PEDIATRIC DERMATOLOGY PHOTOQUIZ Editor: Maureen Rogers, M.D., F.A.C.D. SKIN ULCERS AND BONE PAIN IN A HEALTHY 6-YEAR-OLD FEMALE Ingrid C Polcari, M.D.,* Rebecca Reindel, M.D.,† Ellen Chadwick, M.D.,† Agatha Bogard, M.D.,‡ Pauline Chou, M.D.,‡ and Sarah Chamlin, M.D.* *Department of Pediatric Dermatology, †Department of Infectious Diseases, ‡Department of Pathology, Children’s Memorial Hospital, Chicago, Illinois Case Presentation A previously healthy 6-year-old girl presented to the emergency department with a 1-month history of ankle pain, elbow pain, and skin lesions. The skin lesions had started as small erythematous papules on the arm and subsequently enlarged, and she had been treated for presumed bacterial skin infection with cephalexin and mupirocin. Despite this ther- apy, the lesions enlarged and became purulent. Concurrently she had ankle pain and was treated with casting for a probable fracture. Just before presentation to our facility, the cast was removed because of drainage revealing a skin ulcer. The patient was well appearing and afebrile throughout this course. Laboratory studies were remarkable for a white blood cell count of 23.3 9 103/lL with 65% neutrophils, an erythrocyte sedimentation rate of 113 mm/hour, and a C-reactive protein level of 10 mg/dL. Radiographs of her left elbow and right ankle showed lytic lesions with a moth-eaten destructive appearance of the left lateral supra- condylar process (Fig. 1A) and of the distal fibular metaphysis (Fig. 1B), suggestive of osteomyelitis. Skin examination revealed a 1-cm round ulceration with a clean base over the left elbow with minimal surrounding erythema and purulent drainage (Fig. 2). On the left forearm there was a 1-cm crusted papule and on the right lateral malleolus a 0.8-cm 9 1.5-cm superficial round ulceration with a clean base and bloody exudate. A skin biopsy was performed on the left forearm and a bone biopsy was taken from the right tibia. A chest radiograph revealed a large, left lower lobe consolidation (Fig. 3). What is the diagnosis? A RED, WHITE, AND BLUE PLAQUE ON THE FLANK OF A NEWBORN Erica G. Lau, D.O.,* Cynthia Reyes, M.D.,† Shelly Stepenaskie, M.D.,‡ and Barrett Zlotoff, M.D.* *Department of Dermatology, †Department of Pediatric Surgery, ‡Department of Dermatopathology, University of New Mexico, Albuquerque, New Mexico Case Presentation An otherwise healthy full-term Caucasian boy was noted to have a “bruise” on the left flank at birth. He was born via caesarian section after an uncompli- cated prenatal course. Platelets were high (435 9 109/L), but the remainder of the complete blood count and routine biochemistry tests were within normal limits. Physical examination of the left flank demon- strated a well-demarcated, targetoid-appearing, 9-cm 9 11-cm oval, soft plaque (Fig. 1). There were three obvious zones of discoloration. The center of the plaque was blue-gray with overlying telangiec- tasias and a white rim of pallor. The periphery of the plaque was red-purple without telangiectasias. The skin involved was soft and without hypertrichosis or ulceration. No warmth or palpable thrill were felt. Full skin examination revealed no other abnormal- ities. Incisional biopsy performed by pediatric sur- gery, including portions from the red, white, and blue areas, was obtained for histopathologic exam- ination (Figs. 2 and 3). What is the diagnosis? PALMOPLANTAR KERATODERMA IN A 7-YEAR-OLD BOY Marı́a Castellanos González, M.D.,* Belén Rubio González, M.D.,* Inma Garcı́a Cano, M.D.,* Jimena Sanz Bueno, M.D.,* Gisela Petiti Hebe, M.D.,* and Concha Postigo, M.D.