Answers to Self-Assessment examination of theAmerican Academy of Dermatology Identification No. 890-207

July 1990 issueof the JOURNAL OF THE AMERICAN ACADEMYOF DERMATOLOGY

DISCUSSION OF QUESTIONS 1-10

Onychomycosis is an infection of the nail by fungithat are classified by the type of microorganismpresent or by its route of invasion. Three clinicaltypes have been described by invasion site: distal orlateral subungual onychomycosis, superficial whiteonychomycosis, and proximal subungual onycho­mycosis. All three types may result in total dystro­phic onychomycosis. Although distal or lateral sub­ungual onychomycosis is the most common type,distal sparing in this case eliminates this diagnosis.

Superficial white onychomycosis is characterizedby small white superficial patches with distinct edgesand can occur on any part of the nail plate. Thesepatches, which can produce a rough surface on thenail plate, represent colonies of fungus that invadeonly the most superficial layers of the nail plate. Su­perficial white onychomycosis has not been reportedto affect the fingernails (although fingernail infec­tion has been induced experimentally) and prefer­entially involves the great toenail. The causative or­ganism is Trichophyton mentagrophytes in 90% ofcases. Candida albicans can cause this type of ony­chomycosis in infants and very young children. Me­chanical curettage or scraping of the nail followedbyapplication of topical antifungal agents is frequentlysuccessful in clearing superficial white onychomy­cosis. Glutaraldehyde 2%,which can produce a tan­brown discoloration, has alsobeen reported to be ef­fective.

Proximal subungual onychomycosis is the mostrare form of onychomycosis. It can affect either fin­gernails or toenails. The initial site offungal invasionis the epidermis of the proximal nail fold. Next, thefungus invades the undersurface of the nail plate inthe vicinity of the lunule where fungal growth islimited to the ventral surface of the nail plate. Clin­ically, one sees white patches near the proximal nail

fold, often withintervening areas ofnormalnail.Thesurface of the nail remains smooth.

The most common organism causing proximalsubungual onychomycosis is T. rubrum. Materialfor culture and/or KOH preparation shouldbe ob­tained from the deeper portion of the nail plate be­cause the dorsal surface will be fungus-negative.Treatment consists of systemic antifungals, such asgriseofulvin or ketoconazole, except whencausedbynondermatophytic fungi, in which case avulsion ofthe nail is necessary for cure. Patients treated withketoconazole for onychomycosis should be warnedto discontinue the drug if symptoms of hepatitis de­velop, and periodicliver function tests shouldbe ob­tained.

For this seriesthe recommended choices are: 1,b;2, e; 3, a; 4, d; 5, c; 6, a; 7, d; 8, b; 9, b; 10, a.

Dayna G. Diven, MD, and Sharon Raimer, MD,Galveston, Texas

REFERENCESAndre J, Achten G. Onychomycosis. Int J Dermatol 1987;

26:481-90.Hay RJ, BaranR. Fungal(onychomycosis) andotherinfections

of the nailapparatus. In: Baran R, Dawber RPR, eds.Dis­eases of the nailsand their management. Oxford: Blackwell,1984:121-44.

Noppakun N, Head ES. Proximalwhite subungualonychomy­cosisina patientwithacquiredimmune deficiency syndrome.Int J DermatoI1986;25:586-7.

Zaias N. Onychomycosis. In: The nail. Dermatol elin 1985;3:445-60.

Zaias N. Onychomycosis. In: The nail in health and disease.New York: Spectrum, 1980:91-113.

DISCUSSION OF QUESTIONS 11·19

The first description of sporotrichosis was madeby Schenck in 1898, in the same year he isolatedthecausative agent Sporothrix schenckii. Sporotricha-

163

164 Self-Assessment examination answers

sis is a cutaneous mycosis caused by the saprophiticdimorphic fungus, S. schenckii. The disease iscaused by inoculation of the organism into the skin,which may then spread through the lymphatics orthe blood stream to involve other organ systems.Primary cutaneous sporotrichosis is the most com­mon form. Systemic sporotrichosis is rare but maymanifest itself in muscle, bone, lung, eye, and thegenitourinary tract. .Because skin biopsy results areoften nonspecific, laboratory culture of the organismis usually essential to make the diagnosis. Earlyproper treatment is usually curative but routine an­timicrobial agents are of no benefit.

