Wednesday, December 19, 2018

Pemphigus Vulgaris in a 43 yo Woman


The patient is a 43 yo Hispanic female. with several months of bleeding gums, sloughing tissue, and generalized oral pain.   She is otherwise healthy and takes no meds or supplements.  She has no skin or vaginal lesions.

Lab: Normal CBC and metabolic panel.

Her oral surgeon did a biopsy biopsy of normal mucosa adjacent to sloughing attached gingiva on anterior mandible and sent this for direct immunoflouresence (DIF).

Clinical Image:



Path:
H&E: Acantholysis
DIF:  Intercellular deposition of C3 and IgG.

Diagnosis: Pemphigus vulgaris

Questions:
This patient does not live close to an academic center and travel there would be difficult.
Does it make sense to initiate therapy with rituximab (if her insurance covers that) + prednisone. or should therapy be initiated with prednisone and conventional  adjunctive added later if nexessary?


References:

1. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial.
Joly P. et. al.   Lancet. 2017 May 20;389(10083):2031-2040.
This is a paper by the French study group on autoimmune bullous skin diseases.
CONCLUSIONS: 32.5% of our patients with moderate to severe pemphigus vulgaris failed prednisone and traditional CAT treatment and required rituximab therapy. Rituximab reduced the monthly prednisone intake in these patients by 73%. This suggests that a subset of patients with moderate to severe pemphigus may benefit from early institution of rituximab therapy. Rituximab significantly reduces the monthly prednisone requirement among CAT-resistant pemphigus vulgaris patients to levels on par with CAT-responsive patients.

2. Comparison of rituximab and conventional adjuvant therapy for pemphigus vulgaris: A retrospective analysis.
Agarwal A, Hall RP 3rd, Bañez LL, Cardones AR.
PLoS One. 2018 Sep 25;13(9):e0198074.  Free PMC Article
CONCLUSIONS: 32.5% of our patients with moderate to severe pemphigus vulgaris failed prednisone and traditional CAT treatment and required rituximab therapy. Rituximab reduced the monthly prednisone intake in these patients by 73%. This suggests that a subset of patients with moderate to severe pemphigus may benefit from early institution of rituximab therapy. Rituximab significantly reduces the monthly prednisone requirement among CAT-resistant pemphigus vulgaris patients to levels on par with CAT-responsive patients.

3. 
JAMA Dermatol. 2015 Aug;151(8):878-82.
Intralesional Rituximab in the Treatment of Refractory Oral Pemphigus Vulgaris.
Vinay K, Kanwar AJ, Mittal A, Dogra S, Minz RW, Hashimoto T.
JAMA Dermatol. 2015 Aug;151(8):878-82.
Abstract
IMPORTANCE:
Oral lesions of pemphigus vulgaris are usually recalcitrant and respond slowly to treatments. Corticosteroid injection is considered to be the most effective local treatment in oral pemphigus vulgaris. However, intralesional corticosteroids are not effective in all remnant lesions. In 3 such patients with pemphigus vulgaris, we evaluated the utility of 2 injections (on days 1 and 15) of intralesional rituximab, 5 mg/cm², in terms of accelerated healing, limitation of the use of systemic immunosuppressants, and reduction of their adverse effects.
OBSERVATIONS:
Three patients (1 man and 2 women) received 2 doses of intralesional rituximab in March and April 2013. All 3 patients responded to the treatment. In patients 1 and 2, the objective severity score was reduced to 0 at the final visit from a baseline score of 4 and 5, respectively (range, 0-11). The subject severity score in these patients was reduced to 1.0 and 0 from a baseline score of 22.0 and 22.5, respectively. After clinical remission was achieved, patient 3 developed a relapse of mucosal lesions. At the final visit, all of the patients were satisfied with the treatment, with a mean satisfaction score of 8 (maximum score, 10). We found a marked decline in the CD19 cell count from a pretreatment mean count of 287 cells/µL to 6 cells/µL on day 15 after a single intralesional rituximab injection. Adverse events were limited to local pain in 1 patient.
CONCLUSIONS AND RELEVANCE:
Intralesional rituximab administration lacks the adverse effects of intravenous administration. This method reduces the amount of drug administered and therefore is less expensive. Encouraging results from our study should prompt further evaluation of this novel route of rituximab administration in patients with refractory oral pemphigus vulgaris.