* *Department of Dermatology and Venereology, 12 de Octubre Hospital, Madrid, Spain Case Report A 9-year-old boy presented with persistent thicken- ing and scaling on his palms and soles, present since the age of 1 year. He had friable gums and a history of premature shedding of his deciduous teeth and, later, most of his permanent teeth. There was no family history of psoriasis, ichthyosis, or palmopl- antar keratodermas. Physical Examination There was a symmetric, well-dermacated, yellowish keratoderma on the palms and soles (Figs. 1 and 2), extending to the dorsal surfaces of the hands (Fig. 3) and feet. There were also erythematous, scaly, psoriasiform plaques on his elbows and knees and the dorsal aspects of the fingers (Fig. 3). His gums were erythematous and edematous, and there was an absence of the majority of teeth (Fig. 4). Complete blood count showed no abnormality. What is the diagnosis? Figure 2. Figure 3. Figure 1. Figure 2. Figure 3. Figure 1. Figure 2. Figure 3. Figure 4. A B Figure 1. 749 SKIN ULCERS AND BONE PAIN IN A HEALTHY 6-YEAR-OLD FEMALE Diagnosis: Disseminated blastomycosis Histopathology Histologic examination of the skin revealed an ulcerated, spongiotic epidermis with a serous crust and acute inflammatory cells. There was a dense plasmacytic infiltrate within the dermis with admixed multinucleated giant cells (Fig. 4). A peri- odic acid-Schiff–stained section revealed a multi- nucleated giant cell containing magenta-stained budding organisms (Fig. 5). Histologic examination of bone showed suppurative and granulomatous inflammation, also with characteristic yeasts. Tissue culture later grew Blastomyces derma- titidis. Discussion B. dermatitidis is a dimorphic fungus and the causative agent of blastomycosis. Blastomycosis is endemic to North America, particularly in the Midwest and Southeast. Although primary cutane- ous blastomycosis can occur in the setting of penetrating trauma, skin involvement is usually secondary. Disease is often acquired through inha- lation of conidia from infected soil, making the lungs the typical first site of infection. Organisms then travel through blood or lymphatics to involve the skin. Because pulmonary infection is asymptomatic in up to half of affected patients, cutaneous findings are often the first sign of infection. Cutaneous blastomycosis most commonly presents as well- demarcated papulopustules or verrucous, vegetative plaques. Ulceration may occur and appear similar to pyoderma gangrenosum (1,2). Approximately 25% of disseminated blastomycosis cases have associated osteomyelitis, so bone pain or swelling should be investigated with imaging (3). The vertebrae, ribs, skull, and long bones are most often affected, and bony involvement confers a higher risk of relapse. Genitourinary and central nervous system involve- ment are rare. Diagnosis is made by identification of the characteristic broad-based budding yeast forms in tissue or culture. Severe or progressive disease should be treated with intravenous amphotericin B followed by oral itraconazole. When there is bony involvement, treatment courses of up to 12 months are recommended (4). This patient was treated with a 14-day course of intravenous liposomal ampho- tericin B and continues on oral itraconazole 5 mg/kg per dose twice daily with a planned treatment course of 1 year. During hospitalization she required multiple wound debridement surgeries with vac- uum-assisted closure dressings postoperatively. Ulti- mately she required a split-thickness skin graft on the affected leg. References 1. Sobera JO, Elewski BE. Fungal diseases. In: Bolognia JL, Jorizzo JL, Rapini RP, eds. Bolognia textbook of dermatol- ogy, 2nd ed. Barcelona: Mosby Elsevier, 2008:1155–1156. 2. Mason AR, Cortes GY, Cook J et al. Cutaneous blastomy- cosis: a diagnostic challenge. Int J Dermatol 2008;47:824– 830. 3. Oppenheimer M, Embil JM, Black B et al. Blastomycosis of bones and joints. South Med J 2007;100:570–578. 4. Chapman SW, Dismukes WE, Proia LA et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis 2008;46:1801–1812. Address correspondence to Sarah Chamlin, M.D., Department of Pediatric Dermatology, 2300 Children’s Plaza, Box 107, Chicago, IL 60614-3363, USA, or e-mail:
