fferential diagnosis

8/6/2019 Fferential Diagnosis

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fferential Diagnosis

1. Persistent ecchymosis

2. Postinflammatory hyperpigmentation

3. Cutaneous malignant melanoma metastasis

4. Pigmentary changes due to endocrine and metabolic disease

5. Drug-induced pigmentation

1. Persistent ecchymosis can occur when there is prolonged or repeated trauma to soft tissue.

Ecchymosis, or generalized bruising, occurs with diffuse extravasation of blood from a ruptured

vessel into subcutaneous tissue. Subsequent discoloration of skin occurs, with changes from

deep purple to a lighter violaceous color and eventual yellow pigment over a period of days to

even weeks, depending on the severity of trauma. Location and distribution of the discoloration is

also affected by gravity. In this case, even though most of the pigment changes occurred in the

lower extremities, there was no migration of pigment or color change.

2. Postinflammatory hyperpigmentation(PIH) is an acquired excess of pigment that occurs due to a

multitude of disease processes or therapeutic interventions. These include allergic reactions,infections, phototoxic eruptions, trauma, and inflammatory conditions. PIH occurs via either

dermal or epidermal melanosis (Schwartz & Kihiczak, 2009). PIH is seen more commonly in

darker-pigmented individuals and distribution occurs at the site of original inflammation. Lighter

pigmentation generally corresponds to epidermal melanosis, while deeper, darker pigment

indicates dermal melanosis.

3. Cutaneous malignant melanoma metastasisrepresents the progression of malignant melanoma

from an in situ lesion through its radial and vertical growth phases. It is during the vertical growth

phase when the process of metastasis generally occurs in a predicted fashion, beginning with the

primary site progressing to regional sentinel lymph nodes to systemic involvement (Leong, 2006).

Pigment changes in the skin of various colors (blue, brown, black, red) occur as tumor cells

migrate through the epidermis and dermis at various speeds and directions.

4. Pigmentary changes due to endocrine and metabolic diseasewill require evaluation through

history and physical examination along with laboratory work-up. In many cases, these pigmentary

changes are similar or even identical to those related to drugs. Blue-grey or grey pigmentation

can be seen in Addison disease, hemachromatosis, and Wilson disease. Addison disease, a

disease of adrenocortical insufficiency, occurs from the destruction or dysfunction of the adrenal

cortex. Hyperpigmentation, often described as "muddy," can occur in skin, scar tissue, and

mucous membranes and may be the only presenting sign of this disease for months or even

years. The pigmentation may be generalized although there is a predilection for sun-exposed

areas, elbows, knees, axilla, areola, palms, soles, extensor surfaces, oral, vaginal, and perianal

mucosa. Laboratory work-up may include the following: ACTH stimulation test, rapid

adrenocorticotrophic hormone test, electrolytes (to ascertain hyponatremia or hyperkalemia),

BUN, creatinine, calcium, blood sugar, liver function tests, complete blood count, and thyroid

stimulating hormone (Griffing & Odeke, 2008). The blue-grey metallic or "slate-grey" skin

pigmentation seen with Wilson's disease and hemochromatosis is also generalized, but generally

is a late finding. It may also be bronze in color. This pigment occurs as a result of both iron

deposition and melanin. Confirmation of diagnosis with laboratory testing includes ferritin and

trans-ferritin saturation levels, copper, or ceruloplasmin levels.

5. Drug-induced pigmentation is the correct answer. There are many drugs which, when directly

deposited in the skin, can cause pigmentary changes. Hydroxychoroquine, chloroquine,


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quinidine, and quinacrine can cause a blue-black pigmentation of the extremities, face, oral

mucosa, nails, and ear cartilage. The most common area affected is the pretibial surfaces.

Amiodarone, a photosensitizer, can dyspigment the skin in sun-exposed areas after months of

use. Zidovudine tends to cause a brown or blue pigmentation most often seen in the nails but

may also be seen less commonly in a diffuse pattern on the skin and tongue. Chlorpromazine,

imipramine, clomipramine, and thioridazine may also show slate-gray pigmentary changes with

prolonged use. Heavy metals, such as silver, gold, and bismuth can also cause irreversible slate-

grey pigment with very prolonged exposure. However, the most common offender, as seen with

this patient, is minocycline.

Minocycline, a member of the tetracycline family, is a broad-spectrum antibiotic first introduced in 1967.

Although adverse effects, such as abnormal pigmentation are uncommon, it is a well-recognized potential

side effect of this f requently used acne medication. The onset of minocycline-induced pigmentation may

occur after only small doses, but typically is delayed until a dose of > 50 g is reached. A stippled, blue-

grey, blue-black, or slate/grey macular pigmentation is most commonly seen. There are three types of

pigmentation; Type I is the most common. This blue-black pigmentation appears as areas of prior

inflammation such as acne, surgical scars, or prior areas of trauma. Type II shows dyspigmentation on

normal skin, usually the pre-tibial surfaces. Often mistaken for bruises, the pigment does not fade as

expected. This type seems to be dose related and generally occurs after months or years of treatment

with minocycline. Type III, the rarest type, is also generalized but seen in greater abundance in sun-

exposed areas and is usually symmetric. This pigment tends to be more "muddy brown" in color. Types I

and II may also be found in ear cartilage, nailbeds, oral mucosa, nails, sclera, thyroid, teeth, and bone.

