Sarcoidal Granulomas

Presented by Christine Shanahan, Third Year Student
University of Virginia School of Medicine

Abstract: 36 yo male with diffuse erythematous pruritic plaques

HPI: The patient is an uninsured 36 yo male with a 6 month history of diffuse erythematous pruritic plaques on the chest, back and buttocks. The condition worsened over the past 2 months. He has no history of prior skin diseases, diabetes mellitus or other systemic conditions. He denies shortness of breath, wheezing, chest pain, eye problems, night sweats, unintentional weight loss or fatigue. He usually receives medical care in South America and frequently travels between South America and the United States.

On Examination: Diffuse erythematous pruritic plaques present on the chest, back and buttocks. No evidence of eyelid margin or oral cavity involvement.

Clinical Images:

 

Lab:

Chest radiograph showed no abnormalities.

Serum angiotensin-converting enzyme (ACE) level was found to be normal.

Recommended undergoing pulmonary function tests, ophthalmologic exam and chest CT scan.

Pathology:

Punch biopsy specimen from mid-back revealed numerous well-formed epithelioid cell granulomas in various levels of the dermis, a few patchy lymphocytic infiltrates and no necrosis or suppurative inflammation. No evidence of infectious microorganisms were found with special stains for acid-fast bacilli and fungi. Second pathologist evaluated specimen and confirmed diagnosis. Tuberculoid type of Hansen’s disease was added to histologic differential diagnosis but Fite stain showed no M. leprae.

Diagnosis: Sarcoidal granulomatous inflammation consistent with Sarcoidosis.

Plan: The patient was counseled on the importance of screening tests, including pulmonary function tests and an ophthalmologic examination, due to the insidious onset of systemic sarcoidosis and the frequency of pulmonary and ocular manifestations. The patient was reluctant to have any further workup beyond treatment of the skin condition. He was treated with 1 cc of intramuscular triamcinolone acetonide 40mg/cc (kenalog®-40) and topical steroids at follow-up visit. He was scheduled for follow-up visit in 1 month and referred for further workup of systemic disease.

Discussion:

Early diagnosis of sarcoidosis can be difficult, so cutaneous lesions can be key findings in helping to expedite this diagnosis.  Cutaneous sarcoidosis occurs in 20% to 35% of patients and can present at the early onset of disease. Also, skin involvement has been associated with more rapid progression of systemic sarcoidosis. The skin manifestations are described as specific or nonspecific lesions and are usually asymptomatic with pruritus in about 10% of patients. This patient had pruritic specific lesions with noncaseating granulomas visualized as plaques, one of the various typical morphologies. Although this patient appears to be in the early stages of the disease, the plaque presentation is typically associated with chronic forms of systemic disease. Sarcoidal lesions can mimic many other conditions including Hansen’s disease, leishmaniasis and lupus vulgaris. Specifically, tuberculoid type of Hansen’s disease is histologically similar and “the Fite method” is commonly used to distinguish the diseases. Cutaneous leishmaniasis remains endemic to many countries in South America such as Brazil, Colombia and Peru. The histopathology may be similar to sarcoidosis and some recent recommendations have been made to order PCR for Leishmania-specific DNA for any presentation of sarcoidal type granulomas in patients living in endemic areas. 

Questions:

1. Could this still be Hansen’s disease with a negative Fite stain?
2. Could this be a form of Leishmaniasis?
3. Any recommendations for further workup of sarcoidosis for a low-income, uninsured patient?  
   
   
   References:
   1) Cutaneous sarcoidosis: differential diagnosis
   Clinics in Dermatology, Volume 25, Issue 3, Pages 276-287
   Esteban Fernandez-Faith, Jonelle McDonnell
    
   
   2) Hansen's Disease: An Imitator of Cutaneous Sarcoidosis
   Katsuya Chinen, Kazuhiko Hirano, Yasunori Fujioka Pictures in Clinical Medicine. Internal Medicine Vol. 50 (2011) No. 19  P 2257-2258
   
   3) Comorbidity of Leishmania Major with cutaneous sarcoidosis 
   Moravvej H, Vesal P, Abolhasani E, Nahidi S, Mahboudi F.
   

   Indian Journal of Dermatology. 2014;59(3):316. Free PMC Article 
   
   4. The Sarcoid-Lymphoma Syndrome. (MedScape) 
   
   

Drug-Induced Lupus?

There are more things in heaven and earth then I dreamt of in our philosophy; and more things that we encounter in our offices than we can find in PubMed’s> 20,000.000 citations.

 A 35-year-old woman was started on a second course of isotretinoin for recurrent acne. Her previous treatment was two years earlier and was uneventful.  A few weeks after restarting the medication, at a dose of 0.5 mg per kilogram per day, she experienced some malaise, muscle aches, and mild joint pain. There were no new skin findings. She called me and I allowed that I had not heard of these symptoms with isotretinoin, but ordered a CBC and an ANA.