[email protected]. A RED, WHITE, AND BLUE PLAQUE ON THE FLANK OF A NEWBORN Diagnosis: Congenital nevus Microscopic Findings Histopathologic examination revealed rows of small, round, basaloid cells with occasional mitoses (Fig. 3). Cells stained strongly positive for melan A (melanoma-associated antigen recognized by T cells) (Fig. 4), S-100, and vimentin. Cells were negative for CD31, CD34, actin, desmin, neuron-specific eno- lase, CD56, chromogranin, myogenin, synaptophy- sin, and pancytokeratin. Fluorescence in situ hybridization interpreta- tion was negative for the translocation of Ewing’s sarcoma. Histologic findings were consistent with a congenital melanocytic nevus (CMN). Discussion Congenital melanocytic nevi occur in 1% to 6% of newborns and are present at birth. Common classi- fication is based on size, measured according to the largest estimated diameter in adulthood: small (20 cm). General guidelines suggest that nevi measuring 9 cm in diameter on the head and 6 cm on the body of a neonate could be considered large (1,2). CMN usually present as well-demarcated, round to oval hyperpigmented papules or plaques that become darker in color and hypertrichotic with age, but at birth they can display multiple colors and irregular topography and have been known to mimic vascular lesions. This has occurred especially with large or giant CMN (3). Large or giant CMN have a definite risk of development of melanoma and of associated neuro- cutaneous melanosis (NCM). It is controversial whether small or medium CMN carry a high risk of either. With regard to NCM, recent reports suggest that the size of the lesion is less important than the number of satellite nevi (4). As for melanoma, the risk of small or medium CMN developing melanoma is 0% to 4.9% (5). Large CMN carry a lifetime risk of 4.5% to 15%, with 70% of cases of malignant melanoma occurring before 10 years of age (3). Therefore, during the particular at-risk period, at-home skin checks are recommended in addition to medical evaluation. Palpation is of great importance because melanoma in this population will arise below the dermoepider- mal junction (3). Prophylactic excision is controver- sial because it has not been shown to be effective in preventing malignant melanoma in large congenital nevi, but could be recommended in any CMN (small, medium, or large) if the lesion is disfiguring, the family is unwilling to perform monthly self- checks, or the patient cannot be followed up regularly for medical evaluation. This is a unique presentation of a large CMN mimicking a vascular tumor. At 6-week follow-up examination revealed a gray-blue and tan plaque with darker brown macules scattered throughout (Fig. 5), more consistent with a classic presentation of a CMN. Hypertrichosis, another common finding in CMN, was also noted at 3 months of age. The patient will be monitored every 3 to 6 months for the first 2 years of life and annually thereafter. References 1. Kadanoga JN, Frieden IJ. Neurocutaneous melanosis: def- inition and review of the literature. J Am Acad Dermatol 1991;24:747–755. 2. Marghoob AA, Schoenbach SP, Kopf AW et al. Large congenital melanocytic nevi and the risk for the development of malignant melanoma: a prospective study. Arch Dermatol 1996;132:170–175. 3. Marghoob AA. Congenital melanocytic nevi: evaluation and management. Dermatol Clin 2002;20:607–616. 4. Marghoob AA, Dusza S, Oliveria S et al. Number of satellite nevi as a correlate for neurocutaneous melanocytosis in patients with large congenital melanocytic nevi. Arch Der- matol 2004;140:171–175. 5. Rhodes AR, Melski JW. Small congenital nevocellular nevi and the risk of cutaneous melanoma. J Pediatr 1982;100: 219–224. Address correspondence to Erica G. Lau, D.O., 1021 Medical Arts Avenue NE, Albuquerque, NM 87102, or e-mail: elau@ salud.unm.edu. PALMOPLANTAR KERATODERMA IN A 7-YEAR-OLD BOY Diagnosis: Papillon-Lefèvre syndrome Further Investigations and Progress Genetic studies showed a homozygosus mutation in the cathepsin C gene, and TCD4 cell, B cell, and natural killer cell levels were low. Acitretin 10 mg/day was started in addition to emollients. The patient was referred to the Faculty of Periodontics of Complutense University of Madrid. He has been receiving treatment for more than 10 years. The psoriasiform plaques on his elbows and knees have disappeared, and the lesions on the palms and soles have improved considerably. In addition, new