The primary cutaneous lesion appears as a red­purple necrotic nodule-the sporotrichotic chancre.In most cases, if untreated, the infection begins tospread along the lymphatics. Typically, a chain ofindurated red discrete nodulesextends up the arm orleg to the axillae or groin. In addition, the proximallymphatics becomeinflamed and thickened. Usuallyno pain, fever, or other symptoms occur.

The fungus is infrequently seen on microscopicexamination of biopsied material as organisms thatare seen with periodic acid-Schiff stain with cigar­shaped bodies of up to 8 pm in length. If the primarylesion is subjected to biopsy within the first fewweeks, it usually shows a nonspecific inflammatoryinfiltrate composed of neutrophils, lymphoid cells,plasma cells, and histiocytes. Older primary lesionsshow intraepidermal abscesseswithin a hyperplasticepidermis and the dermis may have small abscesses,giant cells, and granulomas. In the later stages, thenodules may show the characteristic arrangement ofthree zones: a central "suppurative" zone with neu­trophils, encircled by a "tuberculoid" zone, and, atthe periphery, a "round cell zone" of lymphoid andplasma cells.

The organism may be easily cultured in Sab­ouraud dextrose agar at room temperature. Micro­scopically, typical clusters of pear-shaped spores arefound at the tips of tiny conidiophores arising fromtangled masses of branched mycelia.

The common denominator of sporotrichosisthroughout the world is occupational exposure dur­ing agricultural work, gardening, or mining. Thesaprophyte has no predilection for age, race, sex, ornationality. The infection is found not only inhumans but also may occur in wild or domestic an­imals, including rats, mice, rabbits, dogs, cats,horses, donkeys, and cattle.

The common lymphatic form of sporotrichosis is

Journal of theAmerican Academy of

Dermatology

almost invariably and dramatically cured by super­saturated potassium iodide (SSKI). The recom­mended regimen is SSKl given orally with a start­ing dose of 10 drops, three times daily after meals,and gradually increased to the point of maximal tol­erance. Systemic sporotrichosisis resistant to iodidesbut often responds to intravenous therapy with am­photericin B.

For this series the recommended choicesare: 11,c; 12, b; 13, c; 14, b; 15, e; 16, d; 17, e; 18, e; 19, c.

Robert J. Cohen, MD, andFrancisco A. Kerdel, MD Miami, Florida

REFERENCESDunstan RW, Langham RF, Reimann RA, et al, Feline sporo­

trichosis: a report of five cases with transmission to humans.JAM ACAD DERMATOL 1986;15:37-45.

Homayoun A. Sporotrichosis; a historical approach. Int J Der­matol 1986;25:203-5.

Itoh M, Okamoto S, Kariya H. Survey of 200 cases of sporo­trichosis. Dermato1ogica 1986;172:209-13.

Lynch P, Voorhees J, Harrell ER. Systemic sporotrichosis.AnnIntern Med 1970;73:23-30.

DISCUSSION OF QUESTIONS 20~29

Glomus tumors are uncommon benign neoplasmsthat are believed to arise from the arterial segmentof the cutaneous arteriovenous shunt, the so-calledSucquet-Hoyer canal. This condition was first de­scribed by Masson in 1924. Glomus tumors can besingle or multiple; multiple tumors account for ap­proximately 10% of all glomus tumors. Multipleglomus tumors are more common in males with thenumber of lesions ranging from 10 to 90. More casesof multiple glomus tumors begin in childhood thansolitary glomus tumors.

Clinically, multiple glomus tumors appear ascompressible blue nodules ranging in size from 2 to3 mm to 3 em. They may involve any area ofthe skinwhereas solitary glomus tumors usually occur on anextremity and are frequently subungual. Multipleglomangioma may occur in a localized area (such asin this patient) or may be distributed diffusely overany area of the body. Glomus tumors have been re­ported rarely involving internal organs, such as thewall of the stomach; a rare but documented compli­cation of multiple glomus tumors is platelet seques­tration with resulting thrombocytopenia. Multipleglomus tumors are less painful and tender than thesolitary ones. Cavernous hemangiomas and pyo­genic granulomas recurring after treatment canhave a similar clinical appearance.

Volume 23Number IJuly 1990

Multipleglomustumorscan occursporadicallyormay be inherited in an autosomaldominantpatternwitha highdegreeof penetrance. Conant and Wie­senfeld described two brothers with multiple glo­mangiomas from a familywith sevenother affectedpersons. Sincethen,numerousother caseshavebeendescribed.