The CBC was normal, but the ANA was positive at 1:640 with a homogeneous pattern.   A PubMed search retrieved no references to drug-induced lupus and isotretinoin. However, a Google search found some anecdotal reports and a few cases of suspected DIL with isotretinoin (there were 5 alleged cases of DIL out of 27,831 self- reported isotretinoin side-effects) eHealthme.

With regards to our patient, I am going to repeat her ANA and obtain an anti-histone antibody test. If the ANA is still positive I will have her stop the isotretinoin and repeat the lab studies after 2–3 weeks. Should this likely be DIL then I think it is important that there be a report in the medical literature as undoubtedly other patients will experience this.

Dermatoscopic Pointillism

The patient is a 45 yo woman who presented with a new lesion on the right malar eminence.  It looked innocuous, perhaps, a lentigo.  The dermatoscopic image revealed a pointillist pattern.  One of our VGRD members, Dr. Phung Huynh described “pointillist nevus” some years ago.  While this is not a nevus, it shows a similar pattern.

A 3 mm punch biopsy was taken to establish what this lesion is and it is being presented for interest since I could find no reference to this phenomenon in PubMed.

For Art's Sake

Pathology: The biopsy shows a focal lichenoid lymphocytic infiltrate, scattered colloid bodies and melanophages consistent with lichen planus-like keratosis (LPLK).

 

Reference:

1. Pointillist nevi.

Huynh PM, Glusac EJ, Bolognia JL. J Am Acad Dermatol. 2001 Sep;45(3):397-400. PubMed.

2.  Dermoscopy of lichen planus-like keratosis: a model of inflammatory regression.  Bugatti L, Filosa G. J Eur Acad Dermatol Venereol. 2007 Nov;21(10):1392-7.  PubMed.

Recessive Dystrophic Epiermolysis Bullosa

We were sent the following case from Romania for suggestions.

Speranta is a 36 year-old woman from Romania who was diagnosed with Recessive Dystrophic Epidermolysis Bullosa (RDEB) at age of 6.  Initially vesicles appeared on the hands and body and then erosion and ulceration with mutilation of hands and feet. The lesions presented on the oral mucosa too. She also has difficulty with swallowing as oral feeding seems to exacerbate the lesions within the mouth. Currently the patient is cachectic. She was born in Romania and came to Germany to visit for 3 weeks. She presented in 2008 at the urgent clinic. She was referred to Freiburg University Clinic (specialized in EB) but due to the cost she was not able to stay and be treated. She does not have health insurance and she is treated only on emergency basis. For several days she has severe pain from her mutilated hands. She was treated with Flamexin powder (piroxicam) and with antiseptics. She c/o fever and chills. Over the course of the evaluation there was evidence of lesions of up to 10cm diameter, deep and greasy ulcerations, erythema and crusts on the torso, gluteal , V neck area, arms , legs and feet. There are mutilations on her feet but more severe on the hands, the fingers are unrecognizable. She has microstomia, her oral mucosa has multiple small erosions. Opening of mouth is almost impossible. Has multiple crusts over scalp.

 Bacteriology: from torso: stafilococus, multiple.  From feet and hands ulcerations: massive staf aureus.

This was a temporary inpatient visit for a patient who presented with severe pain and cachexia secondary to BE involving mucosa. She was treated with topical antiseptics and antibiotics, "antiseptic showers" and degreasing the integuments. Oral mucosa was washed with pantenol and external antiinflamtory. Due to urgent/temporary treatment and lack of insurance, genetic testing and a skin biopsy were not done. She received Clindamycin 300mg bid and due to severe pain the anesthesiologists were consulted.

Recommendations were for: a topical treatment with antibiotics: Fucidine unguent, Lomatuell, Mepithel. Oral swishes with pantenol. The pain medication to be adjusted as needed, high caloric intake d/t cachexia and control the abnormal lab values.

Social History: After she was diagnosed at age 6 Speranta was hospitalized multiple times for prolonged periods of time in hopes of finding a cure for her disease. One day when she was 16 yo she tried commit suicide by drinking a bottle of pills but her parents found her in time. Currently, she is married, bur her husband is gone most of the time from home because of his job. She is the primary care giver for her 2 little nephews (orphans from both parents) and for her sick mother and paralyzed father. What keeps her from committing suicide is that she needs to take care of her parents and these children.  Presently, she wants to be able to continue to afford her palliative medications and dressings that help her reduce the debilitating pain she has on a daily basis.  

Comment:  A few years back, we say a documentary, The Boy Whose Skin Fell Off. It was dramatic and memorable.  The woman presented here, at age 36, is lucky that she has not had invasive squamous cell carcinoma yet.  Her life must have been one long story of pain.  While we know a bit about her physical disease, we know nothing about her family or how she has managed to cope.  We suspect that her story may shed some light on her quality of life. 
 

