Wednesday, June 24, 2020

A Case for Diagnosis

Presented by  Dr. Henry Foong, Ipoh, Malaysia

The patient, a Chinese woman in her 30s, presented with sudden flare of her skin eruptions on the legs past 2 weeks.  She had been having multiple erythematous plaques on the abdominal wall and legs since March 2020 and had tried various topical creams and oral supplements.  As it happened during lockdown she had tried online medications and topical creams.  The lesions on the abdominal wall improved but suddenly those on the legs flared up with painful pustules.  She denied any fever.  Apparently she was on oral methotrexate previously for psoriasis but according to her, MTX did not help her much.  

Clinical:
Her vital signs are stable. No signs of dehydration. 
Extensive erythematous plaques on the lower limbs.  Edges well demarcated. scaly surface. some of the larger lesions had a central smooth glazed appearance surrounded by crops of tiny superficial pustules.  Post inflammatory hyperpigmentation were prominent on the anterior abdominal wall.
No nail changes were noted.  Joints were normal.
Images:

Diagnosis:
Generalised pustular psoriasis of von Zumbusch

Note:  We presented a similar patient two years ago.

I suspect she may have taken oral corticosteroids and when she stopped the oral medications, the lesions flare up.  A skin biopsy was done.  This may be useful to exclude AGEP.  Blood counts/biochem/swab culture including serum calcium were done and pending.   
In the meantime, she is on IV fluids, IV antibiotics, topical moisturisers, KMNO4 soaks and topical corticosteroids.

Q1.  Would IV hydrocortisone be useful in this patient or avoided at all costs?
Q2.   Is it worthwhile to try MTX weekly dose again?  Cyclosporin? Oral acetretin would not be practical for a woman of child bearing age group. 
Q3.  Biologics may have a role.  Anti IL-36 recently was found to be useful in pustular psoriasis but this drug is not available yet.  Which other biologics would be useful? Risankizumab?

Thank you for your thoughts on this patient.

Monday, June 22, 2020

Angiokeratoma of the Vulva


The patient is a 32-year-old woman who was seen today for lesions on the vulvae.  She saw a gynecologist because one of them was bleeding and he told her that they were cherry angiomas and that she should see a dermatologist. 
  
EXAMINATION:  The examination shows a pleasant, moderately obese woman.  On the vulva, she has scores of purple papules measuring 1-2 mm in diameter. 
    

Photo
IMPRESSION:  These are angiokeratomas of the vulvae.  They are different from cherry angiomas.  There was one lesion that has been occasionally bleeding although today is quiescent.  I could remove that with ED&C when it becomes more active. 

Reference:
1. Angiokeratoma of the Vulva
[Article in English, Portuguese]
Leticia Fogagnolo  1 , et. al 
An Bras Dermatol Mar-Apr 2011;86(2):333-5. PMID: 21603817
Abstract: Angiokeratomas are benign tumors characterized by ectasia of blood vessels in the papillary dermis associated with acanthosis and hyperkeratosis of the epidermis. Dermatological examination of angiokeratomas of Fordyce is characterized by papular keratotic lesions of erythematous-violet color. They are more common in the scrotum, and vulvar involvement is rarely reported. Histopathology is particularly important to distinguish them from other benign and malignant tumors. The article reports the case of a middle-aged black woman with a history of chronic constipation, varicose veins of the lower limbs and cesarean section performed 20 years ago who had had multiple vulvar angiokeratomas for three months.



Friday, June 12, 2020

She’s Not Handling This Well


The patient is a 65 year-old woman with a two-month history of hand dermatitis.  She has had no new medications in a year and has been laid off from a job in sales due to Covid 19.  After 25 years, she’s had to sell her house and is moving into an apartment in three days time.  Holding up her hands up in front of her, without irony, she said, “I’m not handling this situation well.”


Clinical Exam: The palms of both hands are dry with marked scale plates.  The dorsae of the hands are normal.  There are no other cutaneous findings.  In the photo above, there is a suggestion of Dennie-Morgan Lines.  Her feet are normal.


