Krista Reznik

July 2020 Case Study

A 53-year-old male with history of HIV (CD4 count 150) presents to clinic for the following rash of body for the last 3 weeks. He states condition initially presented with a few papules over upper back and spread to include entire back, bilateral upper arms, and face. All lesions are asymptomatic. He denies fevers, chills, or recent travel. At initial visit, the following biopsy was performed and bacilli were identified on Warthin-Starry stain.

Based on clinical and histopathologic findings, what is the first line treatment?

A.) Griseofulvin
B.) Erythromycin
C.) Cephalexin
D.) Ciprofloxacin
E.) Valacyclovir

Correct Answer: B.) Erythromycin

A) Incorrect. Griseofulvin is an antifungal agent that prevents dermatophyte mitosis via tubulin inhibition. It is primarily utilized for pediatric patients to treat tinea capitis caused by Microsporum canis.¹

B) Correct. The clinical and histopathologic findings for this case are consistent with bacillary angiomatosis. Erythromycin, a macrolide antibiotic, is the first line therapy for treatment.² Macrolides inhibit bacterial synthesis by binding to the 50s ribosomal subunit.¹ Additionally, they are well known CYP3A4 inhibitors, which can increase risk for torsade de pointes when combined with other medications.² Thus, it is important to review patient medications prior to starting macrolides.

C) Incorrect. Cephalexin is a first generation cephalosporin that treats streptococcal and staphylococcal infections such as uncomplicated cellulitis, impetigo, or furuncolosis.² Common side effects include GI upset and hypersensitivity reactions. About 5-10% of penicillin-allergic patients can experience crossreactivity with cephalosporin use.¹

D) Incorrect. Ciprofloxacin is a first generation fluoroquinolone with gram-negative coverage.¹ This class of antibiotics interferes with DNA synthesis via inhibition of DNA gyrase and topoisomerase IV.¹ Side effects of fluoroquinolones include GI upset, tendinitis, tendon rupture, and photosensitivity.¹ Ciprofloxacin can be used to treat Oroya fever rather than bacillary angiomatosis.²

E) Incorrect. Valacyclovir is an antiviral agent used to treat herpes simplex infections and varicella-zoster infections. It is a prodrug of acyclovir with increased bioavailability.¹ Valacyclovir is generally well tolerated with minimal side effects. Rarely, immunosuppressed patients can experience thrombotic thrombocytopenic purpura or hemolytic uremic syndrome with use of valacylovir.²

Bacillary angiomatosis is one of the several conditions caused by Bartonella infections. There are over thirty species of these gram-negative bacilli, but only three species are known to affect humans – B. henslae, B. quintana, B bacilliformis.² Other diseases associated with Bartonella infections include cat scratch disease, Oroya fever, verruga peruana, Carrion disease, endocarditis, and bacillary peliosis.²

Bacillary angiomatosis is commonly seen in immunosuppressed states, such as HIV and organ transplant recipients, and is caused by B. henslae and B. quintana. Vectors for these Bartonella species are the cat flea and human body louse, respectively.²

There should be a high suspicion for bacillary angiomatosis in the correct clinical scenario and histopathologic findings can often confirm diagnosis. It is important to differentiate bacillary angiomatosis from Kaposi sarcoma given histopathology similarity.² This can be achieved with concomitant HHV-8 and Warthin-Starry staining. Unfortunately, Bartonella bacilli are not always identified on Warthin-Starry staining. Thus, serologic testing for B. henslae and B. quintana immunoglobulins or serum DNA PCR should also be considered.