Monday, December 10, 2018

17 Year-old Girl with Unexplained Bruising

The patient is a 17 year-old girl whose first episode of bruising occurred after trauma sustained while playing soccer in March of 2018.  The middle child of three, she comes from a stable family.  She is an active varsity athlete.

For purposes of VGRD, the present illness consists of episodes of unexplained ecchymoses occurring every few months since March 19th, 2018.  This initial ecchymosis was tender and persisted for a month.  She has had three more episodes of bruising since then, not all related to antecedent trauma.

The patient has had poorly explained pelvic pain for two years, menometrothagia, and significant urinary retention necessitating self-catherization.  Extensive pediatric urologic evaluation at a major medical center found only a “lazy bladder.”

Other constitutional symptoms include nausea, vomiting and weight loss.  Over the past two years she has consulted multiple primary pediatricians, a pediatric endocrinologist, a neurosurgeon, a pediatric nephrologist, two pediatric urologists, a pediatric gastroenterologist, a pediatric gynecologist, a neurologist, and a pediatric hematologist. 

Thorough hematologic/coagulation workup was normal except for a minor platelet defect on electron microscopy that was felt insufficient to be causing the ecchymoses.

Two weeks ago she had another spontaneous episode of ecchymoses on her abdomen and neck, that are illustrated in photos.  Although her past ecchymoses have been tender, this most recent extensive bruise on the neck was very painful, and exquisitely tender to light touch.  Over the past two weeks these are slowly resolving.

On questioning both patient and her parents deny any adverse childhood experiences and nothing suggests a factitial etiology.

Clinical Photos:


Lab: Extensive laboratory studies have been normal.
An intradermal autoerythrocyte sensitization test has not been done yet.  Among the many studies done, an MRI showed a small pituitary microadenoma that was considered to be an incidentaloma.

Diagnosis:  The history and clinical appearance suggests Gardner Diamond Syndrome (Autoerythrocyte Sensitization Syndrome).

Questions:  GDS is a controversial diagnosis. 
1. What are your thoughts regarding this entity, especially in reference to this young woman?  She will see a pediatric rheumatologist and a pediatric  dermatologist and a pediatrician with a special interest in adolescent medicine. 
2. How can you tie together her disparate pelvic and urologic symptoms, as well as her unexplained nausea and vomiting with her bruising?

One can imagine how unsettling and scary the past two years have been for this young person and her family.  Your thoughts and suggestions will be appreciated.

Tuesday, November 27, 2018

Primary Biliary Cholangitis and Pruritus


Primary Biliary Cholangitis and Pruritis

This 57 yo woman was first seen in February 2018 for generalized pruritus.  She suffered with insomnia secondary to the symptoms. Her long-term medications include lithium, Effexor (venlafaxine) and Abilify (aripiprazole).   Because of abnormal LFTs she was referred to a gastroenterologist.  A liver biopsy “was suspicious for primary biliary cholangitis vs. primary sclerosing cholangitis.”  She was started on ursadiol 500 mg b.i.d. and cholestyramine 4 gm b.i.d. 

O/E: This woman appeared tired, depressed and older than stated age.  There were excoriated papules on her arms and legs and accessible areas of torso.

Clinical Photo:


Lab: Because of initial symptoms, CBC and Chem profile were ordered in February 2018
CBC normal
Initial Chen Profile: Alk phos 718 IU   (nl 18 – 218)
                                 SGOT 309            (nl 15 – 37)
                                 SGPT 446            (nl 15 – 56)
Repeat 10.18)          AlK Phos 319
                                SGOT  40
                                SGPT  57
                                Bilirubin has always been wnl.

Pathology: Biopsy of a papules on her right leg showed irregular epidermal hyperplasia, markedly dilated and disrupted follicles containing necrotic debris and a few PAS + spores. Gram stain negative.  DX: Perifollicular fibrosis suggestive of perforating folliculitis.

Comment:  In spite of normalization of LFTs on ursadiol and cholestyramine her pruritus did not improve.  The etiology of pruritus in PBC is unclear.  She has been started on Rifampin 150 mg b.i.d. and Narrow Band UVB.  I assume her skin lesions are secondary to PBC pruritus and excoriations. Your comments will be helpful.