Discussion:  In the differential diagnosis I considered traumiterative hand dermatitis, psoriasis, contact dermatitis, tinea (KOH was negative).
But I keep wondering about that phrase in English, “She can’t handle it.”  Why is that aphorism there?  Did the Ancients know something we’ve forgotten?

She will be treated with clobetasol ointment employed with a “Soak and Smear” protocol.  If she does not clear by a few weeks after her move, biopsy, patch testing, and a medical workup will be pursued, but she has other things on her plate just now.

Monday, May 25, 2020

~ 4000 Times the Price of Gold


I made a house call on an 90 year old patient yesterday.  He lives with his wife in an idyllic house surrounded by vernal gardens and a wetland preserve.
 
The patient was presented on VGRD in 2014 with a desmoplastic melanoma of the scalp that measured > 7.5 mm thick.  Since that time, he has done reasonably well.  A metastatic lymph node was excised from the r. preauricular area ~ 4 years ago.  He was doing well until early May, 2020 when he developed right upper quadrant pain.  The ER work-up suggested non-ST-elevation myocardial infarction (NSTEMI) and he was admitted to a local hospital.  There, elevated LFTs were noted and scans confirmed presence of multiple liver masses (largest being 3 cm diameter) and enlarged mesenteric lymph nodes (largest 3.6  cm diameter). A supraclavicular l.n. was biopsied that showed metastatic melanoma.
Significant co-morbidities include recent osteomyelitis (left foot) for which he is currently on oral medication (doxycycline), HTN, gout and the recent NSTEMI, and ischemic cardiomyopathy with a depressed EF (25-30%).
Medications: metoprolol, lisinopril, Plavix, Lipitor, allopurinol, and ASA

He is a high functioning nonagenarian who lives independently with his wife and until the past few months was doing well.

His oncologist is recommending Ketruda (pembrolizumab).  When I spoke with the patient a few days ago he told me that the oncologist said Ketruda was well-tolerated, but when I checked the oncologist’s notes the recorded discussion of side-effects ran 12 lines on the office note. 
Yesterday, the patient gave me a printout he independently made.  After he and his wife read it, and he now has doubts.  His quality of life is good, he enjoys his home, meals, and an occasional dram of Johnny Walker Black… he spoke of quality of life over a few extra months.  He’s done all he wanted to do in life.
We plan to sit down this week in my office and have a more formal discussion.

His metastatic lesions were discovered incidentally as a result of hospitalization for his NSTEMI.  Is this a good sign that pembro will be helpful, or at this time do the risks outweigh the benefits?  When the randomized studies were done with pembro, were nonagenarians with cardiomyopathy or significant co-morbidities excluded?
Your thoughts will be appreciated. 

Postscript: A week after I saw him, he had a PET scan.  The next day, he developed profound weakness. He took to his bed.  Stopped eating and drinking.  He became stuporous and died two days after the scan attended to by his loving wife and a caring nurse.  The day after he died, his oncologist called with the PET scan results.  His liver was entirely replaced with tumor.  He told her that Ketruda was not indicated in such a situation.  He lived reasonably well until two weeks before he died.

Reference
1. Few people actually benefit from ‘breakthrough’ cancer immunotherap
y
By
Nathan Gay and Vinay Prasad. March 8, 2017. Stat Topics.  [We will try to see if the authors still believe this]

2. Alyson HaslamVinay Prasad  Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs. JAMA Netw. 2019 May 3;2(5):e192535.  Free Full Text at PMC.
3. Madhuri Bhandaru, Anand Rotte  Monoclonal Antibodies for the Treatment of Melanoma: Present and Future Strategies. Methods Mol Biol. 2019;1904:83-108.  A Review

 




Sunday, May 10, 2020

Hairband Alopecia in a Covid Carer

May 8, 2020
Dr. Z. is a 30 year-old ophthalmology resident called to duty on the Covid ward of a large East Coast metropolitan hospital where over a 1000 Covid patients had been treated to date.  In this age of telemedicine, she wrote me the following:
“Our community was hit hard by this pandemic, and we continue to help out on the Covid floors. It’s been a scary and yet rewarding experience!
I want to ask your opinion regarding a dermatology question! Last night I noticed a small patch of hair missing. I think it was in the area where I was wearing a tight hairband while in the hospital about 3 weeks ago. I had the hair band on for four days. It was so tight that the area would hurt when I took it off at night after a long shift. I just didn’t want any hair in front of face on Covid ward. I was wondering if there is anything I need to do about it? Or just wait for it to grow out. The scalp area looks a little red, here are two photos.”