teeth erupted during acitretin treat- ment. During this period, all blood analyses have remained normal. Discussion Papillon-Lefèvre syndrome (PLS), first described in 1924, is an autosomal-recessive genodermatosis characterized by erythematous palmoplantar hyper- keratosis, repeated episodes of periodontitis, and premature loss of teeth. The frequency is approxi- mately 1 to 4 in 1 million people and onset is between the ages of 1 and 3 years (1). The kerato- derma commonly involves the entire surface of the palms and soles and often extends to the dorsa of the hands and feet. The plantar surface is the most severely involved and causes difficulty in walking. These patients may also have psoriasiform plaques on the elbows and knees (2). Periodontitis, with marked gingival inflamma- tion, often begins at the age of 3 or 4 years and leads to loss of structurally normal teeth in most patients (3). Other rare manifestations are follicular hyper- keratosis, acroosteolysis, arachnodactyly and men- tal retardation (1,4). A small group of patients have high suscepti- bility to infections, and abnormalities of neutrophil, lymphocyte, and monocyte functions have been demonstrated. Skin infections and pyogenic liver abscess have been reported (5). The pathogenesis of this disorder is unclear. Mutations in both alleles of the cathepsin C gene have been reported. These result in low activity of this peptidase, which processes several serine prote- ases important in immune and inflammatory responses of myeloid and lymphoid cells (6). All patients are homozygous for these cathepsin C mutations. Mutations in the same gene occur in two other entities—Haim-Munk syndrome and prepubertal periodontitis—in each of which severe early periodontitis is also seen. Papillon-Lefèvre syndrome requires a multi- disciplinary approach to treatment with involvement of a dermatologist, pediatrician, and pediatric den- tist. Skin manifestations can be treated with emol- lients, and oral retinoids (acitretin or isotretinoin) have proven to be effective. These drugs regulate cell proliferation and differentiation and may have a role in antibody production and effects on various functions of granulocytes and monocytes. Retinoids have been described to be of benefit for keratoderma and periodontitis. If started during the eruption of deciduous teeth and maintained while the perma- nent teeth are developing, retinoids can modulate the course of the periodontitis and enable retention of teeth of each dentition (7). The patient must be referred to a dentist for good dental care and use of prophylactic antibiotics to further control the peri- odontitis. We present the case of a rare disease with palmoplantar keratoderma and periodontitis, stress- ing the importance of early treatment as a way to control the periodontitis and avoid some loss of teeth. References 1. Hart TC, Shapira L. Papillon-Lefèvre syndrome. J Periodon- tol 2000 1994;6:88–100. 2. Siragusa M, Romano C, Batticane N et al. A new family with Papillon-Lefèvre syndrome: effectiveness of etretinate treat- ment. Cutis 2000;65:151–155. 3. Janjua SA, Khachemoune A. Papillon-Lefèvre syndrome: case report and review of the literature. Dermatol Online J 2004;10:13. 4. Haneke E. The Papillon-Lefèvre syndrome: keratosis palmo- plantaris with periodontopathy: report of a case and review of cases in the literature. Hum Genet 1979;51:1–35. 5. Almuneef M, Al Khenaizan S, Al Ajaji S et al. Pyogenic liver abscess and Papillon-Lefèvre syndrome: not a rare assoca- tion. Pediatrics 2003;111:e85–e88. 6. Allende LM, Garcı́a-Pérez MA, Moreno A et al. A genetic study of cathepsin C gene in two families with Papillon- Lefévre syndrome. Mol Genet Metab 2003;79:146–148. 7. Gelmetti C, Nazzaro V, Cerri D et al. Long-term preservation of permanent teeth in a patient with Papillon-Lefèvre syndrome treated with etretinate. Pediatr Dermatol 1989; 6:222–225. Address correspondence to Marı́a Castellanos González, M.D., Calle Costa Brava 18, 3G 28034 Madrid, Spain, or e-mail:
[email protected]. Figure 4. Figure 4. Figure 5. Figure 5. 750