Reference:
Excellent reference suggested by Dr. Richard Sontheimer:

1. A systematic approach to the management of cholestatic pruritus in primary biliary cirrhosis.  Hegade VS, wt. al.  Frontline Gastroenterol. 2016 Jul;7(3):158-166.   Free Full Text

Dr. Amanda Oakley suggested the leg lesions look like porokeratosis.  The association has been reported once in the literature.


2.Porokeratosis in primary biliary cirrhosis during plasmapheresis.  Venencie PY, Verola O, Puissant A. J Am Acad Dermatol. 1986 Oct;15(4 Pt 1):709-10.  Free Full Text.






Monday, October 01, 2018

Erosive Pustular Dermatosis of the Scalp

The patient is an 81 yo man with a long history of chronic lymphocytic leukemia.  His white counts are ~ 130,000 and platelets ~ 60,000.  He has had scores of nonmelanoma skin cancers (mostly squamous cell carcinomas) on the head and neck, torso and  all four extremities.  

He presents with yellow-brown crusts over his bald pate.  These have a mousy, earthy odor.  They were gently debrided and the subjacent areas were erosions.

Bacterial Culture:
3+ Pseudomonas
3+ Staph aureus

Clinical Images:

After initial debridement and chlorhexidine scrubs and mupirocin ointment for 33 days

Diagnosis:  Erosive Pustular Dermatosis of the Scalp

Plan: 
References:
  1. Thuraisingam T1, Mirmirani P. Erosive Pustular Dermatosis: A Manifestation of Immunosenescence A Report of 8 Cases. Skin Appendage Disord. 2018 Aug;4(3):180-186\
Abstract: Erosive pustular dermatosis (EPD) is a rare condition of the scalp and legs that is marked by crusted erosions or superficial ulcerations that may result in scarring alopecia and chronic wounds. The condition predominantly affects elderly female as compared to male patients. Its pathogenesis remains poorly understood. The majority of the cases in the literature are from the United Kingdom and continental Europe. In this series, we present 8 North American patients with EPD of the scalp, one of whom also had involvement of the legs and another with the involvement of the face. All our patients were advanced in age and had a predisposition to chronic actinic damage, which are common characteristics of EPD previously reported in the literature. We hypothesize that immunosenescence leads to an aberrant immune response to wound healing and, along with other factors such as a loss of the normal epidermal barrier, ultraviolet damage, and hormonal factors, may contribute to the development of this condition.

2 Wilk M1 et. al. Erosive pustular dermatosis of the scalp: reappraisal of an underrecognized entity. J Dtsch Dermatol Ges. 2018 Jan;16(1):15-19.
Abstract: Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory dermatosis of unknown etiology. Herein, we present a review of the disease and report our own clinical and histopathological experience in eleven patients. EPDS tends to spontaneously affect bald areas of the scalp in elderly individuals. A history of previous surgery at the same site - as observed in four of our patients - is common. Coronary artery disease, cerebrovascular insult, arterial hypertension, diabetes mellitus, and severe cases of cancer were frequent comorbidities. Most patients show an undulating clinical course despite topical anti-inflammatory treatment; in some individuals, the lesions heal with scarring. Histopathology reveals scaly crusts or erosions and granulation tissue-like changes in the dermis, evolving into a scar in more advanced stages. Apart from actinic/local damage, impaired immunity and microcirculation may be predisposing factors of the disease. Similar to pyoderma gangrenosum, EPDS must be considered in the context of nonhealing wounds in the elderly after the differential diagnoses mimicking EPDS have been ruled out. Given that previous or concomitant adjacent basal cell or squamous cell carcinoma is a common finding and that infiltrative variants extending beyond the clinically visible tumor may occur, histological mapping of the surrounding skin may be advisable in doubtful cases.

Saturday, September 22, 2018

Facial Eruption in a 2 year-old

Presented by Dr. Hamish Thain,  Dundee, Scotland
22 September, 2018

The patient is a 2 yr and 10 month old girl with a few month history of a facial eruption. It began as hive-like plaques but has evolved over the past few weeks.  Her paternal grandmother has Alpha-1 Antitrypsin disease and the child is a carrier.  No family history of collagen vascular disease.  She takes no medications save vitamins.

EXAMINATION:  The examination shows an erythematous papular and nodular eruption on both malar eminences and the left lower lid.   The remainder of the cutaneous exam is unremarkable.