While this appears to “pressure alopecia,” I offered to run Dr. Z.’s anamnesis by a colleague with a special interests in disorders of hair.  How we practice now is different from a few months back.  We will be seeing new variations on a theme such as perhaps, Hairband Pressure Alopecia.

References:
1. Sano DT, et. al. Headband pressure alopecia: clinical, dermoscopy, and histopathology findings in four patients. Int J Dermatol. 2018. Feb;57(2):237-239

2. Iwai T, et. al. Temporary alopecia caused by pressure from a headband used to secure a reference frame to the head during navigational surgery. Br J Oral Maxillofac Surg. 2009 Oct;47(7):573-4. 

We consulted with a dermatologist nationally recognized specialist interest hair disorders.  She responded “I do not have much experience with pressure induced alopecia, likely because the etiology is apparent and it regrows in most cases. The photos do suggest pressure alopecia, although there is a differential for patchy alopecia including alopecia areata and tinea capitis. As you know, the current theory is that it is ischemic in nature. I wonder how tight the headband was! Her area of loss is small and it looks rather non-inflammatory, so one would think prognosis for regrowth would be good. It can take a couple of months to see new sprouting hair shafts. Scarring can occur if the insult is severe or prolonged – this can sometimes result in ulceration which is not present."
 

Monday, April 27, 2020

Hailey-Hailey Disease masquerading as Recurrent "Tinea cruris"

Dr Henry Foong
Ipoh, Malaysia

The patient, in his 50s, presented with a 10-year history of  recurrent pruritic skin eruptions on the groins and axilla. He was treated by his GPs as well as a urologist for "infected tinea cruris" with oral antifungals, IV antibiotics, topical steroids, topical antifungals but the treatments did not help. For the past 3 months, the lesions have worsened. He had no fever or other constitutional symptoms.  He had no history of diabetes. His father apparently had similar skin lesions. 

Examination showed erythematous plaques with vesiculation and superficial fissures and erosions on the groins extending to the scrotum, inner thighs and intergluteal cleft. The lesions appeared to be bilateral, symmetrical, hyperpigmented and well demarcated. Similar lesions were noted on the axilla. There were no bulla or purpura. There was no oral or nail lesions. KOH exam for hyphae was negative on 3 occasions.

Initial provisional diagnosis was that of tinea incognito but KOH exam was repeatedly negative.  Hailey-Hailey disease a.k.a. familial benign chronic pemphigus was considered in the differential diagnosis.  





A skin biopsy with DIF was done.  H&E shows focal and central lesion of suprabasal and intraepithelial clefts containing basophilic cells with large nuclei and a paranuclear halo.  There is a presence of basal keratinocytes attached to basement membrane forming a characteristic tombstone, or ‘‘dilapidated brick wall’’ appearance. Corps ronda cells are not prominent. The stratum corneum shows parakeratosis and hyperkeratosis with focal neutrophilic infiltrates.  The upper dermis shows perivascular infiltrate of lymphocytes, histiocytes and eosinophils.
Immunofluorescence studies show IgG, IgA , IgM, C3 were negative.

Interpretation: Acantholytic epithelial lesion consistent with familial benign pemphigus.



The management of this patient may be challenging.  General measures such as wearing lightweight and loose clothing would be helpful.  Avoiding friction on the affected areas, use of mild antiseptic solutions  and reduction in sweating are also advisable. In terms of specific treatment, we plan to start with topical calcineurin inhibitors and oral antibiotics such as doxycycline 100mg bd. Other possible options include low dose naltrexone, methotrexate, dapsone, azathioprine, etanercept, apremilast, botox and laser treatment.  Low dose naltrexone appeared to be very effective in some of the cases but may have variable responses according to the dose.

