12 yo Boy with Chest Pain and Skin Lesions

From the Department of Medicine
People's College of Medical Sciences
Bhopal,  India

Abstract: 12 year old boy with shortness of breath, intermittent chest pains and skin lesions.

History:  This 12 year-old boy was admitted to the pediatric service with a three month history of shortness of breath.  He has been having sleepless nights and we witnessed his distress in the echo room when he developed severe chest pain ( no sweating etc) and it remarkably subsided after 5 minutes of standing up after the echo examination!  He has had skin lesions since the age of four.

O/E: We saw him in the echocardiography room. On examination he had these remarkable cutaneous lesions in the elbows, legs and perianal region and over the Achilles tendons. There were reddish-yellow nodules over the extensor aspects of the knees and elbows and discrete subcutaneous nodules over the Achilles tendons.

Clinical Photos:

Lab: Serum cholesterol 641 mg%. His echo showed a global hyopkinesia with dilated left atrium and ventricles.

Diagnosis: Familial Hypercholesterolemia with Tuberous and Tendon Xanthomas.

Questions:
1. What further diagnostic studies are needed?
2. Do you think this is the homozygous variant?
3. We have yet to find a suitable explanation for his variable chest pain that aggravates only on lying down and subsides on standing. Could it be due to a myxomatous tissue near the coronary ostia?
3. What is the evidence surrounding the efficacy of drugs and even LDL apheresis for familial hypercholesterolemia?
5. What are the chances of failure to respond to therapy and what is the long term prognosis?

References:
1. Christopher Sibley and  Neil J Stone . Familial hypercholesterolemia: a challenge of diagnosis and therapy. Cleve Clin J Med. 2006 Jan;73(1):57-64
Abstract
People with familial hypercholesterolemia (FH) have dramatically high levels of low-density lipoprotein cholesterol (LDL-C), which can lead to accelerated atherosclerosis and, if untreated, early cardiovascular death. Although the heterozygous form of FH is often unrecognized, detecting it early can enable risk reduction before premature coronary heart disease occurs.  Available Free Full Text on PubMed


2. Beigel R, Beigel Y. Homozygous familial hypercholesterolemia: long term clinical course and plasma exchange therapy for two individual patients and review of the literature.  J Clin Apher. 2009;24(6):219-24
Heart Institute, Chaim Sheba Medical Center, Tel-Hashomer, Israel. beigelr@yahoo.com
Abstract
Familial hypercholesterolemia (FH) is an autosomal dominant disease. Homozygous FH (HFH) manifests with severe hypercholesterolemia since birth (cholesterol levels >5-6 the upper normal limit), which, if untreated, leads to early onset accelerated atherosclerosis and premature coronary death, usually before the 2nd or 3rd decades of life. Various invasive procedures (iliocecal bypass, porto-caval shunt, liver transplant, and gene therapy) have been introduced for lowering low density lipoprotein (LDL) aiming at reducing atherosclerosis and improving survival of HFH patients. Of all the various methods, LDL apheresis has become the most attractive. Although its impressive effect on LDL-C reduction is well established, its long-term (of more than 10 year) effect on the atherosclerotic process and specifically cardiac end-points in HFH is hardly documented. We herewith report on the longest term lipophoresis so far reported in two HFH patients, each treated with plasma-exchange and LDL-apheresis for more than 20 years. The observations provide an opportunity to focus on various aspects regarding not only the procedure itself but also its effect on various clinical endpoints. By this description together with reviewing the literature, we discuss several issues, some of them are generalized while others are individualized, dealing with the approach of long term LDL apheresis in HFH.
 

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STUMP vs. Melanoma

presented by DJ Elpern and Jag Bhawan

Abstract:  20 yo woman with two month hx of an aggressive melanocytic neoplasm.

HPI:  This otherwise healthy 20 yo college student noticed a papule on her right upper back two months before her dermatology visit.  It rubbed on her bra and that is how she found it.

O/E:  There was a 5 mm diameter brownish papule on the right upper back.  It had no play of color, no asymmetry, and the border was fairly sharp.  Dermoscopically it was not diagnositic of benign melanocytic neoplasm or melanoma.  It was definitely and "outlier" lesion and was rapidly growing.  She had an excisional biopsy the next week.

Clinical Photo:.