First line treatment for bacillary angiomatosis erythromycin dosed at 500mg every six hours.² However, doxycycline 100mg every twelve hours is an appropriate, and sometimes preferred, alternative due to less frequent dosing. Additional treatment options include azithromycin and clarithromycin.² In severe cases of bacillary angiomatosis, combination therapy with doxycycline and gentamicin, doxycycline and rifampin, or azithromycin and gentamicin should be utilized.²

While bacillary angiomatosis is classically associated with immunosuppression, this infection can also occur in immunocompetent patients. Several cases of bacillary angiomatosis arising within second degree burns of immunocompetent patients have been reported.^3,4 Both patients had complete resolution with oral erythromycin.^3,4

References

1. Wolverton SE. Comprehensive Dermatologic Drug Therapy, 4^td Philadelphia. Elsevier.
2. Bolognia JK, Scahher JV, Cerroni L. Dermatology. Philadelphia: Elsevier. 2018
3. Ayse A, Yavuz A, Unai D, Mustafa A, Uyanik MH. A case of bacillary angiomatosis developed at a burn site. Indian J Dermatol VE. 2012;78(1): 121.
4. Karakas M, et al. Bacillary angiomatosis on a region of burned skin in an immunocompetent patient. Br J Dermatol. 2000;143:609-611

June 2020 Case Study

A 41-year-old female presents to clinic with four weeks of “breakouts” on her cheeks. She reports she has been suffering with worsening burning and stinging of the face, which she attributes to her sensitive skin. She has been using waterless moisturizing cream based washes to cleanse nightly, otherwise she denies any new products. Examination reveals the findings shown here.

What is your next best step?

A) Start adapalene 0.1% gel three nights a week, gradually increasing to nightly
B) Order serum antinuclear antibody testing
C) Obtain scraping of skin surface
D) Obtain bacterial culture of intact pustule
E) Order serum ACE levels
F) Start doxycycline 100mg twice daily

Correct Answer: C) Obtain scraping of skin surface

A) Incorrect. This answer implies that the patient is suffering from comedonal acne. While the selection of adapalene 0.1% gel takes into account the patient’s self –reported sensitivity, and there are some scattered hyperpigmented macules concerning for post-inflammatory hyperpigmentation, the lesions not comedonal.

B) Incorrect. This answer implies that the suspected diagnosis is systemic lupus erythematosus. While the malar rash of acute cutaneous lupus can present with centrofacial erythema and have some associated sensitivity, it is generally more confluent and widespread, sparing the nasolabial folds and lacks pustules.

C) Correct. The clinical presentation shown is consistent with a demodex dermatitis, which includes small monomorphic erythematous papulopustules, and gentle scraping of the skin will reveal Demodex mites on KOH prep.

D) Incorrect. Although gram-negative folliculitis can present with eruptive pustules in the facial T-zone in a perinasal distribution, it is usually seen in patients with acne vulgaris receiving long-term antibiotic therapy (which is not the case in this patient).

E) Incorrect. This answer implies a suspected diagnosis of sarcoidosis, which can present with erythema and papules and can be mistaken for rosacea. It would not present with pustules, as in this case.

F) Incorrect. This answer implies a suspected diagnosis of rosacea. Although rosacea can present with papules and pustules superimposed on an erythematous background, there is no appreciable fixed centrofacial erythema, scleral injection, phymatous changes, or facial edema. It is important to note that erythema and telangiectasias can be difficult to discern in the setting of increased background pigmentation, and dermoscopy can be a useful tool to help identify telangiectasias. Also of note, post-inflammatory hyperpigmentation is almost never directly related to rosacea (unless the disease is very chronic and severe or the patient has injured skin inadvertently in an attempt to treat via picking or topical therapies).¹

This month’s case study represents a case of demodex dermatitis, with KOH findings as shown below:

Demodex folliculorum is a vermiform mite that inhabits the pilosebaceous units of the face, most notably the forehead, cheeks, nasolabial folds and nose because of the high density of sebaceous glands in these areas.² Demodex mites have been associated with various inflammatory eruptions including demodectic blepharitis, demodectic folliculitis, demodectic abscess, demodectic alopecia and rosacea-like lesions.³ Demodex mites do not regularly induce illness in healthy hosts aside from eruptions on the face. Severe, problematic eruptions have been associated with patients suffering from myelocytic leukemia, HIV, or diabetes.²

Recent literature review and meta-analysis revealed that patients with rosacea had significantly higher prevalence and degrees of Demodex mite infestation than did control patients, and it has been hypothesized that Demodex mites may play a role in both erythematotelangiectatic rosacea and papulopustular rosacea.⁴ Antiparasitic agents have been used for treatment of rosacea based on the possible role of cutaneous demodicosis with promising results in papulopustular rosacea.⁵

