemphigus Foliaceus

FIGURE 3. Composite photomicrograph, hematoxylin, and eosin, original magnification x200.

 

Discussion

Herein, we present a case of Pemphigus Foliaceus with a psoriasiform clinical presentation in an African-American patient. PF is an autoimmune skin disease caused by antibodies against the desmosomal glycoprotein, desmoglein 1.¹ Desmogleins, members of the cadherin family, serve to anchor epidermal desmosomes between adjacent keratinocytes and assist in epithelial differentiation.² Antibodies targeting desmoglein 1 result in acantholysis in the upper epidermis with limited separation in the basal layers and minimal mucosal involvement as desmoglein 1 is primarily expressed in the granular layer of the non-mucosal epidermis.¹ Patients present with scaly plaques on an erythematous base and fragile shallow blisters which are infrequently found intact; rarely, the condition can progress to exfoliative erythroderma.1,3 Initially, PF usually presents on the trunk, face, or scalp, but may subsequently involve other regions of the skin.1 Diagnosis may be confirmed with biopsy and direct immunofluorescence with intercellular IgG and C3 limited to the upper epidermis. Treatment includes oral and topical steroids, azathioprine, dapsone, and rituximab. The differential diagnosis for PF may include systemic lupus erythematosus, bullous impetigo, psoriasis, and seborrheic keratosis depending on the presentation.1

Physical exam findings in this patient were suggestive of PF due to the presence of superficial secondary erosions and “corn flake-like” scales, but psoriasis was included in the differential diagnosis due to the presence of discrete plaques with an erythematous border. PF is a relatively rare condition with a prevalence of less than 1 case per 100,000 and is about 5 to 10 times less common than pemphigus vulgaris.4 In contrast, psoriasis impacts approximately 2-4% of people in the United States.5 An endemic form of PF, fogo selvagem, has been reported in Brazil, Colombia, Peru, and Tunisia, while pemphigus vulgaris is more common in Mediterranean and Ashkenazi Jewish populations.4

We hypothesize that patients with psoriasiform presentations of PF may be misdiagnosed with plaque psoriasis. One author (JJ) has previous significant clinical experience with patients with skin of color and has seen other skin of color patients present with a psoriasiform manifestation of PF. PF and psoriasis share similar treatments including topical corticosteroids and immunosuppressants, and this may lead to underreporting of PF with psoriasiform manifestations. It is important to distinguish between these findings as there is evidence that ultraviolet light, a common treatment for psoriasis, may exacerbate PF.6,7 We performed a search of the published literature and identified one article that describes three patients with pemphigus erythematosus, a variant of PF, which was misdiagnosed as psoriasis.8 No identified articles described cases of PF with a psoriasiform presentation in patients with skin of color. We document and highlight this atypical psoriasiform presentation of PF in a patient with skin of color to raise awareness and improve diagnosis and patient outcomes.

Disclosures

The authors have no relevant disclosures. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. This material is the result of work supported with resources and the use of facilities at the Sacramento VA Medical Center.

 

References

  1. James KA, Culton DA, Diaz LA. Diagnosis and clinical features of pemphigus foliaceus. Dermatol Clin. 2011;29(3):405-412, viii.
  2. Simpson CL, Patel DM, Green KJ. Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis. Nat Rev Mol Cell Biol. 2011;12(9):565-580.
  3. Kershenovich R, Hodak E, Mimouni D. Diagnosis and classification of pemphigus and bullous pemphigoid. Autoimmun Rev. 2014;13(4):477-481.
  4. Meyer N, Misery L. Geoepidemiologic considerations of auto-immune pemphigus. Autoimmun Rev. 2010;9(5):A379-A382.
  5. Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70(3):512-516.
  6. Ruocco V, Ruocco E, Schiavo AL, Brunetti G, Guerrera LP, Wolf R. Pemphigus: Etiology, pathogenesis, and inducing or triggering factors: Facts and controversies. Clin Dermatol. 2013;31(4):374-381.
  7. Aghassi D, Dover JS. Pemphigus foliaceus induced by psoralen-UV-A. Arch Dermatol. 1998;134(10):1300-1301.
  8. Oktarina DA, Poot AM, Kramer D, Diercks GF, Jonkman MF, Pas HH. The IgG “lupus-band” deposition pattern of pemphigus erythematosus: association with the desmoglein 1 ectodomain as revealed by 3 cases. Arch Dermatol. 2012;148(10):1173-1178.

Originally published in the Journal of Drugs in Dermatology in April 2018. 

Evan Austin BS, Jillian W. Millsop MD, Haines Ely MD, Jared Jagdeo MD MS, and Joshua M. Schulman MD (2018). Psoriasiform Pemphigus Foliaceus in an African American Female: An Important Clinical Manifestation. Journal of Drugs in Dermatology, 17(14), 471-473. https://jddonline.com/articles/dermatology/S1545961618P0471X 

Content and images republished with permission from the Journal of Drugs in Dermatology.

Adapted from original article for length and style.

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