Clinical Photos:
Lab:
CBC, BUN, ANA: all normal or negative.  ESR 7
Urine analysis normal

Pathology:  The slides were read by Deon Wolpowitz and the photmicrographs were taken by Erin Tabata, both of Boston University Department of Skin Pathology.
Intermittent compact hyperkeratosis with parakeratosis, intermittent basal layer vacuolization with squamatization of the basal cell layer and occasional individually necrotic keratinocytes and mild lymphocytic exocytosis, papillary dermal edema that is focally prominent in a few papillae, ectatic blood vessels, and a moderate superficial and deep perivascular and interstitial, and focally periappendageal, lymphohistiocytic infiltrate with few extravasated erythrocytes. 


Diagnosis:  Polymorphous Light variant.  This is not the common papulovesicular variant of PMLE.

Plan:  Initially, she will use broad-spectrum sun-blocks containing zinc oxide or titanium dioxide and a large floppy hat whilst outdoors.  As the season changes, and the light wanes, she should improve.  Topical corticosteroids, calcineurin inhibitors, and hydroxychloroquine will be considered if her parents want further therapy.  Phototesting at a centre is disruptive for this child, at this time.

What are your thoughts.

References
1.Alexis L. Dougherty, Cloyce L. Stetson, MD, Dr. Khachemoune. What are These Facial Plaques in a 4 year-old Child.  The Dermatologist. 8.20.2013  Link

Saturday, September 15, 2018

85 yo man with sinus tracts for diagnosis

Presented by: Dr. Neha Sagar,
Resident physician, Chhattisgarh, India

The patient, an 85 yo man with no known past medical history, presented to our OPD with large lesion with sinuses tracts on back since past 4 years. 

The lesion appeared as small sinus tracts with swelling over the right sided back.  These were pruritic in nature with  slowly & progressively increasing in size over 1 year & the lesion has not increased in size since past 3 years.   There was no history fever or cough or any other lesions noted.  He is not diabetic nor hypertensive.

No h/o specific medicinal intake or food allergy noted by the patient preceding the back lesion.

On examination:
A large lesion of approx 25 x 15 cm in size papular in nature with multiple discharging pustules noted over the same; scratch marks are present..
Swelling firm in consistency; & skin over the lesion is non-adherent to the lesion; Lesion is freely mobile over the base of scapula & muscles.

Clinical Photos:


 There are no specific systemic finding.

We approached this skin lesion as mycetoma or fungal infection; Scrofuloderma was also one of the D/D. But the skin biopsy revealed “Lobular Capillary Hemangioma.”

Path Report:
What other D/Ds can this lesion be?? 

How should we treat such lesion? How long can we treat this patient medically??
What specific counselling in terms of resolution of skin lesion should be done for the patient?
When can we consider surgical option (? wide excision); if any? What are the specific indications of the surgical removal of the lesion? 


Wednesday, July 11, 2018

Granulomatous Rosacea

A 34-year-old sociologist presented for evaluation of forehead lesions, which have been present for about 2 years.  These began about a year after her daughter's birth.  Before that, she was on oral contraceptives and was fine, but she has not been on any hormonal birth control since then.  She saw another dermatologist and was treated with topicals, a SilkPeel, Tretinoin.  She also took doxycycline for 2 – 4 weeks. Nothing helped.  She is anxious about her appearance. 

O/E:   The examination shows a pleasant, outgoing woman.  She has a somewhat pebbly appearance to the forehead with many, mostly not inflammatory discrete and confluent submillimeter papules.  There were a few erythematous papules.

Clinical Photos:


Initial Diagnosis:  I considered an acneiform eruption.  A 4 mm punch biopsy was performed.

Pathology:  Thanks to Assistant Professor Hye Jin Chung, MD from Boston University Skin Pathology for kindly providing these beautiful photomicrographs.
There is a moderate and superficial perivascular and perifollicular infiltrat.  Focal granulomas formation is noted.
                          


Presumptive Final Diagnosis: Granulomaous Rosacea
  
Discussion:  Is this really a subset of rosacea, or is it an acneiform disease sui generis? Clinically, it does not look like rosacea and it appears to be defined by dermatopathologists who only see small plugs of skin.  Similarly, perioral dermatitis is an acneiform disorder of uncertain etiology, but the diagnosis is strictly clinical.

