Erythema Migrans: Classic Lyme

Presented by Yoon Cohen, D.O. and David Elpern, M.D.

Abstract:  38-year-old man with history of tick bite and expanding annular lesion

HPI: The patient is a 38-year-old man with a 4-day history of and expanding red annular patch on the right inner thigh. He had a tick bite in this area ~ 10 days prior. He has not been treated with any antibiotics at this time and has had denied no flu-like or other associated constitutional symptoms.  He lives in an endemic area and has had many tick bites in the past.

O/E: The skin examination showed a healthy and pleasant man with a well-defined 15 cm pink to red annular patch with a central pink oval shaped patch on his right thigh.  It has a "bull's eye" appearance.  There are no other cutaneous findings.

Clinical Photo:

Diagnosis: Erythema Migrans (Early Lyme Disease)

Discussion: 
Lyme disease is caused by the spirochete Borrelia burgdorferi. Erythema migrans is the most common clinical manifestation of Lyme disease. It typically develops 7-14 days after tick detachment and is characterized by a rapidly expanding, erythematous annular patch or plaque. 

The diagnosis of erythema migrans is based on the clinical presentation and history of recent exposure in the endemic regions. Although the skin lesion cannot be considered pathognomonic of Lyme disease, erythema migrans is so distinctive that serologic testing for antibodies against B.burgdorferi is generally unnecessary. These serologic tests have high false negative results in as many as 60% of cases.

Treatment for Lyme disease depends on the stage. If there is only a tick bite, single dosage of doxycycline 200 mg is considered adequate if administered within 2 - 3 days.  However, if a patient presents with erythema migrans, doxycycline 100 mg twice daily for 14 days (range, 10 to 21 days) is currently advised.  (Amoxicillin is an alternate treatment).  For secondary and tertiary Lyme disease the treatment can be more complex.

The references below give much more detailed information.  Post-Lyme Disease syndrome is controversial and has generated a lot of ink.  See Michael Spector's fine New Yorker piece referenced below.
 

Reference:
1. Early Lyme Disease
Gary P. Wormser, M.D.
N Engl J Med 2006; 354:2794-2801
(This is an extremely helpful article.  Although it is seven years old, little has changed re garding hte literature on chronic Lyme disease.  If you can't get access to the full text of this article, we will send you a pdf.)

2.  Annals of Medicine

The Lyme Wars

The Lyme-disease infection rate is growing. So is the battle over how to treat it.

by Michael Specter The New Yorker July 1, 2013
This is in the current New Yorker as we prepare this post.  It is a level-headed review of Lyme disease from a top science writer.  This article will help the public as well as physicians. 

3.  Patient Friendly Material. 

Vesiculobullous eruption in a three year-old

Presented by Dr. Yogesh Jain

History: A 3 year old girl presented with vesiculobullous lesions mainly over neck, upper back, right iliac region, scalp & few over abdomen & lower leg for the past week.
There was a history of fever 7 days ago that lasted for 5 days, high grade, more at night.  No loss of appetite, normal sleep, bowel & bladder habits.
Her elder brother had similar lesions over the scalp 3 weeks back, for which, he has received treatment & was cured.

O/E: She was afebrile with normal general & systemic exam. The vesicles were tense, & on rupture, producing a yellowish watery discharge, somewhat itchy, forming a scaby base with circumscribed borders.

Clinical Photos:

Diagnosis:  We are asking your help for this.

Melanoma Does Not Read Textbooks I

Presented by Yoon Cohen, D.O. and David Elpern, M.D.

Abstract:  67-year-old man with a 3-month history of pigmented papules on the face and torso.

HPI: The patient is a 67-year-old man with a 3-month history of pigmented papules on the face and torso. He has past medical history of enucleation over 19 years ago for ocular melanoma. Since enucleation, he has been fairly healthy and staying active with his life. He has not noticed any recent weight loss, fatigue, and other associated constitutional symptoms.

O/E: The skin examination showed a pleasant and outgoing man with ~ 50 well defined 2-4 mm multiple scattered purple to blue-black firm papules on the face and torso. No lymphadenopathy noted. 

