ABOUT VGRD

Founded in 2000, Virtual Grand Rounds in Dermatology (VGRD) is a gathering place for dermatologists the world over to meet with one another and share interesting and/or challenging patients. In addition, we welcome all other health care practitioners with an interest in cutaneous disorders.  One may want to ask a question about diagnosis or therapy, present an interesting clinical photo or post a photomicrograph. We are a group of clinical and academic dermatologists who believe that web-based teledermatology can be both personally and professionally enriching.

Digital photography makes it possible to post clinical and microscopic images with ease. There are a dizzying number of cameras to choose from. The site creators will help you with advice here if you want.  In the past few years, smart phones have improved to the point where their images are more than acceptable.

Even if one lives in a city with a major medical center it is often difficult to get one's patients to Grand Rounds. And if one does, the turnout and discussion may be disappointing. VGRD is always available. You can post a message at 6:00 p.m. in Boston, Henry Foong may see it at 6:00 a.m. in Ipoh, Malaysia as he sits down at his home computer. Often, you will have received a few suggestions or comments when you log on the next morning.

VGRD has been a virtual consultative and collegial community for over 15 years. John Halle, the 16th Century English physician/poet, penned these perceptive words about the consultation in a long forgotten tract:

    When thou arte callde at anye time,

    A patient to see:

    And dost perceave the cure to grate,

    And ponderous for thee:

    See that thou laye disdeyne aside,

    And pryde of thyne own skyll:

    And think no shame counsell to take,

    But rather wyth good wyll.

    Get one or two of experte men,

    To helpe thee in that neede;

    To make them partakers wyth thee

    In that work to procede....

Halle's words guide us as we gather 500 years later in a consultative community the likes of which he probably could not have fathomed. So, let us "laye disdeyne aside,/ And pryde of [our] own skyll:/ And think no shame counsell to take,/ But rather wyth good wyll" join us in this global community of peers to help our patients and educate each other and ourselves.

Painful Finger Tips Secondary to Opdivo

The patient is a 65-year-old woman with metastatic lung cancer who presents for evaluation of painful fingertips.  She has also had marked axillary pruritus which she handles with Lotrisone spray. 

Her medications include metformin, two types of insulin, metoprolol, Lipitor, Lexapro, and irbesartan.  Recently, she has been started on Opdivo (nivolumab) every two weeks.  Within a few months of starting Opdivo, she developed intense axillary pruritus, and a month or so later, intensively painful fissuring of the fingertips.  Each treatment of Opdivo re-exacerbates the fingertip problem, which is unbearable. Her cancer has gone into remission and she feels well otherwise.  She especially enjoys her grandkids.

Her oncologist put her on prednisone 20 mg q.i.d. for the fingertip eczema.  Because of the patient's diabetes, her fasting blood sugars while on prednisone have gone up over 500 mg%. 

EXAMINATION:  The examination shows erosions on a few of the fingertips without erythema.  Her feet and axillae are normal.  

Clinical Photos:

We did a literature search and there are a few early reports of dermatitis with Opdivo but they do noot not affect the hands.  It may be too early to say; but given the literature on painful hands and feet related to cancer therapies this is probably a significant reaction.  

PLAN:  I would try to keep this simple and avoid the prednisone.  Start with wet soak for 20 minutes in warm water, followed by clobetasol ointment, followed by gloves (a modified Soak and Smear protocol).  We will see how she does with this.  I have the patient's permission to post her case on this site where we may get ideas and/or be of help to others with a similar problem.   There is a reference to preventing Hand Foot reactions with chemotherapy.  It seems that Celebrex (celecoxib) may be the best option. Note: Celecoxib has been reported to be associated with an increased incidence of heart attack and stroke.  It's use should not be cavalier.

References:.

1. Survey of cutaneous adverse reactions to targeted cancer therapies: value of dermatological advice. Damiani G OncoSkin working group. G Ital Dermatol Venereol. 2018 May 11. Abstract: From June to October 2012, 25 patients with cutaneous adverse reactions linked to targeted therapies were included in the study. The main prescribed drugs were cetuximab (52%) and erlotinib (20%) and the most common reactions were folliculitis/pustules (40%) and rash/erythema (40%). Hand-foot reaction syndrome was present in 8% of patients. A total of 30% of patients treated for a cutaneous reaction underwent a consultation by a dermatologist. In these patients the rate of oncologic therapy continuation without regimen modifications was higher (100%), while it was progressively lower in patients treated by oncologists (71%) or without any specific treatment (60%). Adverse reaction should be recognized by both dermatologists and oncologists and a multidisciplinary approach is mandatory.