Multiple glomus tumors are characterized byvascular spaces that are irregularlyshapedand linedbyasingle layerofendothelialcells. Peripheral to theendothelial cells lie one to three layers of glomuscells. Glomus cells have a large, pale, round to ovalnucleus andeosinophilic cytoplasm. Solitaryglomustumors tend to have many more glomus cells sur­rounding the endothelialcells than do multiple glo­mus tumors. Whereas in solitary glomus tumorsmost vascular spaces are surrounded by many glo­muscells, manyvessels inglomangiomashavelargervascular luminaand have no or sparse glomus cells.Multiple glomus tumors showno fibrous capsule,incontrast to solitary glomus tumors. With electronmicroscopy, glomuscellsresemble vascularsmoothcells but are polygonal rather than elongate. Theycontain myofilaments arranged in bundles.

Numerous methods have been used to treat glo­mus tumors, both solitary and multiple. Surgicalexcision, electrocoagulation, and carbon dioxidela­ser havebeeneffective in ablating lesions. However,significant scarringresults.Goldmanreported treat­ment of an 8-year-old boy with pulsed ruby laser.Treatment was effective but minimal scarring didoccur. Argon and tunable dye lasers seemto be log­ical treatment options in the future.

For this series the recommendedchoices are: 20,b; 21, e; 22, d; 23, c; 24, e; 25, a; 26, c; 27, c; 28, e;29, c.

Bill Frank, MD, and Jeffrey Dover, MD,Boston, Massachusetts

REFERENCESConant MA, Wiesenfeld SL. Multiple glomus tumors of the

skin. ArchDermatoI1971;104:188-91.Goldman L.Lasertreatmentof multipleprogressive glomangi­

omas. ArchDermatol 1978;114:1853-4.Goldman L. Lasertreatmentof multiple progressive glomangi­

omas. Progress report 13 years after treatment. Arch Der­matol1981;1l7:1451-2.

HeithoffSJ, Horrell E, Burke E, et al. Glomus tumors of theupper extremity. experience with 12cases. J Am OsteopathAssoc 1985;85:453-7.

Jelinek JE. Aspects of heredity, syndromic association, andcourse ofconditions in which cutaneous lesionsoccursolitaryor in multiplicity. J AMACAD DERMATOL 1982;7:526-40.

Self-Assessment examination answers 165

DISCUSSION OF QUESTIONS 30-36

Erythermalgia (erythromelalgia) is a rare butdistinctive syndrome triggered by heat exposure.Painful, burning erythematous areas of the distalextremities develop after warming of the skin inthese areas from 32° to 36° C. The exact tempera­ture trigger point tends to be relatively constantforeach patient. Erythermalgia involves the lower ex­tremities more frequently than the upper, oftensymmetrically, and typically affects fingers or toes,palms or soles, or rarely more proximalareas of thedistal extremities. A burning sensation, associatedwith erythema and bounding distal pulses, developsrapidly after heat exposure. Although the vasodila­tion may contributetoincreased warmth in the area,the increasedblood flow is not required to maintainan episode. A blood pressure cuff that occludesproximal bloodflow, for example, will not abort anepisode. Symptoms are worsened by lowering andimproved by elevating affected areas, and patientsfrequently describe partial to complete relief ofsymptoms after cooling of involved areas. Episodestend to last minutesto a few hours; with time, indi­vidual episodes not only tend to occur more fre­quently but also may persist for days. Erosions orulcerations are uncommon, particularly in idio­pathic cases.

Erythermalgia may be primary (idiopathic) orsecondary; primary erythermalgia can be familial.In a review of 51 cases, ageofonsetfor patientswiththe primary form ranged from the first through theeighth decades (median 50 to 59 years); the rangefor the secondary forms of this syndromewas fromthe fifth through the eighth decades (median 60 to69 years). Thirty patients had primary erythermal­gia (male/female ratio 2:1); of the 21 patients withsecondary erythennalgia (male/female ratio 1:1),10 had an underlying myeloproliferative disorder,usuallypolycythemia vera. The other diseases asso­ciated with the secondary syndrome included hy­pertension, venous insufficiency, diabetes mellitus,systemic lupus erythematosus, and rheumatoid ar­thritis. Erythermalgia may precede the apparentonset of an underlying illness by several years.