A few of our VGRD members have a special interest in this disorder and their comments will be welcome.

Film:  Here is a link to a You-Tube of The Boy Whose Skin Fell Off. (2004, 49 minutes)

Macular and Papular Eruption in a Young Child

Two year old boy with papular eruption since birth.

HPI: The patient is a 2-3/4 year old child who presents for evaluation of lesions on the torso and face, hat have been present since birth.  Initially, the lesions were on his left TMJ area and they have generalized since then. 

The child has had many ear infections and now has tubes.  Otherwise, he has been healthy.  On direct questioning, his mother states that the lesions become red after a bath. 

O/E:  The examination shows a healthy-appearing boy. He has tan macules on the left TMJ, on the chest, the back, and a few lesions on the legs.  The lesion measure 2-4 mm in diameter.  After stroking, they appeared to urticate. 

Clinical Photos:

IMPRESSION:  This is most likely maculopapular cutaneous mastocytosis, otherwise known as urticaria pigmentosa.

Discussion:  The child is very apprehensive and the question is whether a biopsy should be done or should one observe him.  He seems healthy and at present not troubled by his lesions.  

Reference:

1. Severity of cutaneous findings predict the presence of systemic symptoms in pediatric maculopapular cutaneous mastocytosis.

Barnes M1, Van L, DeLong L, Lawley LP. Pediatr Dermatol. 2014 May-Jun;31(3):271-5.  Abstract: Although the prognosis of maculopapular cutaneous mastocytosis (MPCM), also referred to as urticaria pigmentosa, is often benign, clinicians lack evidence to reliably predict those at risk of associated systemic manifestations. We sought to elucidate clinical markers of disease severity to provide better treatment and prognostic information for individuals with MPCM. A retrospective chart review querying characteristics of children diagnosed with MPCM in the Emory Dermatology Clinic was performed. Follow-up was obtained through a clinical encounter or telephone interview. Linear regression was used to determine predictors of the number of MPCM-related systemic symptoms. Of 67 subjects, 57% were male, and the mean age of onset was 4.5 months. The maximum number of MPCM lesions was 1 to 10 in 16%, 11 to 30 in 33%, 31 to 50 in 25%, 51 to 100 in 6%, and more than 100 in 20% of subjects. For their MPCM lesions, 46% of subjects reported itching, 34% flushing, and 25% blistering. Reported systemic symptoms included diarrhea (22%), abdominal pain (15%), wheezing or dyspnea (13%), vomiting (10%), bone pain (10%), headaches (8%), cough (10%), rhinorrhea (8%), irritability (6%), and anaphylaxis (1.5%). In a multivariate linear regression analysis, the maximum number of MPCM lesions (p = 0.02) and the number of skin symptoms (p < 0.01) were statistically significant predictors of the number of systemic symptoms, controlling for age of onset, body sites involved, and sex. The correlation between cutaneous findings and symptomatology could aid clinicians in identifying individuals with MPCM who might warrant systemic evaluation and therapy.

2.  Review Article: Mast Cells, Mastocytosis, and Related Disorders

Theoharis C. Theoharides, Ph.D., M.D., Peter Valent, M.D., and Cem Akin, M.D., Ph.D.

N Engl J Med 2015; 373:163-172July 9, 2015

Dr. Theoharides reports receiving royalties from a patent (US 8,268,365 B2) related to an antiinflammatory composition for treating brain inflammation, licensed to Algonot (a portion of the proceeds is given to Tufts University under an agreement and another portion is given to to AutismFreeBrain, a nonprofit company for autism research). He also reports holding a patent (US 7,906,153 B2) related to mast cells, antiinflammatory agents, multiple sclerosis, central nervous system disorders, and a mixture of flavonoids and olive extracts, a patent (US 7,799,766 B2) related to the treatment of hormonally dependent cancers, and a patent (US 6,689,748 B1) related to a method of treating mast-cell activation–induced diseases with a proteoglycan that is licensed to Algonot. Dr. Valent reports receiving grant support from Ariad Pharmaceuticals, Celgene, Bristol-Myers Squibb, Pfizer, Novartis, and Blueprint Medicines. Dr. Akin reports receiving consulting fees from Novartis, Patara Pharma, and Blueprint Medicines and royalties from a patent (WO2003065986 A2) related to the Laboratory of Allergic Diseases 2 mast-cell line. No other potential conflict of interest relevant to this article was reported.

(I can send a pdf of this article to anyone who asks.  DJE)

3. Guidelines for the Diagnosis and Treatment of Cutaneous Mastocytosis in Children

Mariana Castells, MD,* Dean D. Metcalfe, MD,** and Luis Escribano, MD, Am J Clin Dermatol. 2011 Aug 1; 12(4): 259–270.

This excellent article is available Free Full Text online.