Pathology:  
Excisional biopsy revealed an atypical cellular lesion with a nesting pattern, especially in the upper part of the lesion ( Fig 1,2).  The deeper part showed infiltration of reticular dermis (Fig 3 ) as well as arrector pili ( Fig 4 )by islands of atypical cells. The cells were epithelioid, pleomorphic, large with atypical nuclei and several mitoses including in deep dermis ( Fig 5). Focal pigmentation was seen. There was mild epidermal hyperplasia, but no confluence or pagetoid spread of atypical melanocytes was observed. No radial growth phase was noted. These findings were interpreted as malignant melanoma with a depth of 3.5 mm.  Lack of inflammatory response, confluence and pagetoid spread raised the possibility of melanocytic tumors of uncertain malignant potential ( MEL-TUMP ).
Two of the 5 sentinel lymph nodes were positive with atypical nests of melanocytes confirmed by MART-1 within the parenchyma of the lymph nodes. 

Figures 1 - 5 in sequential order (Courtesy of Jag Bhawan)

                                                                   

                                                                         

                                                        

Surgery.  A wide-local excision and SLN biopsy was done and this showed the tumor was completely excised by the first excision and two of 5 nodes were positive.  She will have a PET scan in a few days.


Questions for Panel:
1. Is this a MELTUMP -- Melanocytic tumor of uncertain malignant potential -- also called STUMP Spitzoid tumor of uncertain malignant potential?
2. Does this impart a better prognosis than if this is a MM?  Is thickness less important for these lesions as a prognostic tool?
3. Do MELTUMPs have a different biological behaviors than MMs?
4. If PET scan is negative, would you recommend ELND?
5.  Should her care be managed at this point by an oncologist with an interest in chemotherapy.  Role for interferon?  Can this be cured by chemotherapy or is pharmacologic therapy just palliative?
6.  Many more questions.  Your thoughts are most welcome.

References:
1.  Balch CM, et al.  Multivariate Analysis of Prognostic Factors Among 2,313 Patients With Stage III Melanoma: Comparison of Nodal Micrometastases Versus Macrometastases.  J Clin Oncol. 2010 Apr 5.
Abstract  PURPOSE: To determine the survival rates and independent predictors of survival using a contemporary international cohort of patients with stage III melanoma. PATIENTS AND METHODS: Complete clinicopathologic and follow-up data were available for 2,313 patients with stage III disease in an updated and expanded American Joint Committee on Cancer (AJCC) melanoma staging database. Kaplan-Meier and Cox multivariate survival analyses were performed. RESULTS: Among all 2,313 patients with stage III disease, 81% had micrometastases, and 19% had clinically detectable macrometastases. The 5-year overall survival was 63%; it was 67% for patients with nodal micrometastases, and it was 43% for those with nodal macrometastases (P < .001). Tremendous heterogeneity in survival was observed, particularly in the microscopically detected nodal metastasis subset (from 23% to 87% for 5-year survival). Multivariate analysis demonstrated that in patients with nodal micrometastases, number of tumor-containing lymph nodes, primary tumor thickness, patient age, ulceration, and anatomic site of the primary independently predicted survival (all P < .01). When added to the model, primary tumor mitotic rate was the second-most powerful predictor of survival after the number of tumor-containing nodes. In contrast, for patients with nodal macrometastases, the number of tumor-containing nodes, primary ulceration, and patient age independently predicted survival (P < .01). CONCLUSION: In this multi-institutional analysis, we demonstrated remarkable heterogeneity of prognosis among patients with stage III melanoma, especially among those with nodal micrometastases. These results should be incorporated into the design and interpretation of future clinical trials involving patients with stage III melanoma.

2. Soonh SJ etc.  Predicting Survival Outcome of Localized Melanoma: An Electronic Prediction Tool Based on the AJCC Melanoma Database.  Ann Surg Oncol. 2010 Apr 9. [Epub ahead of print]
Abstract:
BACKGROUND: We sought to develop a reliable and reproducible statistical model to predict the survival outcome of patients with localized melanoma. METHODS: A total of 25,734 patients with localized melanoma from the 2008 American Joint Committee on Cancer (AJCC) Melanoma Database were used for the model development and validation. The predictive model was developed from the model development data set (n = 14,760) contributed by nine major institutions and study groups and was validated on an independent model validation data set (n = 10,974) consisting of patients from a separate melanoma center. Multivariate analyses based on the Cox model were performed for the model development, and the concordance correlation coefficients were calculated to assess the adequacy of the predictive model. RESULTS: Patient characteristics in both data sets were virtually identical, and tumor thickness was the single most important prognostic factor. Other key prognostic factors identified by stratified analyses included ulceration, lesion site, and patient age. Direct comparisons of the predicted 5- and 10-year survival rates calculated from the predictive model and the observed Kaplan-Meier 5- and 10-year survival rates estimated from the validation data set yielded high concordance correlation coefficients of 0.90 and 0.93, respectively. A Web-based electronic prediction tool was also developed ( http://www.melanomaprognosis.org/ ). CONCLUSIONS: This is the first predictive model for localized melanoma that was developed based on a very large data set and was successfully validated on an independent data set. The high concordance correlation coefficients demonstrated the accuracy of the predicted model. This predictive model provides a clinically useful tool for making treatment decisions, for assessing patient risk, and for planning and analyzing clinical trials.