References
1. Imene Ben Lagha, Kurt Ashack, Amor Khachemoune.  Hailey Disease: An Update Review with a Focus on Treatment Data.American Journal of Clinical Dermatology Oct 2019.  https://doi.org/10.1007/s40257-019-00477-z
2. Hohl D. Darier disease and Hailey–Hailey disease. In: Bolognia J, Jorizzo J, Schaffer J, editors. Philadelphia: Elsevier Inc; 2012. p. 887–97.
3. Severine Cao, Evelyn Lilly, Steven T. Chen. Variable Response to Naltrexone in Patients With Hailey-Hailey Disease. JAMA Dermatol. 2018 Mar; 154(3): 362–363. 

Monday, April 06, 2020

68 year-old woman with subcutaneous lesions

Presented by Dr. A.R. Pito, Retired, Volunteer Dermatologist
Queens Memorial Medical Center
New York, New York

This 68-year-old woman presented for evaluation of painful lesions under the skin that have been present for 3-4 months. She has a history of psoriasis, which is in remission, fibromyalgia, hypertension.  There is no personal history of malignancy.  No exotic travel.  She had smoked over two ppd for decades.

EXAMINATION: The examination shows a woman who appears slightly older than her stated age. She has 6-8 freely movable subcutaneous smooth-surfaced lesions on the back, posterior nuchal area, and the upper chest. The largest is ~ 5 mm in diameter. The remainder of the exam plus breast palpation was unremarkable.  No adenopathy appreciated.


INITIAL MPRESSION: Subcutaneous skin lesions, present for only a short period of time. Etiology is unclear.

PLAN: An excisional biopsy was taken today from the lesion on the right upper back.

Pathology: 
The first two are H&E of nodule in the fat, showing atypical cells with duct-like vacuoles. The second two are representative immunoperoxidase stains. GATA 3 is the nuclear one (dot-like pattern) and mammoglobin is the cytoplasmic staining.
These darkly beautiful photomicrographs were taken by Dr. Lynne Goldberg at the Boston University School of Medicine's Department of Dermatopathology.



Plan:  Mammography and breast ultrasound. Referral to oncologist.
Mammography shows masses in r. breast.  Ultrasound guided biopsy planned and specimen will be sent for Estrogen receptor, progesterone receptor and Her-2 (human epidermal growth factor receptor).

Note:  In this age of "Social Distancing" it is unlikely that this disgnosis would have been make expeditiously in a woman with no history of an underlying malignancy.  We will add more as her case progresses.

Your thoughts will be appreciated.

References:
1. Mammaglobin, a Valuable Diagnostic Marker for Metastatic Breast Carcinoma Zhiqiang Wang1, et. al. Int J Clin Exp Pathol (2009) 2, 384-389
Abstract:  Identification  of  metastasis  and  occult  micrometastases  of  breast  cancer  demands  sensitive  and  specific  diagnostic  markers.  In  this  study,  we  assessed  the  utility  of  a  mouse  monoclonal  antibody  to  human  mammaglobin  for  one  such  purpose.  Immunohistochemical  stains  were  performed  on  paraffin-embedded  sections  from  a  total  of  284  cases,  which  consisted  of  primary  breast  invasive  carcinomas  (41  cases)  with  matched metastases to ipsilateral axillary lymph nodes, metastatic breast carcinoma to liver (1 case) and kidney (1 case), non-breast neoplasms (161 cases), and normal human tissues (39 cases). The results showed 31 of the 41 cases of primary breast cancer with axillary lymph node metastases were positive for mammaglobin (76%). In the meantime, we documented expression of mammaglobin in occasional cases of endometrial carcinoma (17%). Our data further validated that mammaglobin is a valuable diagnostic marker for metastatic carcinoma of breast origin, although endometrial carcinoma should be considered as a major differential diagnosis. 

