Case presentation
A 45-year-old man born of a non-consanguineous marriage was referred for treatment of “atypical warts” on his hands, elbows, and axillae since childhood. These lesions were asymptomatic with no associated pruritus, pain, or bleeding. The patient had no previous treatment and no other medical comorbidities, and he denied a family history of similar skin lesions.
On clinical examination, the patient had a hoarse voice, skin-colored verrucous papules on the dorsal aspects of his hands, and hyperkeratotic verrucous plaques on elbow extensor surfaces as well as both axillae and his gluteal cleft (Figure 1). There were very subtle papular beads on the eyelid margins, and the oral mucosa was unaffected. Physical examination of other systems was unremarkable, and human immunodeficiency virus (HIV) and syphilis serology were negative.
Figure 1
(a) Verrucous papules on the dorsal aspect of hands bilaterally. (b) Symmetrical verrucous papules and plaques on bilateral elbows and axillae. (c) Subtle papular beading of eyelids
A biopsy specimen obtained from a verrucous plaque on the elbow is shown in Figure 2.
Figure 2
(a) Photomicrograph depicting acanthosis and hyperkeratosis of the epidermis. Vertically orientated deposits of faint eosinophilic, hyaline material fill the papillary and superficial dermis (hematoxylin and eosin, ×40). (b) Hyaline material arranged concentrically around blood vessels and eccrine glands (periodic acid-Schiff, ×100). PAS stain. (c) Close up micrograph of papillary dermis (hematoxylin and eosin, ×100)
A. Cutaneous amyloidosis
B. Lipoid proteinosis
C. Acral persistent papular mucinosis
D. Multicentric reticulohistiocytosis
E. Verruca vulgaris
Diagnosis
B. Lipoid proteinosis
Microscopic findings
The epidermis displays acanthosis and hyperkeratosis. Vertically orientated deposits of faint eosinophilic, hyaline material fill the papillary and superficial dermis. The same material involves the deeper dermis, associated with small blood vessels and the perineurium of nerves and arranged concentrically around eccrine glands. This material is strongly periodic acid–schiff (PAS) positive and diastase resistant, while staining with Congo Red is negative. Immunohistochemistry confirms the presence of Type IV collagen in the material.
Discussion
Lipoid proteinosis (also called “lipoidosis cutis et mucosae” or Urbach-Wiethe disease) is an autosomal recessive genodermatosis.1 Mutations in the extracellular matrix 1 (ECM1) gene on chromosome 1q21 cause this condition. Resultant dysfunction of the ECM1 protein is associated with multisystem disease involving the skin, eye, oropharynx, larynx, and brain.1
A case series of 24 patients from the Namaqualand area in South Africa highlights the clinical variability of lipoid proteinosis.2 The patient described above had a lifelong history of hoarse voice, a consistent feature of the disease. Other typical findings in the above patient include verrucous papules and plaques (Figure 1), subtle beading of the eyelid margins.2 Pustules, vesicles, and bullae are typical childhood features of lipoid proteinosis and are not usually present in adults. Other lipoid proteinosis features absent in this case include cutaneous scarring, alopecia, recurrent salivary gland swelling, a thickened frenulum with decreased tongue movement, stridor, and epilepsy.2 Neuropsychiatric and ophthalmologic manifestations were lacking in this patient but have been described elsewhere.3, 4
Although this patient was initially referred with warts, the symmetry and long duration of the lesions suggested a different diagnosis. Acral persistent papular mucinosis (APPM) is a subtype of localized lichen myxedematous that presents with asymptomatic skin-colored papules confined to the dorsal hands, wrists, and forearms.5 Unlike the above case, other areas such as the axillae and eyelid margins are not involved. Histologically APPM is characterized by well-circumscribed foci of mucin in the papillary and mid-dermis.4
Multicentric reticulohistiocytosis is a rare histiocytosis that mainly affects the skin and joints. Patients can present with skin colored to red-brown papules and nodules on the face, hands, neck, and trunk. Patients may also have nonspecific systemic symptoms, such as fever, malaise, and weight loss, as well as a destructive arthritis. Histologically, multicentric reticulohistiocytosis is characterized by aggregates of foreign body type giant cells, with eosinophilic ground-glass or foamy-vacuolated cytoplasm.5
As clinical manifestations of lipoid proteinosis are present from childhood, it is surprising that this patient presented for the first time at the age of 45 years. Although there is no specific treatment for lipoid proteinosis, the use of oral steroids, intralesional heparin, CO2 laser, and dermabrasion of the skin has been reported.6 This patient indicated satisfaction and relief at finally receiving a diagnosis and declined treatment. He also declined referral to a genetic counselor, as he does not intend to have children. This case of lipoid proteinosis in a skin of color will add to the image repository and aid dermatologists in improving competency.
Acknowledgment
Written consent obtained from the patient as well as ethical approval from Stellenbosch Health Research Ethics Committee (HEA-2022-26871 reference).
References
- , , , , . The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1. Exp Dermatol. 2007; 16(11): 881–90. https://doi.org/10.1111/j.1600-0625.2007.00608.x
- , , , , , , et al. Clinical and molecular characterization of lipoid proteinosis in Namaqualand, South Africa. Br J Dermatol. 2004; 151(2): 413–23. https://doi.org/10.1111/j.1365-2133.2004.06076.x
- , , , , , , et al. Translational neuroscience of basolateral amygdala lesions: studies of Urbach-Wiethe disease. J Neurosci Res. 2016; 94(6): 504–12. https://doi.org/10.1002/jnr.23731
- , , . Acral persistent papular mucinosis. J Am Acad Dermatol. 2004; 51(6): 982–8. https://doi.org/10.1016/j.jaad.2004.07.002
- , , , . Multicentric reticulohistiocytosis. Clin Dermatol. 2006; 24(6): 486–92. https://doi.org/10.1016/j.clindermatol.2006.07.010
- , , , . Lipoid proteinosis. J Oral Maxillofac Pathol. 2009; 13(2): 81–4. https://doi.org/10.4103/0973-029X.57675
First published at https://onlinelibrary.wiley.com/doi/10.1111/ijd.16679