2. Prevention strategies for chemotherapy-induced hand-foot syndrome: a systematic review and meta-analysis of prospective randomised trials.

Macedo LT, et.al. Support Care Cancer. 2014 Jun;22(6):1585-93.

Abstract

Amongst 295 studies identified, only ten met the inclusion criteria. Celecoxib prevented both moderate to severe (odds ratio [OR] 0.39, 95 % confidence interval [CI] 0.20-0.73, P = 0.003) and all-grade HFS (OR 0.47, 95 % CI 0.29-0.78, P = 0.003), whereas pyridoxine and topical urea/lactic acid formulations failed to prove efficacy. There were no proven benefits in mild HFS. The use of topical antiperspirant has not been shown to improve results, according to a single trial.

Generalized Pustular Eruption in a 27 yo woman

The patient is a 27 yo woman with a 2 week history of an evolving, wide-spread eruption.  The initial lesions were on the popliteal fossae.  These were described as erythematous areas studded with pustules.  Over a week or two these generalized.  She has a history of mild psoriasis (scalp and elbows) for over a decade.  About three months ago she was started on bupropion 75 mg a day for anxiety and restlessness.  This was increased to 150 mg per day ~ 2 week before the onset of the dermatitis.  The patient has moderate cognitive impairment and Type 2 diabetes.  Here other medications include thyroid supplementation, metformin and insulin.  In the days since her initial office visit, the eruption has become more extensive and is taking on an erythrodermic appearance.  She was admitted to hospital two days after her office appointment.               

O/E:  When seen on May 7, 2018, she had a widespread eruption on arms, legs and torso,  The lesions were large arcuate patches with pustules at the periphery.  She was experiencing considerable pain.

Clinical Images:

 Pathology: (courtesy of DR. Erin Tababa, Fellow in Dermatology, Boston University)  

The biopsy shows prominent, relatively large, subcorneal pustules that are filled with a dense exudate of acute inflammatory. The neutrophils extended into the underlying epidermis, which has evidence of mild spongiosis. The papillary dermis is slightly oedematous, and there is a moderately dense perivascular inflammatory infiltrate with a predominance of neutrophils, although no eosinophils are noted.

Lab:

WBC: 29,000

Differential:  Shift to left

Eosinophils: normal
G6PD Normal

Chemistries normal.

Wound Culture: Pending

Dx:  We are initially considering subcorneal pustulr dermatosis, but with more history, especially considering the recent prescription of bupropion a drug-induced annular pustular psoriasis evolving into pustular and exanthematous psoriasis seemed more accurate.  Histopathology supported that.  Similar reactions have been reported to bupropion.  Our patient had been on the bupropion for over a month when this began which is longer than the patients in the case report below.  Reference 2 is a similar patient with a long latent period between initiation of drug and development of GPP.

Follow-up in hospital.  The eruption continued to evolve. It became more exanthematous and desquamative. These pictures were sent us by her mother.

Plan: 

Cyclosporin 3 – 4 mg per kg per day in divided doses

Wet dressings followed by triamcinolone 0.1% ointment bid – tid

Adjunctive secukinumab has been reported to be effective.

Follow-up:
Patient is doing very well.  These photos were taken 5 days after starting cyclosporine 100 gm q.i.d.  Her dose was dropped to 100 mg t.i.d.  She also was treated with wet dressings and triamcinalone ointment 0.1% (although the hospital only gave her 15 mg tubes, so she could not cover most ot the lesions. 

References:

1. Generalized pustular and erythrodermic psoriasis associated with bupropion treatment. Cox NH, Gordon PM, Dodd H. Br J Dermatol. 2002 Jun;146(6):1061-3.

Abstract: Severe drug eruptions may cause diagnostic and therapeutic difficulty when they mimic or provoke endogenous patterns of dermatosis. We report three patients with known psoriasis in whom use of bupropion (Zyban), prescribed to assist with cessation of smoking, led to severe pustular or erythrodermic exacerbation of psoriasis within 3-5 weeks. All patients were systemically unwell and required hospitalization to control the disease flare.