References:
1. Lee GL, Zirwas MJ. Granulomatous Rosacea and Periorificial Dermatitis: Controversies and Review of Management and Treatment. Dermatol Clin. 2015 Jul;33(3):447-55.
Abstract: Granulomatous rosacea and periorificial dermatitis are common skin conditions affecting the face. This article examines the historical origin, causes, clinical presentation, and management strategies for these entities.  Link to Full Text.

2.
Omar Khokhar and Amor Khachemoune. A Case of granulomatous rosacea: Sorting granulomatous rosacea from other granulomatous diseases that affects the face. Dermatology Online Journal 2004 10 (1): 6  Free Full Text.
Abstract: Granulomatous rosacea is a variant of rosacea that may present similar to other granulomatous diseases. We present the case of a 45-year-old woman with a 2-year history of facial erythema with multiple papules and pustules on the cheeks, chin, and glabella. The patient responded to minocycline, resulting in healing 6 months without residual scarring. This patient's clinical and histological presentation and treatment outcome are to our assessment consistent with granulomatous rosacea. However, other clinically and histologically related entities will be discussed. These entities include, but are not limited to, perioral dermatitis, granulomatous periorificial dermatitis, lupus miliaris disseminatus faciei, facial afro-caribbean eruption syndrome, and sarcoidosis.


Sunday, July 08, 2018

Solitary Tricholemmoma

The patient is a 39-year-old home visitor who presents for evaluation of a lesion on the bulb of
the nose that has been present for about six months.

O/E: The examination shows a healthy, outgoing woman with type I skin. There is a solitary 3 mm in diameter dome-shaped papule with a central keratin on the bulb of the nose. The remainder of the cutaneous examination is unremarkable.
Clinical and Dermatoscopic Images: 

Preoperative diagnosis: This has the appearance of keratoacanthoma, squamous cell carcinoma, or hypertrophic actinic keratosis.

PLAN: The lesion was shave excised. The base was lightly electrodesiccated and curetted and a
specimen was submitted for pathology.

Pathology: Assistant Professor Hye Jin Chung, MD from Boston University Skin Pathology kindly provided the photomicrographs.

At x4:  parakeratosis, papillomatosis and a lobular proliferation of pale cells
At x10: peripheral palisading with focal eosinophilic hyaline basement membrane
Diagnosis:  Solitary Tricholemmoma

Daignosis:  Solitary tricholemmoma.  Tricholemmomas can be a marker for Cowden's disease.  However, I don't feel that a solitary tricholemmoma is a red flag in a 39 yo woman.  I asked the patient about a personal or family history of cancer and there was no history of thyroid, lung or colon.

This case is presented because there are few to no accessible cases of solitary tricholemmoma online and no dermatoscopic images that I could fine..

Reference:

Spiegel JH, Khodai N. Tricholemmoma of the nose. Am J Otolaryngol. 2006 Nov-Dec;27(6):430-2.

Abstract

OBJECTIVES: The objectives of this case report are to (1) identify clinical presentations of tricholemmoma, (2) discuss the characteristics of Cowden syndrome and the relationship between this syndrome and tricholemmoma, and (3) differentiate tricholemmoma from other superficial cutaneous tumors such as basal cell carcinoma and granulomas.

RESULTS:

Tricholemmoma was first described as a cutaneous neoplasm in 1962. It is associated with the Cowden syndrome and can be misdiagnosed as a more aggressive cutaneous malignancy. We report an unusual case of tricholemmoma presenting as a nasal mass.

CONCLUSIONS: Tricholemmoma is described as having a predilection for the head and neck, yet little information has been published about this disorder within the Otolaryngology literature. Otolaryngologist-head and neck surgeons must be familiar with this neoplasm because it can be frequently misdiagnosed as an aggressive cutaneous malignancy and hence can be incorrectly treated. We describe the presentation and diagnosis of tricholemmoma, describe the frequent association of this neoplasm with Cowden syndrome, and report an unusual presentation of tricholemmoma as an intranasal mass.

Tuesday, July 03, 2018

Renal Transplant Patient with a Black Toe

The patient is a 70 yo man who had a renal transplant around 10 years ago.  His immunosuppression consists of oral tacrolimus and prednisone, and he is seen annually by a dermatologist.  He had a 3 cm superficial squamous cell carcinoma ofhis scalp 5 years ago that was treated successfully with topical 5FU.