Diagnosis of demodex dermatitis involves skin scraping and KOH prep/microscopy. Treatment options include topical permethrin, sulfur, lindane, benzyl benzoate, or benzoyl peroxide. Oral ivermectin and metronidazole have also been studied as treatment options.³

References

1. Huerth K. Rosacea: Nuances in Clinical Presentation and Treatment. Review of the 2019 Skin of Color Update Lecture by Fran Cook-Bolden, MD. Next Steps in Dermatology. https://nextstepsinderm.com/derm-topics/skin-of-color/rosacea-nuances-in-clinical-presentation-and-treatment/
2. Elston CA, Elston DM. Demodex mites. Clinics in Dermatology. 2014 32, 739-743.
3. James W, Elston J, Treat J. Parasitic Infections, Stings, and Bites. In: Andrews’ Diseases of the Skin. 13^th Elsevier.
4. Chang YS, Huang YC. Role of Demodex Mite Infestation in Rosacea: A Systematic Review and Meta-Analysis. J Am Acad Dermatol. 2017 Sep;77(3):441-447.e6.
5. Stein L, Kircik L, Fowler J et al. Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies. J Drugs Dermatol. 2014;13(3):316-323.

May 2020 Case Study

A 68-year-old female with history of diabetes, hypertension, and rheumatoid arthritis is seen in clinic for a two-week history of oral ulcers. She is experiencing exquisite pain that is impeding her ability to eat and drink. She believes the dose of one of her medications has recently changed but she cannot recall the name of the medication. She is up to date on all age-appropriate cancer screenings and denies fevers, weight loss, or night sweats. On exam, there are erosions and ulcers of the lower mucosal lip with overlying hemorrhagic crust and edema. No other cutaneous findings are noted. Laboratory values reveal pancytopenia with neutropenia.

Based on history and clinical presentation, which of the following medications is most likely the cause of findings?

A.) Furosemide
B.) Metformin
C.) Amlodipine
D.) Methotrexate
E.) Lisinopril

Correct Answer: D.) Lisinopril

Methotrexate is a commonly prescribed therapy by dermatologists as well as rheumatologists and oncologists. It is a folic acid antagonist that competitively inhibits dihydrofolate reductase resulting in decreased folic acid synthesis.¹. Reduced folic acid synthesis subsequently reduces DNA synthesis.¹ Due to the effect on folic acid synthesis, it is important to supplement folic acid while receiving methotrexate therapy. Dosed weekly, methotrexate has been shown to be efficacious in management of psoriasis, atopic dermatitis, and many other dermatologic conditions.² However, simplistic dosing does not preclude from potential side effects.

The most severe side effects include pancytopenia and hepatotoxitcity. Pancytopenia and elevated liver enzymes are often identified early in treatment or in the setting of acute methotrexate toxicity.¹ Conversely, hepatic fibrosis is a rare long-term side effect that should be investigated with liver ultrasound (Fibroscan) or liver biopsy after cumulative dose of 3.0 to 4.5 grams.^1,3 In the event of methotrexate toxicity, as described in this case, clinical findings include pancytopenia, mucocutaneous ulcerations, and transaminitis. If clinical suspicion for toxicity is high, folinic acid should be administered as rescue therapy. Pancytopenia should be monitored and typically reaches its nadir 7 to 10 days after the last dose.⁴ Approach to treatment of mucositis should focus on supportive care.

Prescribers of methotrexate must be aware of several significant drug interactions. Severe myelosuppression can result from concomitant use of other folate antagonists, such as trimethoprim, sulfonamides, and dapsone.^1,2 Additionally, NSAIDs, salicylates, tetracyclines, and loop diuretics can increase the serum concentration of methotrexate, which may result in acute toxicity.¹ Use of alcohol or systemic retinoids while receiving methotrexate therapy can increase risk of hepatic injury or accelerate development of hepatic fibrosis.¹  Ultimately, appropriate counseling on avoidance of particular medications and informing other healthcare providers of methotrexate use are imperative to patient safety.