2. GATA3 Expression in Common Gynecologic Carcinomas: A Potential Pitfall. Tatjana Terzic  et. al.  Int J Gynecol Pathol, 38, 485-492 2019
Abstract: GATA binding protein 3 (GATA3) immunohistochemistry is primarily used as a marker of breast and urothelial differentiation, particularly in metastatic settings. In the gynecologic tract it also serves a robust marker for mesonephric and trophoblastic tumors. Full Abstract: pubmed.gov PMID: 30059453
 

Friday, January 17, 2020

Melanoma-in-Situ


This 79 yo man has a pigmented lesion that has been slowly enlarging on his right arm for around a decade.

O/E:  There is a 3 cm pigmented patch with a subtle play of color on the dorsal surface of his right arm.  The border is slightly irregular.  Dermatoscopy confirms the play of color showing variations in brown patches containing black dots admixed with reticular hypopigmented areas.





Pathology:  A 4 mm punch biopsy was taken.  This showed atypical melanocytic hyperplasia arranged in nests and single cells at and above the dermal epidermal junction and extending along the adnexae.  (Photomicrographs courtesy of Dr. Lynne Goldberg, Department of Dermatology, Boston University School of Medicine)



Diagnosis: consistent with melanoma in situ (MIS).

Questions:
1) Is it possible to suspect MIS on dermatoscopy over melanoma in this case?
2) Although excision is the preferable treatment, would Mohs, or even imiquimod be acceptable alternatives?
3) How likely is this lesion to become invasive?  It's been present now for 10 years or greater.
4) Under what circumstances would "active surveillance" be appropriate.


References:
1. M A Pizzichetta  et.al.
Dermoscopic Criteria for Melanoma in Situ Are Similar to Those for Early Invasive Melanoma. Cancer, 91 (5), 992-7 2001


2. Kevin Phan, Asad Loya. Mohs Micrographic Surgery Versus Wide Local Excision for Melanoma in Situ: Analysis of a Nationwide Database. Int. J. Dermatol 58 (6), 697-702, Jun 2019
Conclusion: Adjusted analyses demonstrated no differences in overall survival or cancer-specific survival between MIS patients treated with MMS compared with WLE.

3. Long-Term Outcomes of Melanoma In Situ Treated With Topical 5% Imiquimod Cream: A Retrospective Review
Andrew J Park et. al. Long-Term Outcomes of Melanoma In Situ Treated With Topical 5% Imiquimod Cream: A Retrospective Review. Dermatol Surg: 43 (8), 1017-1022 Aug 2017
Results: Of 12 patients with histologically confirmed MIS treated with topical 5% imiquimod cream, there were 2 recurrences (17%) during a median follow-up time of 5.5 years.
Conclusion: Although surgery is still considered the gold standard for the treatment of MIS, imiquimod may represent a potentially effective noninvasive treatment option for patient who are not surgical candidates.

4.  D Tio, et. al. Variation in the Diagnosis and Clinical Management of Lentigo Maligna Across Europe: A Survey Study Among European Association of Dermatologists and Venereologists Members. J Euro Acad Dermatol, 32 (9), 1476-1484 2018

Sunday, January 05, 2020

70 yo man with scaly plams and soles

A 70 year-old pediatric colleague from the Florida Keys sent us the following:

“I’ve been doing battle for the past few years with a rash that seemed to appear first on front of my right knee that seemed scaly, responded to clobetasol. Then, it decided to affect soles of both feet and palms of both hands,.  These were dry, thickened and split.  The fissures can be quite tender. Flares come and go over few months span.  I have noticed no pitting of my nails however I’ve either developed hypertrophic great toenails or fungus.  Topical antifungals were of no avail. The rash actually flared badly enough this last year that my great toe nails fell off. Of course they are growing back with similar thickening. I have not done KOH of any scrapings.  Topical clobetasol and moisturizing are my treatment at this time.



I am curious of your thoughts.  Please share these photos with colleagues  The were were taken after a two hour dive session.

Clinical Images:


Addendum: One of the commentators asked what medications this man is on.  The only one is tamsulosin.  Another asked about saturation diving.  No history of that.