Clinical Pictures: 

Purple to blue-black firm papules on the cheek

Several scattered pigmented papules on the upper back

Dermoscopic View

Pathology: A dermal nodule of atypical, focally pigmented epithelioid cells exhibiting large nucleoli and focal tumor necrosis infiltrating the dermis and skeletal muscle consistent with metastatic malignant melanoma. No junctional component is present. Immunoperoxidase staining reveals the tumor cells to be positive for Mart-1/Melan-A, S100 and HMB45, confirming the histologic diagnosis.

Lab: CBC abd chemistries are normal. LDH is borderline high but not above normal range.

Imaging Studies: 

1. Abdominal Ultrasound: There are numerous heterogeneously hyperechoic masses within the liver, most compatible with metastatic disease. The largest of these is within the right hepatic lobe and measures up to 6.6 cm in greatest diameter. 

2. Chest PA/Lateral Xrays: No pulmonary nodules or pleural effusions are evident.

Diagnosis: Metastatic melanoma. Most likely ocular melanoma metastasis to the liver.

Discussion: 

This patient poses some therapeutic question.  His melanomas do not bother him at this point and he keeps saying that he feels fine.  He's an avid golfer.  If he gets plugged into the system and loses this season; can we promise him another season in 2014?  He is a simple man; retired, no outside source of income. His melanoma, dormant for 19 years is suddenly active again. Why?

Question:

Knowing chemotherapy may significantly affect his energy level and he may experience other significant side effects, we are not sure what would be the best option for this patient at this point. We'd appreciate you sharing your similar experiences with your patients.

Follow-up: Many attempts were made to contact the patient and get him back for a follow-up discussion; but he never answered his phone or returned letters.  He died ~ 5 months later.  We hope he payed a few rounds of golf over the summer and suspect that his life was easier without futile attempts at palliation.

References:
1. Progression of ocular melanoma metastasis to the liver: the 2012 Zimmerman lecture.
JAMA Ophthalmol. 2013 Apr;131(4):462-9. 

Grossniklaus HE.

Source

L. F. Montgomery Laboratory, Emory Eye Center, Atlanta, GA 30322, USA. ophtheg@emory.edu

Abstract

IMPORTANCE:

To the best of my knowledge, this study demonstrates for the first time small, apparently dormant micrometastasis in the liver of patients with uveal melanoma.

OBJECTIVE:

To evaluate the histological and immunohistochemical findings in metastatic uveal melanoma to the liver.

DESIGN:

Samples of liver were obtained at autopsy from patients who died of metastatic uveal melanoma to the liver.

SETTING:

L. F. Montgomery Laboratory, Emory Eye Center, Atlanta, Georgia.

PARTICIPANTS:

A total of 10 patients who died of metastatic uveal melanoma to the liver.

INTERVENTION:

Sections of the liver were examined with hematoxylin-eosin, periodic acid-Schiff, Masson trichrome, or reticulin stains.

MAIN OUTCOME MEASURES:

The tumors' morphology, growth pattern, mean vascular density, and mitotic index were determined with the aid of immunohistochemical stains for S100, HMB45, CD31, and Ki67.

RESULTS:

Stage 1 metastases (defined as tumor clusters ≤50 μm in diameter) were identified in the sinusoidal spaces of 9 of 10 patients (90%). Stage 1 metastases were avascular and lacked mitotic activity. Stage 2 metastases (defined as tumors measuring 51-500 μm in diameter) and stage 3 metastases (defined as tumors measuring >500 μm in diameter) were found in all patients. Immunohistochemical stains were positive for S100 or HMB45 in all tumors. Overall, stage 1 metastases outnumbered stage 2 metastases (which outnumbered stage 3 metastases). The mean vascular density and mitotic index increased from stage 2 to stage 3 metastases (P < .05). The architecture of stage 2 metastases mimicked the surrounding hepatic parenchyma, whereas stage 3 metastases exhibited either lobular or portal growth patterns.

CONCLUSIONS:

Uveal melanoma that spreads to the liver can be categorized as stage 1 (≤50 μm in diameter), stage 2 (51-500 μm in diameter), or stage 3 (>500 μm in diameter) metastases. The later stage exhibits a lobular or portal pattern of growth. During this progression, tumors become vascularized and mitotically active.