Adverse reactions of the remaining answer choices do not commonly include mucositis with pancytopenia. Lisinopril is an antihypertensive that has been associated with angioedema and drug-induced subacute cutaneous lupus erythematosus.² Furosemide is a loop diuretic that is associated with drug-induced bullous pemphigoid and pseudoporphyria.² The calcium channel blocker amlodipine is primarily used as an antihypertensive but can also treat Raynaud’s phenomenon. Dermatologic side effects of amlodipine include gingival hyperplasia, drug reaction with eosinophilia and systemic symptoms, and, less commonly, granuloma annulare.² Metformin is an oral antihyperglycemic that is well known for gastrointestinal side effects rather than cutaneous or hematologic side effects.

References

1. Wolverton SE. Comprehensive Dermatologic Drug Therapy, 4^td ed. Philadelphia. Elsevier.
2. Bolognia JL, Schaffer JV, Cerroni L. Dermatology. 4^th ed. Philadelphia. Elsevier Limited.
3. Kalb RE, Strober B, Weinstein G, Lebwohl M. Methotrexate and psoriasis. 2009 National Psoriasis Foundation consensus conference. J Am Acad Dermatol. 2009;60: 824-837.
4. Knoll K, Anzengruber F, Cozzio A, et al. Mucocutaneous ulcerations and pancytopenia due to methotrexate overdose. Case Rep Dermatol. 2016 Sep-Dec; 8(3): 287–293.

April 2020 Case Study

A 54-year-old female with no known medial history presents with recurring crops of pustules on her abdomen and legs (Figure 1). She notes that they will resolve after a few days and does not cause any scarring. Which of the following is most typically associated with this disease?

A.) IgA gammopathy
B.) IgM gammopathy
C.) IgGκ gammopathy
D.) IgGλ gammopathy
E.) IgE gammopathy

Correct Answer: A.) IgA gammopathy

This patient has Sneddon-Wilkinson, or sub-corneal pustular dermatosis (SPD). SPD is a benign disease that causes recurrent crops of sterile, flaccid pustules that are usually asymptomatic but can sometimes be pruritic. They occur most commonly on the flexural surfaces and trunk. The pustules will usually last a few days to weeks before resolving with no scarring. The pathogenesis of SPD is unknown, however there have been associations of SPD with IgA paraproteinemia, neutrophilic diseases such as Sweets and pyoderma gangrenosum, as well as irritable bowel disease and lupus. Most patients can reach complete remission with dapsone but some require other treatments including phototherapy, oral steroids, topical steroids, acitretin, and cyclosporine.

References

1. Watts PJ, Khachemoune A. Subcorneal Pustular Dermatosis: A Review of 30 Years of Progress. Am J Clin Dermatol. 2016;17(6):653-71.

March 2020 Case Study

A 46-year-old man presents with a 6-month history of an asymptomatic rash on his right arm. Prior therapies include topical steroids, emollients, and a 10-day course of prednisone. None of these treatments were effective. Patient denies any history of cutaneous disease, and his medical history is unremarkable. He denies any other systemic symptoms or changes in medications. His clinical presentation and biopsy findings on H&E are shown below. T-cell receptor gene rearrangement study was negative.

Which of the following is the most likely diagnosis?

A.) Purpura annularis telangiectodes of Majocchi
B.) Pemphigus foliaceous
C.) Leukocytoclastic vasculitis
D.) Mycosis fungoides
E.) Angioma serpiginosum

Correct answer: A.) Purpura annularis telangiectodes of Majocchi

Purpura annularis telangiectodes of Majocchi is one of the subtypes of pigmented purpuric dermatosis (PPD). PPD is a benign cutaneous manifestation often characterized by cayenne pepper-like petechiae and purpura with yellow-brown hyperpigmentation. There are no associations with coagulopathies or thrombocytopenia. PPD most commonly presents on the legs but can also appear on the upper extremities and trunk. Purpura annularis telangiectodes of Majocchi is clinically characterized by pinpoint telangiectatic macules in an annular configuration.