2. A diagnostic challenge: acute generalized exanthematous

pustulosis or pustular psoriasis due to terbinafine

L. Duckworth et.al. Clin Exp Dermatol. 2012 Jan;37(1):24-7

Abstract:  A 72-year-old man developed a generalized erythematous pustular eruption 11 weeks after commencing terbinafine. Clinically and histologically, the appearance was that of acute generalized exanthematous pustulosis (AGEP), and the disease was managed with topical preparations. Initial improvement was marred by relapse of acute pustulosis, now more in keeping with terbinafine-induced pustular psoriasis (PP),which was successfully treated with acitretin. This case highlights the difficulty of differentiating between AGEP and PP.

3. Acute generalized exanthematous pustulosis mimicking toxic epidermal necrolysis in patients with psoriasis: a coincidence?

Worsnop F, et. a. Clin Exp Dermatol. 2015 Aug;40(6):688-9

.

An Infant Girl from Rwanda with a Congenital Dermatosis

presented by Caitlun Stiglmeier, M.D.

I was hoping to have some input on this case.The patient is an 11 month old female infant born via spontaneous vaginal delivery, to a G1P1 mom (young, but not sure of mothers age). No reported maternal history of perinatal infections. TORCH screening performed on the child during this admission is negative. The child has bilateral retinal detachment, but her hearing is retained. She has gross developmental delay, and the rash you see in the photos started after birth on the R forearm, and has migrated since to all areas of the body, including the chest, back, yo the upper and lower extremities, and scalp. Her mother states the rash begins as blisters (second photo), which then open (no drainage noted per mom) and leave areas of hypopigmentation (third photo) and finally hyper-pigmentation (first photo).

The child does not seem bothered by this rash, it is not pruritic, and she does not have any fevers. Despite negative TORCH screening, I'm still thinking along the lines of a congenital-type of disease. Your thoughts would be greatly appreciated!

Dr. Yoon Cohen wrote:
The clinical description and the images seems to go with incontinentia pigmenti in this her 11 month infant girl.
For management, the skin changes of IP usually do not requires any specific treatment other than wound care for blisters to prevent secondary skin infection. The baseline eye exam and close follow up by an ophthalmologist will be important, especially with her retinal detachment history. Neurological evaluation should be done for potential seizures, encephalopathy and ischemic stroke. Dental evaluation is recommended after teeth erupt for pegged or missing teeth. Other ectodermal abnormalities can be seen as alopecia and nail dystrophy.  In countries with more resources, this infant would benefit from being seen at a center where the pediatric dermatologists have more experienc with genodermatoses.

References:
1. I.P. NORD site.
2. I.P. GARG (NIH Genetic and Rare Diseases information site)
3. I.P. World Community  (some parts in French)

FADES

The patient is a 17 yo boy with a 10 year history of asymptomatic hyperkeratosis of both elbows.  His knees are normal.  He has no personal history of atopy and both he and his mother deny that he rubs or scratches the area.  He's embarrassed by this and avoids sports as a result.  He is moderately obese and does not exercise or do sports.

O/E:  Symmetrical hyperkeratosis of both elbows.  Knees perfectly normal as is the remainder of his cutaneous exam.  He is moderately overweight.

Clinical Images:

Diagnosis: Asymptomatic Frictional Hyperkeratosis of the Elbows

Comment:  I suppose we all see this entity on frictional sites, but rarely name it.  The patient denies rubbing or scratching the area but was observed to lean on his elbows.  A similar problem has been reported (see reference  1. below).  I recommended starting with 5% Keralyt gel twice daily and may add tretinoic acid.  I propose that this type of hyperkeratosis can follow pressure on bony prominences, such as is seen on the foreheads of devout Muslims who pray 5 times a day (2).  Prayer marks in Muslims appear to be more common in diabetics (3).  The patient described in this VGRD  post could well have the metabolic syndrome.  I wonder if this might be important. I'd appreciate your  thoughts. 

Reference:

1. Frictional asymptomatic darkening of the extensor surfaces.

Krishnamurthy S, Sigdel S, Brodell RT. Cutis. 2005 Jun;75(6):349-55.