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Nail Dystrophy in an Eight Year-Old Girl

Introduction:  In the past, we published a case of localized acrodermatitis continua.  The father of a child with this diagnosis in the U.S. came across our post on VGRD and asked our advice for his daughter.  Your opinions may help with the diagnosis and management of this child.  One can only imagine how this disorder impacts on a young child. Perhaps, one of us has had a favorable outcome with a similar patient.


History:  Please help with an opinion on our eight year-old daughter who has had an acral dermatitis for the past 5 years.   The swelling started at the cuticle and slowly moved back towards the first knuckle over the years and was associated with itching. Initially it was diagnosed as insect bites.  About a year ago her fingers became more swollen and a doctor made a clinical diagnosis of fungus (no tests were done).  She was treated first with vinegar soaks, then triamcinalone cream then Grifulvin 125mg/tsp.  None was effective and we then saw a new dermatologist who referred us to a pediatric dermatologist who she made a diagnosis: Acrodermatitis Continua of Hallopeau.  She did a fungal culture which grew out a soil contaminant that was not felt to be significant.   Our daughter is presently on clobetasol ointment.  The nail looks a bit better but not the skin.  Treatment discussions so far have included Thalidomide, Psoralen plus UVA or UVB, Acitretin, Methotrexate and others.  We know that these medications can have serious side-effects and that this disease can be resistant to treatment.  Our daughter has a lot of finger pain and can't pick up thing with her fingers.  She is only a child and we'd appreciate your thoughts.

Clinical Photos:

Questions:
1) Are there alternative diagnoses?
2) What therapies have you had success within similar cases?
3)  Any further work-up?

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Case for Diagnosis

Abstract:  11 y.o. girl with 6 month history of facial eruption
HPI:  This almost 12 yo girl has had a recurring facial eruption for ~ 6 months. In her mother's words: "At first it looked like hives. It was itchy and stung. Each day the rash changed in appearance and lasted almost 3-4 weeks. It traveled behind her ears and neck, then on to her hands and arms and finally to her chest and back. The pediatrician put her on oral steroids which did not seem to help at all.  We went to 2 dermatologists, 3 pediatricians, and an allergist/immunologist. Their opinions varied from poison ivy, to a virus, to having absolutely no idea. The only thing that seemed to work was  hydroxyzine.
The second occurrence happened in February 2010. I gave the hydroxyzine immediately and the symptoms began to disappear within 24 hours.
The next occurrence happened on March 7, 2010. She has had 3 doses of the hydroxyzine and the rash seems to be almost gone.
The patient is on no other medication and has no known allergies. We have racked our brains about everything she eats and all the products we use at home but cannot come up with any rhyme or reason.
Our pediatrician wonders if it is related to the sun......She was outside for recess yesterday and it was the first nice sunny day we have had."

Clinical Photo

Lab: Consider obtaining parvovirus B19-specific antibodies if this has not been done.  CBC was done a few months back.  This and an ANA panel will be obtained.

Questions:  What are your thoughts as to possible diagnoses?  The erythema of the cheeks suggests Erythema infectiosum, but this is almost never recurrent.

Diagnosis: This child's case was presented for ideas.  She was not seen and her parents have had problems getting an appointment with a pediatric dermatologist.  Based on the history and photograph I would consider an atypical erythema infectiosum, urticaria, a collagen vascular disease.

References: 
Musiani M, et. al. Recurrent erythema in patients with long-term parvovirus B19 infection. Clin Infect Dis. 2005 Jun 15;40(12):e117-9. Epub 2005 May 11.
Department of Clinical and Experimental Medicine, University of Bologna, Bologna, Italy. monica.musiani@unibo.it
We describe 3 patients with long-term parvovirus B19 infection (defined as detectable parvovirus B19 DNA load for >6 months after the onset of symptoms), which we monitored by serial testing for parvovirus B19 load and the presence of parvovirus B19-specific antibodies in blood. The patients showed recurrent erythema at intervals of several months.

Note:  Informed consent to present this patient's history and photograph was obtained from her parents.