Other subtypes of PPD besides purpura annularis telangiectodes of Majocchi include Schamberg disease, lichenoid purpura of Gougerot and Blum, Eczematid-like purpura of Doucas and Kapetanakis, and lichen aureus. Histologically, PPDs are characterized by extravasated erythrocytes in the papillary dermis, perivascular lymphocytic infiltrate, and minimal epidermal change. Perls’ Prussian blue stain is often positive for hemosiderin deposition within the dermis.

Pemphigus foliaceous presents as superficial blisters and crusted erosions. Histologically we would see acantholysis in the upper epidermis, and DIF would demonstrate IgG and C3 deposition within the epidermis. Leukocytoclastic vasculitis is characterized by palpable purpura, and common pathologic features include perivascular neutrophilic infiltrate with leukocytoclasia, fibrinoid necrosis, and extravasation of red blood cells. PPDs are considered a T-cell dyscrasia by some, and it can present similarly to poikilodermatous mycosis fungoides. However, we would expect the T-cell receptor gene rearrangement to be positive. Angioma serpiginosum is a benign vascular malformation most common in young females and usually presents as grouped red macules and telangiectasias in a serpiginous or linear pattern.

References

1. Kim DH, Seo SH, Ahn HH, Kye YC, Choi JE. Characteristics and Clinical Manifestations of Pigmented Purpuric Dermatosis. Ann Dermatol. 2015 Aug;27(4):404-10.
2. Plachouri KM, Florou V, Georgiou S. Therapeutic strategies for pigmented purpuric dermatoses: a systematic literature review. J Dermatolog Treat. 2019 Mar;30(2):105-109.
3. Bolognia, Jean., Schaffer, Julie V., Cerroni, Lorenzo, 4th ed. Dermatology. Elsevier Limited, 2018. Print.

February 2020 Case Study

77 year old woman with no personal or family history of skin cancer presented with a lesion on her R heel that she noticed 2 months prior. She had not noticed any growth of the lesion and it was not tender. On physical exam she had a 1.2 x 0.9 cm dark brown/black plaque with hyperkeratosis on the R plantar heel with no lymphadenopathy (Image 1).  On pathology, there was an asymmetric proliferation of atypical melanocytes disposed as nests and single cells present within the epidermis of volar skin and a dermal component identified to 1.2 mm with ulceration. She underwent wide local excision and sentinel lymph node biopsy, which was positive for two lymph nodes with microscopic invasion.

Based on the following information: What is the patient’s pathological tumor stage and overall AJCC8 stage?

A.) T Stage pT2a, AJCC8 Stage IIb
B.) T Stage pT2b, AJCC8 Stage IIIb
C.) T Stage pT2a, AJCC8 Stage IIIb
D.) T Stage pT2b, AJCC8 Stage IIIa
E.) T Stage pT3b, AJCC8 Stage IIIb

Correct answer: B.) T Stage pT2b, AJCC* Stage IIIb

Based on AJCC8 staging criteria, the pathologic tumor stage would be considered pT2b because the thickness is between 1.0-2.0 mm with ulceration. Answers A and C are incorrect because although the thickness is between 1.0mm and 2.0 mm there is ulceration present making pT2b the correct answer. Answer E is incorrect because the thickness is not >2.0 mm- 4.0 mm, making pT3b incorrect. The nodal disease stage would be N2a because the sentinel lymph node biopsy was positive for two microscopic lymph nodes.  There were not lymph nodes detected clinically so the nodal disease stage would not be N2b. Based on the tumor stage and the nodal stage the AJCC8 stage would be IIIb as shown in the table below. Answer D is not correct because the Stage is IIIb, not IIIa.

According to NCCN guidelines, sentinel lymph node biopsy is generally not recommended for < 0.8 mm.  For tumors with a thickness of 0.8-1.0 mm sentinel lymph node biopsy should be discussed and considered. High risk features to consider for these patients include ulceration, mitoses, and lymphovascular invasion. Sentinel lymph node biopsy should also be discussed and offered to patients with a thickness of > 1.0 mm.

References

1. Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: Evidence‐based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA: A Cancer Journal for Clinicians. 2017;67(6):472-492. doi:10.3322/caac.21409
2.  Coit DG, Thompson JA, Algazi A, et al. Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN. 2016;14(4):450-473.