O/E: The current exam revealed a black area under the nail of the second toe on the left foot.  He said it's been like his for around a year and has not changed much.

Clinical and Dermatoscopic Images:
Diagnosis and Discussion:
While I am pretty certain that this is a subungual hematoma; if his history is accurate that may be worrisome.  There is little downside to removing the nail and biopsying the nail base if it is pigmented and this was scheduled in a week's time.  The fact that this is Morton's toe also favors subungual hematoma.

Thursday, June 21, 2018

44 yo woman with facial erythema


HPI: The patient is a 44 yo health care professional with an 18 month history of erythema of the chin and perioral area.  She has been seen by four dermatologists who have treated her for rosacea and perioral dermatitis with doxycycline and various topicals.  Nothing has helped.  The process began after her  mother died.  She lives at home with her boyfriend of 16 years and their two preteen children.  
She admits to being anxious and depressed as there are significant social problems at home.
She used a topical steroid for a few days when her lips were prurituc, not for weeks to months.
She takes no medications p.o. other than Xanax 0.25 mg h.s. There is no history of using a mask or any local contactant to this area that might explain this pattern.

O/E:  Shows a light-complected Caucasian with sharply demarcated erythema and mild scaling of the chin, and submental region.

Clinical Images:

 Patch Testing: True Test negative at 96 hours

 Discussion:  This is a perioral rash that does not look like perioral dermatitis.  The pattern suggests a contact dermatitis, but the history and patch testing do not corroborate that.  Perhaps, one of our readers will have had a similar patient.  At present, this is medically unexplained, but I suspect that I am missing something.

Addendum:  See comments of Dr. Howard Maibach.

Wednesday, June 06, 2018

DPP4-Inhibitor Drug-Induced Bullous Pemphigoid

The patient is a 68 yo woman with Type II diabetes and Stage IV renal failure who presented with a four month history of intense generalized pruritus.  Her PCP had treated her for scabies without effect.  Her medications  include Lantus, lisinopril, atorvastin risperadone  and Januvia (sitaglipin).  The Januvia was the  most recent new medication and it was started a month or two before she started to itch.

O/E:  there was a wide-spread dermatitis on torso and extremities.  No frank bullae but there was a suggestion of vesicles.  No burrows were seen.  Vesicles were noted on the palms and soles.

An eliptical biopsy was done as well as a 3 mm punch biopsy from perilesional skin for DIF.

Histopath showed: Eosinophilic spongiosis and spongiotic vesiculation.
DIF was positive for IgG in a linear pattern at the DEJ
Histological Photographs courtesy of Dr. Jag Bhawan, Boston University SkinPath Laboratory



Diagnosis:  Bullous Pemphigoid secondary to DPP-4 inhibitor.  

Discussion: DPP-4 inhibitors  are a class of drugs that are used for Type 2 diabetes.  There have been eight references to BP as a cutaneous drug effect DPP-4 inhibitors in PubMed (the first was in 2016).  It is clear that we will be seeing more of these patients what with the wide-spread usage of DPP-4 inhibitors.

Acknowledgement:  Special thanks to Rick Sontheimer, M.D. who alerted me to this phenomenon and Dr. Jag Bhawan for the pathology interpretation and the beautiful photomicrographs.


References:
 1. Bullous Pemphigoid Associated with the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin in a Patient with Liver Cirrhosis Complicated with Rapidly Progressive Hepatocellular Carcinoma. Harada M et. al.  Intern Med. 2017 Sep 15;56(18):2471-2474  Free Ful Text

2. Dipeptidyl peptidase IV inhibitors, a risk factor for bullous pemphigoid: Retrospective multicenter case-control study from France and Switzerland.  Benzaquen M, det. Al.. J Am Acad Dermatol. 2018 Jun;78(6):1090-1096
CONCLUSIONS: DPP4is, especially vildagliptin, are associated with an increased risk for development of BP. Their use needs to be carefully evaluated, particularly in high-risk patients, such as males and those age 80 years or older.  Full Abstract.

3. Vildagliptin significantly increases the risk of bullous pemphigoid: A Finnish nationwide registry study. O. Varpuluoma et. al. J. Invest Dermatol:
Volume 138, Issue 5, Supplement, Page S46, 2018.  Full Abstract (Supplied by Rick Sontheimer)