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An Orphan Patient

Abstract:  44 yo man with a 10 year history of a progressive and disabling dermatitis if the feet.
HPI:  This 44 yo professional was first seen 10 years ago with a dermatitis of both feet and nails.  KOH prep from toe nails was positive for hyphae and he was treated with 3 months of Lamisil p.o.  Nails and feet improved at that time.  He was next seen in 2004 with dermatitis of both feet located on plantar areas which was predominantly hyperkeratotic with areas of excoriation.  He had developed a cellulitis of the right leg which required hospitalization.  KOH from affected aeas was negative in 2004.  Treated with betamethasone diproprionate 0.05% ointment and wet compresses and was "80%" improved in two weeks.  At that time a diagnosis of "keratoderma" and possible "dyshidrosis" was considered.  The process recurred and he asked his PCP to place him on prednisone which was done and seemed to help for a while.  From 2004 - 2010 he saw a number of other dermatologists and podiatrists both locally and at a large university center where a number of other therapies were tried, including Castelanni's paint.  None worked for very long and he was seen back at my office in March 2010.  The patient is at the end of his wits with this.  It dominates his life and is the cause of pain which interferes with his ability to stand at work.

O/E:  March 1, 2010:  Symmetrical hyperkeratosis of the plantar aspects of both feet with areas of excoriation.  Nails look normal.  Palms normal.  KOH prep from plantar dermatosis is negative for hyphae and a fungal culture was plated.

Photos March 2010:

Diagnosis:  Is this keratoderma, tylosis or an unusual contact dermatitis? Could this have begun with tinea pedis nine years ago or was than an incidental finding?

Plan:  Patch testing needs to be considered to r/o occult contact.  I doubt biopsy will help.  Will start therapy with Salex Cream (6% salycilic acid) as we await fungal culture.

Questions:  Does anyone have strong feelings about a diagnosis here?  If so, what therapy should be tried? 

Reference:
1. Shelley WB, Shelley ED.  The orphan patient. N Engl J Med. 1988 Mar 10;318(10):646. In this important letter to the NEJM, the Shelleys define the orphan as an individual “with a unique, inchoate, baffling and often disabling disease and yet clearly not discernable in the medical literature.”  While the patient described here is not strictly an "orphan patient" his 10 year unsuccessful quest for control or cure, puts him in that unfortunate category.  Your help will be appreciated.

2. Brian Maurer sent us an important review of "Shoe Dermatitis" by Robert Adams which appeared in California Medicine in 1972.  It is still valuable.

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Digital Cameras for Clinical Photography

All one needs for teledermatology is the ability to take good quality digital photos. A fine and timely review of inexpensive digital cameras appeared in the NY Times on February 4, 2010. If you are in the market for a new camera for your office, David Pogue's 2010 Review of Digital Cameras will be helpful. The Canon Power Shot, Fuji FinePix or Nikon Coolpix described in the article seem appropriate, but I'd suspect any of the cameras reviewed will serve the average physician's needs. Be sure to see the multimedia and video attachments to this article.

Henry or I will be happy to answer specific questions.

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Traction Alopecia

Abstract: 15 yo girl with one year history of alopecia
HPI: This 15 yo African-American girl has noted progressive alopecia for the past year or so. Earlier in her life her hair was in corn-rows for one to two years. She has used "relaxers" for many years but stopped ~ a year ago. Her hair was pulled back for many years. Her mother has been applying "fish oil" to the area which they think may be helping.
O/E: There is marked thinning of the hair at the temporal and occipital areas. Much less involvement on frontal and parietal areas. No inflammation, scaling or scarring is appreciated.
Photos:







Diagnosis: This is most likely " Marginal Traction Alopecia"
Questions: What would you offer this young woman as for treatment. I told her to leave her hair natural, avoid relaxers or any tension on hair.
References:
1. eMedicine.com has a good chapter on Traction Alopecia: Here is an excerpt: "Traction alopecia is a common cause of hair loss due to pulling forces exerted on the scalp hair. This excessive tension leads to breakage in the outermost hairs. This condition is seen in children and adults, but it most commonly affects African American women. The 2 types of traction alopecia are marginal and nonmarginal. Unlike trichotillomania, a psychiatric disorder of compulsive hair pulling that leads to patchy hair loss, traction alopecia is unintentionally induced by various hairstyling practices (eg, use of braids, hair rollers, weaves, twists, locks, or "cornrows"). In the initial stages, this hair loss is reversible. With prolonged traction, alopecia can be permanent. Physicians, especially dermatologists, must recognize this condition early to prevent irreversible hair loss."

2. I would recommend renting Chris Rock's documentary "Good Hair" when it is available.

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