Abstract: Frictional asymptomatic darkening of the extensor surfaces (FADES), also known as hyperkeratosis of the elbows and knees, is commonly seen by dermatologists but has never been well characterized. Patients present with uniform, asymptomatic, brown darkening over the extensor surfaces of the elbows and knees with minimal scaling. Both frictional stress and family history may play a role in the pathogenesis of this condition. The results of cutaneous biopsy specimens typically reveal hyperkeratosis, acanthosis, and mild papillomatosis with minimal inflammation. Keratolytic agents such as lactic acid and urea cream along with avoiding frictional stress can be effective in the management of this condition. We describe a series of cases of FADES and its etiology and management options.

Comment in: Frictional asymptomatic darkening of the extensor surfaces. [Cutis. 2007]

2. Prayer marks. Abanmi AA et. al. Int J Dermatol. 2002 Jul;41(7):411-4.

Prayer marks (PMs) are asymptomatic, chronic skin changes that consist mainly of thickening, lichenification, and hyperpigmentation, and develop over a long period of time as a consequence of repeated, extended pressure on bony prominences during prayer. PubMed.

3. Prayer Marks in Immigrants from Bangladesh with Diabetes Who Live in Greece.  Papadakis G, et. al. J Immigr Minor Health. 2016 Feb;18(1):274-6. PubMed.

Demodeciasis: One off

The patient is an 86 yo man was tarted on imbruvica for a lymphoma in August of 2017.  Around a month later he developed a facial eruption that had the appearance of rosacea.  As it was mild, it was not treated.  The eruption has worsened over the past few months.

O/E  There are erythematous papules and pustule on the right malar eminence and erythema and mild swelling of the nose.  The left malar eminence and the remainder of the  head and neck are normal.

Clinical Photos:

Lab:  A scraping from two papules revealed numerous (apparently happy) demodex mites.

Diagnosis:  Demodeciasis, most likely as a side-effect of imbruvica.  This has not been reported in the literature at present, but I suspect it will be soon.

Treatment was initiated with Sklice (topical ivermectin).  If this is not effective, he will be offered oral ivermection.  The latter may have been a better strategy.

Follow-up 10 days after starting ivermectin Solution (Sklice);  ~ 50% better.

 

Reference:

1. Parmar S, Patel K, Pinilla-Ibarz J.

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. P T. 2014 Jul;39(7):483-519.  Free Full Text.

2. Patrizi A1, Bianchi F, Neri I.  Rosaceiform eruption induced by erlotinib. Dermatol Ther. 2008 Oct. Suppl 2:S43-5.

Abstract:

Adverse events with anti-epidermal growth factor receptor therapy mainly involve the skin. The most common cutaneous adverse event is an acneiform eruption, which occurs in more than 50% of cases. The aim of this paper is to report the case of rosaceiwform eruption induced by erlotinib in an 81-year-old-man and to discuss the pathogeneic role of Demodex folliculorum mites, found in the present patient, using skin scraping.

Granulomas in 62 year-old fisherman

Presented by Dr. Henry Foong
Ipoh, Malaysia

A 62 yr old man presented with 4 weeks history of pruritic papular lesions on the thighs bilaterally which then spread to the legs. The pruritus was intermittent and he felt feverish at times. No history of trauma. He is a retired fisherman and lives  in Teluk Intan about 60 km south of Ipoh, Malaysia.

O/E: showed multiple indurated erythematous papules, non-tender distributed symmetrically over the inner thighs and legs. Superficial erosions and ulcerations were noted on the affected areas. There was no crepitus.

The referring physician suspected elephantiasis. The patient is on oral antibiotics ( metronidazole and unasyn) and albendazole.  At one time he was on DEC (diethylcarbamazine)  but it was withheld because of side effects.

Lab: Blood counts showed normal TWBC with 7% eosinophils.  The physician did a colonoscopy last month and biopsy suggested underlying parasitic colon infection.

Culture of the skin lesions - Clostridium perfrigens.

A skin biopsy was performed on the skin papules on the thigh.

Pathology: Skin biopsy showed epidermis with marked spongiosis. the dermis show cluster and scattered granulomas with abundant surrounding neutrophils and plasma cells.  There is a huge collection neutrophils with necrotic material. There are multinucleate gaints granulomas. The inflammatory cells involved the subcutaneous fat.

Clinical and Pathological Images:

Impression:  Sporotrichosis?

Questions: What are your thoughts? What further studies would you consider.