Certain drugs have also been reported to causesyndromesthat mightbeconfusedwith erythermal­gia. Eisleret al. reported that nine patients receivinglong-term bromocriptine therapy for Parkinson'sdisease had an eruption resembling erythennalgia,with warm, erythematous, and edematous extremi­ties.However, thesepatients had lesspain and erup-

166 Self-Assessment examination answers

tions were not episodic or related to skin tempera­ture. A similar syndrome has been described inpatients treated with nifedipine. A syndrome ofpainful, sharply demarcated, intense erythema ofthepalms and fingers, followed by focal areasof'va­sospasm, bullae formation, and desquamation hasbeen described in patients with myelogenous leuke­mia being treated with doxorubicin, cytarabine,transfusions, and broad-spectrum antibiotic cover­age. A painful acral erythema has occurred afterbleomycin therapy,but thissyndrome isusually de­scribed assimilarto Raynaud's phenomenon withapostvasospastic erythema. Long-term infusion offluorouracil has been associated with the develop­mentin twopatients ofa tender, erythematous, des­quamative rash involving the palms, fingers, andsoles; thiswas not temperature dependent.

The differential diagnosis of erythermalgia in­volves arterial insufficiency (arteriosclerosis, throm­boangiitis obliterans), therecovery phase offrostbiteinjury, thehyperperfusion phase of Raynaud's phe­nomenon, early posttraumatic dystrophy (reflexsympathetic dystrophy), andneuropathy-associatedacral paresthesia with vasodilation, infantile acro­dynia(mercuryintoxication), and "nutritional mel­algia." These conditions may produce tender orpainful, somewhat erythematous distal extremitiesbut are not triggered by heat or relieved by cold(with theexception ofnutritional melalgia), occurina characteristic clinical setting, and typically resultin cool rather than warm areas of erythema.

The pathogenesis of this syndrome is poorlyunderstood and is probably multifactorial. Eryther­malgia was the presenting symptom in 26of 40 pa­tients with thrombocythemia (primary orassociatedwith polycythemia vera). Relief of symptoms inthese patients was achieved with the use of cycle­oxygenaseinhibitors (aspirin, indomethacin) orwithchemotherapy to reduce the elevated platelet count,thereby implicating platelets in the pathogenesis ofthis syndrome. Aspirin has been useful in relievingsymptoms, evenin patients without thrombocytosis

Journal of theAmerican Academy of

Dermatology

or obvious abnormal platelet dysfunction; indeed,dramatic reliefof symptoms by aspirinisoftenhelp­ful in the diagnosis of erythermalgia. Elevation andcooling of affected areas are also important thera­peutic measures. Three pediatric patients witherythennalgia weresuccessfully treated with nitro­prusside; two of these patients were hypertensiveduringtheir initialepisode. A varietyof other ther­apies of occasional benefit have been reported,including methysergide, epinephrine, and propra­nolol. Although both primary and secondary formsof erythermalgia may result in chronic symptoms,life-threatening developments are usuallylimitedtosecondary forms withprogression of the underlyingdisease.

For this series, the correctchoices are: 30, b; 31,a, b; 32, d; 33, e; 34, e; 35, c; 36, a, e.

Warren W. Piette, MD,Des Moines, Iowa

REFERENCES

BabbRR, Alarcon-Segovia D, Fairbairn JF II.Erythermalgia:review of 51 cases. Circulation 1964;24:136-41.

Brodmerkel GJ Jr. Nifedipine anderythromelalgia. Ann InternMoo 1983;99:415.

Burgdorf WHC, Gilmore WA, Ganick RG. Peculiar acralerythema secondary to high-dose chemotherapy for acutemyelogenous leukemia [Letter] . Ann Intern Moo 1982;97:61-2.

Eisler T, Hall RP, Kalavar KAR, et al. Erythromelalgia-likeeruption inparkinsonian patients treatedwithbromocriptine.Neurology 1981;31:1368-70.

Feldman LD, Ajani JA. Fluorouracil-associated dermatitisofthe handsand feet. JAMA 1985;254:3479.

Fisher JR, Padnick MB,Olstein S. Nifedipineanderythromel­algia [Letter].Ann Intern Med 1983;98:672-3.

Glusman M. The syndrome of "burning feet" (nutritionalmelalgia) as a manifestation of nutritionaldeficiency. Am JMoo 1947;3:211-23.

Levine LE, Medenica MM, Lorincz Al, et al. Distinctiveacralerythema occurring durign therapy for severe myelogenousleukemia. Arch DermatoI1985;121 :102-4.

Michiels JJ, Abels J, SteketeeJ, et al. Erythromelalgia causedbyplatelet-mediated arteriolar inflammation and thrombosisin thrombocythemia. Ann Intern Med 1985;102:466-471.

Ozsoylu S, Coskuna T. Sodium nitroprusside treatment inerythromelalgia. Eur J Pediatr 1984;141 :185-7.