January 2020 Case Study

The patient is a 40 year old female who presents for evaluation of persistent eyelid dermatitis. The eyelid dermatitis has been present for 1 year and has never completely resolved while using topical corticosteroids or calcineurin inhibitors. She describes the rash as itchy but not painful and has not noticed any lesions in other areas. Currently she uses “all natural” personal and cosmetic products including a “fragrance-free” oil on the face. The patient is diagnosed with allergic contact dermatitis of unspecified trigger and patch testing is performed to the North American Standard Tray and Cosmetic Tray (Image 1). A positive patch reaction is noted on the 96 hour read (Image 2). Which of the following allergen did this patient likely react to?

A.) Dimethylol dihydroxyethylene-urea resin
B.) Lanolin
C.) Paraphenylenediamine
D.)Melaleuca alternifolia
E.) Fragrance mix (cinnamic alcohol, cinnamic aldehyde, hydroxycitronellal, amylcinnamaldehyde, gerianiol, eugenol, isoeugenol, oakmoss)

Correct answer: D. Melaleuca alternifolia

Allergic contact dermatitis (ACD) is an inflammatory skin disorder characterized by delayed type IV hypersensitivity. It has a prevalence of approximately 20% and patients with atopic dermatitis may have an increased risk of developing contact dermatitis.¹ The eyelids and periorbital area are common locations for ACD and are frequently due to allergens found in cosmetic and personal products including fragrances, formaldehyde-related preservatives, methylisothiazolinone, and cocamidopropyl betaine.¹

Patch testing is the best tool to confirm a diagnosis of ACD.² It involves applying allergens on a patch to the back or upper outer arm of the patient. The patches are removed after 48 hours where an initial read is taken and then a final read is completed at day 4 or day 5. A positive reaction will reveal an erythematous papule or vesicle with edema.²

Melaleuca alternifolia leaf oil is commonly referred to as tea tree oil and is becoming a frequent cause of ACD. M. alternifolia is a part of the North American Contact Dermatitis Group screening patch tray and has a prevalence of 3.5% of positive reactions.³ Clinically, patients have a localized dermatitis depending on where the product is topically applied. The periorbital area is a common location for cosmetic products.³ Patients may present with erythematous patches to eczematous plaques to bullous or erythema multiforme-like reaction.⁴ When there is a high suspicion of M. alterifolia as a cause of ACD, patients should be patch tested to the 5% formulation in petrolatum along with the patient’s personal products if possible.⁴ Allergy avoidance and providing the patient with a list of safe products is a necessary part of treatment.

Other answer choices:

Formaldehyde resins like, dimethylol dihydroxyethylene-urea, are commonly used in fabric production to make them wrinkle or water resistant.⁵ Lanolin contains sterols or fatty acids and is common in many personal and cosmetic topical lotions and creams.⁵ Paraphenylenediamine (PPD) is used in hair dye and frequently causes ACD of the scalp, eyelids, ears, forehead, and neck.⁵ There are 2 fragrance mixes found in the North American Contact Dermatitis Group screening tray which covers many fragrances found in perfumes/colognes, oils, cosmetic, personal and household products.⁵

References

1. Nassau, S., Fonacier, L. F. (2020). Allergic contact dermatitis. Med Clin N Am, 104, 61-76.
2. James, W., Elston, D., Treat, J., Neuhaus, I., & Andrews, G. (2020). In Edinburgh (Ed.), Andrews’ diseases of the skin : Clinical dermatology (Thirteenth edition ed.) Elsevier.
3. de Groot, A. C., & Schmidt, E. (2016). Tea tree oil: Contact allergy and chemical composition. Contact Dermatitis, 75(3), 129-143. doi:10.1111/cod.12591 [doi]
4. Larson, D., & Jacob, S. E. (2012). Tea tree oil. Dermatitis, 23(1) Retrieved from https://journals.lww.com/dermatitis/Fulltext/2012/01000/Tea_Tree_Oil.10.aspx
5. Allergen information. (2020). Information posted to https://www.contactderm.org/public-and-patients/allergen-information