2. Domancy of Metastatic Melanoma

Pigment Cell Melanoma Res. 2010 Feb;23(1):41-56. 

Ossowski L, Aguirre-Ghiso JA.

Source

Division of Hematology and Oncology, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA. liliana.ossowski@mssm.edu

Abstract

Metastatic dormancy of melanoma has not received sufficient attention, most likely because once detectable, metastasis is almost invariably fatal and, understandably, the focus has been on finding ways to prolong life of patients with overt recurrences. Nevertheless, analysis of the published clinical and experimental data on melanoma indicates that some aspect of melanoma biology imitate traits recently associated with dormancy in other solid cancers. Among them the ability of some melanomas to disseminate early during primary tumor progression and once disseminated, to remain undetected (dormant) for years. Comparison of cutaneous and uveal melanoma indicates that, in spite of being of the same origin, they differ profoundly in their clinical progression. Importantly for this discussion, between 40 and 50% of uveal melanoma remain undetected for longer than a decade, while less than 5% of cutaneous melanoma show this behavior. Both types of melanoma have activating oncogene mutations that provide autonomous pro-proliferative signals, yet the consensus is that those are not sufficient for tumor progression. If that is the case, it is possible to envision that signals from outside the tumor cell, (microenvironment) shape the fate of an individual disseminated cell, regardless of an oncogene mutation, to progress or to pause in a state of dormancy. To stimulate further debate and inquiry we describe here a few examples of potential signals that might modify the fate of disseminated cell and provide brief description of the current knowledge on dormancy in other cancers. Our hope is to convince the reader that disseminated melanoma cells do enter periods of prolonged dormancy and that finding ways to induce it, or to prolong it, might mean an extension of symptoms-free life for melanoma patients. Ultimately, understanding the biology of dormancy and the mechanisms of dormant cell survival, might allow for their specific targeting and elimination.

Abstract:  53 yo carpenter with generalized dermatitis

HPI:  The patient has has a five week history of a dermatitis on the face, torso and lower legs.  He is in good general health and on no new medications.  Only oral med is lisinopril.  For the past two months he has been working indoors mainly with Western Knotty Cedar and has been exposed to dust from that.  He wondered if this could be a cause.  He's had cbc, chem profile done by his nurse practitioner and all was normal.

O/E:  Fiery erythema of face (sparing lower lids), chest, back (sparing axillary vaults) and less advanced dermatitis of legs.  Doubly covered areas appear spared.  Generalized scaling on the scalp.

Clinical Photos (shown with patient's permission):

Diagnosis:  The patient's suspicion may be right.  This could fit with airborn allergic contact dermatitis from cedar.

Reference:1. Allergic contact dermatitis from cedar wood (Thuja plicata) Bleumink E, Mitchell JC, Nater JP. Br J Dermatol. 1973 May;88(5):499-504.

SUMMARY:  A case of allergic contact dermatitis caused by the heart-wood of western red cedar (Thuja plicata) is reported. The workman, after exposure to woods for 2 years in a mill, developed an acute dermatitis of his face, hands and arms. Avoidance of contact with wood cleared the symptoms. Patch tests with extracts of nineteen different wood species revealed a strong reaction to western red cedar. Patch tests with the various components present in the wood showed positive reactions to gamma-thujaplicin, y-hydroxy-isopropyltropolone and also to thymoquinone. Although thymoquinone was found to be a strong skin irritant, tests performed in two other patients with eczema indicated thymoquinone to be a potent allergcnic component as well.

2.  Airborne contact dermatitis - current perspectives in etiopathogenesis and management.  Handa S, De D, Mahajan R.  Indian J Dermatol. 2011 Nov;56(6):700-6. Full Free Online

Source: Departments of Dermatology, Venereology, and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India .

Abstract: The increasing recognition of occupational origin of airborne contact dermatitis has brought the focus on the variety of irritants, which can present with this typical morphological picture. At the same time, airborne allergic contact dermatitis secondary to plant antigens, especially to Compositae family, continues to be rampant in many parts of the world, especially in the Indian subcontinent. The recognition of the contactant may be difficult to ascertain and the treatment may be even more difficult. The present review focuses on the epidemiological, clinical and therapeutic issues in airborne contact dermatitis.