Drugs for oral lichen planus

Many systemic and local drugs have been described for treatment of OLP.

Corticosteroids

Topical. Topical corticoids are the drugs of first choice for localized and symptomatic lesions.[6] Fluorine

steroids, especially fluocinolone acetonide, seem [1]to be better absorbed in the oral epithelium. They

should be used in ointment or gel because they are hydrophilic and are better absorbed by the oral

mucosa, although the gel can be irritating.[7] Occlusive corticoids, like those with Orobase (Colgate-

Palmolive, New York, NY) as the vehicle, mitigate the discomfort. Sometimes they must be used with

other corticoids to increase their potency. Steroid in spray form was preferred in a study comparing

fluticasone propionate spray and betamethasone sodium phosphate mouthrinse.[8]

Elixir. The most widely used medication is dexamethasone elixir at 0.1 mg/mL, swirling approximately 5

mL for 3 minutes four times a day and then spitting out.[9]

Inhalants. Inhalants are not used much for oral lesions because they are more appropriate for lesions inthe esophagus.[10]

Oral. This form is indicated for erosive OLP and other disseminated forms. The initial dose should not be

less than 20 mg prednisone or equivalent. The recommended dosage is 30-40 mg/d for 4-6 weeks or until

improvement of the symptoms, reducing slowly to 20 mg, which should be maintained until complete

remission.[11] With this scheme, recurrence is less frequent.[2] The oral prescription is usually associated

with topical treatment.


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Intralesional Injections. Injections are seldom used because of the associated pain. The recommended

dose is 10 mg/mL triamcinolone acetonide for cases of erosive and located OLP. [4] Atrophy and

pigmentation may occur, and in those cases treatment should be discontinued.[12]

Retinoids

Topical. Results with isotretinoin 0.1% gel were considered good,[13] although there was local irritationthat was easily controlled by decreasing the frequency of applications. Other authors14 noted that despite

the efficacy of this drug, recurrence was frequent after the interruption and the response was slow in

cases of erosive LP. Due to its regulatory action on growth and differentiation of keratinocytes and on

inflammation, topical tazarotene has been used with good results in hyperkeratotic OLP.[15]

Oral. Acitretin in doses used for psoriasis has been used at levels of 10-30 mg/d with reports of cure in

90% of patients in up to 19 months. Some report good results with 0.25 mg/kg/d in only 2 months of

treatment.[16]Etretinate (not available in Brazil anymore) in a dosage of 10-20 mg also had a good

response, although some recommend higher dosages, up to 75 mg/d, for better results.[17]

Griseofulvin

Griseofulvin has been used empirically but with good results. Its action seems to be related with the

nucleic acid metabolism, which is important for the normal keratinocytes. The dosage used ranges from

250-500 mg/d for 8-10 weeks.[18] More studies are needed to further evaluate its efficacy.[19]

PUVA Therapy

This was used by some authors with favorable results[20,21](mainly in cases of OLP with extensive

cutaneous lesions). The risk-bene-fit balance should be considered due to the drug's side effects[22] and

because OLP is a benign lesion and the risk of carcinogenesis exists.[23]

Cyclosporine

Its effect in LP is explained by the action in the T lymphocytes. Despite the good results described by

some authors, it should be considered as a last resort due to its side effects and the need of high

dosages (3-5 mg/kg/d) for control of the disease. Some report the use of cyclosporine 500 mg in the form

of a daily mouth swirl with good results and without side effects.[24,25] Other studies do not show

advantages of topic cyclosporine when compared with topic corticoids.[26]

Azathioprine

Azathioprine may be used in association with steroids in cases of bullous LP and in severe forms of the

disease as a cor-ticoid-sparing drug.[27]

Antibiotics

Many antibiotics have been used without good response. Tetracycline associated to nicotinamide is

described as efficient in cases of bullous LP.[28] It may be used topically in the form of mouth swirls using

250 mg in 100 mL water 2-3 times a day for erosive LP.[29]

Dapsone

Doses of 100-150 mg/d dapsone are indicated for bullous LP, but up to 200 mg may be administered.[30]


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Surgery and Laser

These are options in symptomatic and hypertrophic cases that are unresponsive to other treatments.

Excision with closing, electrosurgery, or cryosurgery may be used. Carbon dioxide laser has been used in

cases of OLP in plaque, but recurrence was high.[31]

Extra-Body Phototherapy

This therapeutic modality has been used more recently, twice a week during 3 weeks, especially for

erosive LP.[32]

Immunomodulation Treatment

The use of immunomodulators, like levamisole, is indicated by some authors as an adjuvant therapy to

prednisone in patients with symptomatic and difficult-to-treat LP. Levamisole seems to have

immunomodulating properties, which would justify its results in LP. [33] One researcher[34] suggests

administration of immunomodulators, such as levamisole and interferon-, in patients with idiopathic LP

without symptoms of systemic diseases. Tacrolimus is a drug with powerful immunosuppressing effects

used initially for patients receiving organ transplants. It has been used in cases of symptomatic LP,especially for the erosive form, with good results[35] in symptom relief, despite frequent recurrences.[36,37]

Metronidazole

A recent report[38] described the use of 500 mg metronidazole twice a day for 20-60 days in patients with

generalized idiopathic LP with satisfactory results in 78.9% of cases. Its action may be explained by its

immunomodulator and antimicrobial effect. Other therapies have been used without any scientific

confirmation.

