Alkaptonuria

Alkaptonuria is an autosomal recessive disease that is a result of abnormal phenylalanine and tyrosine metabolism, characterized by excretion of large amounts of homogentisic acid (aka alkapton) in the urine, hence alkaptonuria.  The circulating HGA causes significant damage to all classes of cartilage (ergo damage to joints and heart valves), leads to kidney stones and a characteristic calcification of the annulus of the intervertebral disks which leads to a syndrome similar to bamboo spine.

It generally is either noted in infancy with discoloration of the urine, or, if undetected then, in the late thirties or early forties, when accumulation of the pigment begins to stain the sclera or, in advanced cases, the tendons.  It also can declare itself, as in this case, by chromhidrosis.  It can be excreted in the sweat glands of the face, the axillae or the areola.  

Now, to the nitty gritty.  I gave you all clues that the meds were not the problem.  I also mentioned she had a stone cold normal examination, including her axillae which were normal as pumpkin pie.  That implied her sclerae were normal.  All this means we are catching her on the front end of the clinical expression of her disease.  For two bonus points, which two countries are noted for high incidences of alkaptonuria. Finally, and most critically, I mentioned (in a separate email, which should have told you it was very, very important) she was in her late thirties.

Which question should you ask her?  Most importantly, you should ask her about dark urine, which she denies.  My next question, which was answered with a "how the hell did you know that?" look was, did she have back problems.  In fact, she had just gone to a back doc the week before and had her MRI the day before I saw her.  She was sitting rigidly straight, as if she were HLA B-27 incarnate.

Labs?  Urine HGA and a CBC, to chase down the rare bleeding diathesis.  If, for some reason, she were negative on the HGA, I would then start looking at heavy metal assays (trying to link the chromhidrosis with the tremor).  

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Delusions of Parasitosis

The Ant
by Ogden Nash

The ant has made himself illustrious
Through constant industry industrious.
So what?
Would you be calm and placid
If you were full of formic acid?

If you really want to cast a curse on someone, instead of wishing that they might live in interesting times, as the Chinese do, you may wish they would develop delusions of parasitosis.  It's a nightmare for these patients, because they so completely believe that the lint, or hair follicles they pull out, or the occasional unlucky stray ant are imbedded in their skin, and they obsess  about them,  which drives them batty. Or, to be more accurate, battier. And they can't understand why you think they're wrong.

Examination reveals linear excoriations, but no primary lesions.  Often, they go from amateur to pro and develop prurigo nodules and ulcers.  This can be the only symptom of psychiatric disease, or it can present secondarily to bipolar illness, schizophrenia, anxiety disorders, and most commonly with obsessive states such as OCD.  

It usually occurs in white middle-aged or older women, although the condition has been reported in all age groups and in men.  Morgellon Disease describes a condition characterized by the delusion of fibers being attached to the skin. Morgellon's has become a new designation for delusions of parasitosis.

Median Canaliform Dystrophy

MCD is a condition wherein the nail matrix (NOT nail bed, NOT nail plate, NOT proximal nail fold) is damaged, Often through trauma, but it can also be idiopathic or can be related to genetics.  Think of the nail as a rainbow.  It is formed as ROYGBIV and arcs across the sky, but always the orientation remains the same: ROYGBIV.  So, when you have a MCD as above, the defect is at G (in other words, pretty much in the middle of the nail matrix).  This patient also has a paronychia, but that was a red herring.  

The weird thing about these defects is that they often wax and wane, and may disappear, only to recur years later.  

Merkel Cell Carcinoma

It's kind of humbling to realize that this cancer was first described in 1972 by Toker.  The Merkel Cell is a pluripotential cell that is of neuroendocrine differentiation, and as a malignancy it tends to be rapidly growing, tends to pick elderly patients and often leads to metastasis and death.  

Nearly half the time it is on the head and neck, but can be virtually anywhere.  The prognosis is worse than that of invasive melanoma, and it has a high rate of local recurrence (one of my patients currently has that) and distant metastases occur up to 75% of the time.  

The tough thing about this clinically is that the tumors begin innocuously, and then accelerate so that by the time the patient goes from thinking it is a pimple until the time of metastasis is fairly short.  

How best to differentiate this from BCC?  If you look at the margin of this tumor, it has a "collarette" of normal skin extending onto the tumor.  BCC almost never does.  Also, it has none of the pearliness of a large nodular BCC.  Nor does it have the telangiectatic surface typical of large BCCs. 

How about SCC?  This is a much tougher call.  It certainly does not fit the keratoacanthoma picture in that there is no central crater, but a large SCC could look like this, but usually it would be more eroded, and instead of the collarette it would be more likely to be wall to wall.  This is typical of a Merkel Cell both in patient age, in location and in appearance.

Malignant melanoma Breslow's 0.6 mm, with regression 

When you look at a red octagonal street sign, you immediately know what it is and what it signifies.  The same should apply any time you see a lesion like this.  Not many things scare me.  I'm not afraid of spiders, snakes, or heights but I am afraid of anything that looks like this.  The thundercloud gray to pink look in the center of what can only be a melanoma means only one thing:  Regression.  

As you know, regression means that the lymph node has already gotten a taste of the melanoma, even though it is not very thick, and the lymph node then mounted an attack on the primary lesion.  Even in the case of a non-palpable node, it is a metastatic problem  from the moment regression is evident.  Will the metastasis kill the patient?  Maybe, maybe not, but nevertheless it is there.

All of you recognized this was a melanoma, but if you did not mention regression, you did not get full credit for this answer.  When you see a lesion like this, check their nodes and think about SLNBx and heme-onc referral.  

Probable Lid Margin Melanoma

We all see pigmented lesions on the lid margin as a matter of daily practice, and the challenge is in distinguishing between benign and malignant lesions.  This case is illustrative of the challenges which face us when we are confronted by such a lesion.

The patient presented to me yesterday and stated she had the lesion for six months or so, and that it had grown significantly over the last six months.  She had permanent eye liner put in approximately seven years ago.

Since I don't have the path yet, I will give you what I see and you can take it from there.  I see a bluish-black pigmented papule on the free margin of the lid, which looks like it extends roughly 2 mm above the surrounding skin.  It is a bit sunken in in the center, and on the conjunctival aspect of the lid, there are areas of what appears to be regression.  Extending further toward the lateral aspect of the conjunctiva, we see extension of the pigment, blue-black proximally,  jet black distally.  

When dealing with pigmented lesions of the lid, there is one rule which almost always is valid: if it extends onto the conjunctiva, it is bad.  In this case, really bad.

The only serious ddx for this (besides perhaps a cellular blue nevus) is that of a pigment granuloma, but the extension onto the conj is so unlikely in that scenario as to be eliminated as a serious consideration.

I will inform you when the dx is out, but I am at this time only giving credit for r/o melanoma.

Erythema Elevatum Diutinum

EED is a disease that looks neoplastic, but is inflammatory in nature.  Most of the primary lesions of EED are shiny, smooth papules or plaques that have the appearance of rubbed warts.  Unlike rheumatoid nodules they are mostly epidermal and dermal in appearance, as opposed to dermal and subcutaneous.  Primarily they are found over the hands and feet, knees and elbows.  

The classic histopathology of EED is a leukocytoclastic vasculitis. Attendant to the LCV is fibrosis which gives the EED papules their firm presentation.  

Associated diseases include HIV, IgA monoclonal gammopathy and other hematologic abnormalities, celiac disease, Wegener's, as well as chronic, recurrent strep infections.