Antiarrhythmic Actions ofAmiodarone: A Profile of aParadoxical AgentBramah N. Singh*

Division of Cardiology and the Department of Medicine, Veterans Affairs Medical Center and the Department of

Medicine, University of California, Los Angeles, School of Medicine, Los Angeles, California, USA

Available online 12 October 1998.

Abstract

Amiodarone, a complex compound with variegated electropharmacologic and pharmacokinetic properties and an

equally complex side-effect profile, continues to have a critical role in the control of ventricular and

supraventricular tachyarrhythmias as the use of class I agents has declined. Such is also the case with sotalol.

Unlike other so-called class III agents,amiodarone non-competitively blocks sympathetic stimulation, and its effects

on repolarization are not associated with reverse use dependency. Rarely does it produce torsades de

pointes despite its propensity to induce significant bradycardia and marked prolongation of the QT interval. During

long-term therapy with the drug, there is no impairment of ventricular function; in fact, there are significant increases

in the left ventricular ejection fraction during protracted amiodarone therapy in patients with heart failure. Long-

termamiodarone administration consistently demonstrates marked efficacy in a wide spectrum of arrhythmias. The

major limitation of amiodarone during long-term therapy is its unusual side-effect profile, although the increasing

trend for low-dose drug therapy has demonstrated a major decline in the overall incidence of serious adverse

reactions. Amiodarone is effective in controlling symptomatic ventricular tachycardia and fibrillation (VT/VF) in >60


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70% of patients when conventional agents (especially class I) are ineffective or not well tolerated. The efficacy

of amiodarone compared with that of an implantable cardioverter-defibrillator in patients with VT/VF and in survivors

ofcardiac arrest remains uncertain when total mortality is used as the primary endpoint of

comparison. Amiodarone suppresses ventricular ectopy and markedly suppresses nonsustained VT. It prevents

inducible VT/VF in a small number of patients, but slows VT rate in a larger number. The role of the drug in

prolonging survival in the postmyocardial infarction patient is unclear, although preliminary data from blinded studies

suggest that the drug decreases arrhythmia-related mortality. Similarly, in heart failure, amiodaronehas the potential

to reduce total mortality but appears to be selectively effective in nonischemic rather than in ischemic

cardiomyopathy. Intravenousamiodarone was recently introduced in the United States for the control of recurrent

destabilizing VT or VF resistant to conventional therapy. There is also evolving data indicating that the drug might be

the most potent agent in maintaining sinus rhythm in patients with atrial fibrillation or flutter converted chemically or

electrically to sinus rhythm. However, blinded controlled comparative studies involving sotalol, quinidine, or pure

class III drugs have not been carried out. The available data nevertheless suggest that, barring its side-effect

profile, amiodarone is a desirable prototype of a broad-spectrum antifibrillatory and antiarrhythmic compound. (Am J

Cardiol 1996;78(suppl 4A):4153)

Article Outline

1. PHARMACOLOGIC CONSIDERATIONS

2. HEMODYNAMIC EFFECTS OF AMIODARONE

3. AMIODARONE PHARMACOKINETICS

4. ANTIARRHYTHMIC AND ANTIFIBRILLATORY EFFECTS OF AMIODARONE: ESTABLISHED AND POTENTIAL

EXPANDING INDICATIONS

5. CURRENT STATUS OF THE ROLE OF INTRAVENOUS AMIODARONE IN THE ACUTE CONTROL OF VT/VF

6. AMIODARONE IN PATIENTS AT HIGH RISK FOR SUDDEN DEATH

7. SIDE-EFFECT PROFILE OF AMIODARONE

8. CONCLUSIONS

ReferencesPigmentation

Discoloration of the oral mucosa after drug use may be due to direct melanocytic stimulation, thedeposition of pigmented drug metabolites, or both. This reaction has long been recognized withantimalarial agents, particularly chloroquine, hydroxychloroquine, quinacrine, and quinidine (see Oraldrug-reaction patterns and associated drugs and drug classes in Introduction). Typically, suchpigmentation is most notable on the midposterior regions of the hard palate, appears bluish-black tobrown, and may be bilateral. A similar pattern is described with tranquilizers, especially chlorpromazine.

Macular or diffuse oral pigmentation may occur after the treatment of HIV disease with zidovudine,clofazimine, and ketoconazole. Minocycline use may be associated with bluish-gray to brownish mucosalpigmentation. Staining of underlying bony structures and tooth roots and enamel can occur. Staining ofthe bone and tooth roots is believed to play a major role in the most notable sites of discoloration, such asthe alveolar, gingival, and palatal tissues. Yet, staining of the mucosa alone has been reported in sitessuch as the tongue.

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