| Abstract|| |
Lichen myxoedematosus (LM), a form of primary cutaneous mucinosis, may present either as localized less severe form called papular mucinosis or diffuse more severe form called scleromyxoedema. The diffuse form is almost always associated with monoclonal gammopathy, whereas localized form is not. We report an atypical case of localized form of LM associated with multiple myeloma in a 66-year-old male, who presented with asymptomatic waxy papular eruption on extremities, which on histopathological examination confirmed the diagnosis of cutaneous mucinosis. After initially being put on steroids and hydroxychloroquine with minimal improvement, patient subsequently presented with encephalopathy and on evaluation revealed hypernatremia, hypercalcemia, hypergammaglobulinemia, reversal of albumin-globulin (A/G) ratio, azotemia, and lytic lesions in skull X-ray. Bone marrow aspiration and biopsy confirmed multiple myeloma. Patient was successfully treated with standard treatment regimen for multiple myeloma with bortezumib and dexamethasone and his skin lesions subsided completely.
Keywords: Cutaneous mucinosis, lichen myxoedematosus, multiple myeloma, papular mucinosis, scleromyxoedematosus
|How to cite this article:|
Rather PA, Hussain M, Bagdadi F. Localized cutaneous mucinosis associated with multiple myeloma: A rare presentation. Indian J Dermatol 2014;59:422
|How to cite this URL:|
Rather PA, Hussain M, Bagdadi F. Localized cutaneous mucinosis associated with multiple myeloma: A rare presentation. Indian J Dermatol [serial online] 2014 [cited 2020 Nov 30];59:422. Available from: https://www.e-ijd.org/text.asp?2014/59/4/422/135538
What was known?
Localized form of cutaneous mucinosis is not usually associated with paraproteinemia, plasma cell dyscrasia, multiple myeloma though generalized form can be. There is a paucity of data with respect to this association.
| Introduction|| |
Cutaneous mucinosis are the name given to heterogeneous group of disorders, affecting the skin and/or other organ systems, characterized by deposition of mucin (glycosaminoglycans) in skin. Lichen myxoedematosus (LM), first described in 1906,  presents as localized papular, diffuse scleromyxoedema and as atypical forms. 
The generalized form has associated monoclonal gammopathy, usually of lambda type.  Localized LM is confined to a few sites and is not associated with systemic findings and monoclonal gammopathy. We are reporting a rare atypical case of localized papular mucinosis associated with multiple myeloma, for which, to the best of our knowledge there is a paucity of data available in the literature.
| Case Report|| |
A 66-year-old man presented to the department of dermatology of a tertiary care center in August 2011, with the complaints of asymptomatic flesh-colored skin lesions on hands, forearms, feet, and legs since 3 months. General physical and systemic examinations were normal. On cutaneous examination, there were bilaterally symmetrically distributed non-exuding, non-scaly, firm, waxy, non-tender papules and plaques on distal extremities, with sparing of scalp, face, and trunk [Figure 1] and [Figure 2]. Mucus membrane, nail, and hair examinations were normal. Patient was put on topical steroids (clobetasol propionate, 0.05% ointment) and oral antihistamines (levocetirizine, 10 mg once daily) with the clinical impression of lichenoid eruption. Patient showed minimal response to the treatment and on a subsequent follow-up, skin biopsy and other investigations were advised. Patient reported back in October 2011 with skin biopsy and other investigation reports. Complete blood count, liver function tests, kidney function tests, and urine examination were normal. Antinuclear antibodies were negative. Skin biopsy of one of the lesions showed unremarkable epidermis with dermis showing pallor, loosening of collagen bundles, mild chronic perivascular inflammation, and mucin deposition [Figure 3]. Patient was labeled as a case of localized papular mucinosis and put on treatment with oral steroid (prednisolone, 30 mg once a day and hydroxychloroquine, 200 mg twice a day). On follow-up at 2 and 4 weeks, patient did not have much improvement in cutaneous lesions. On subsequent follow-up in December 2011, cutaneous lesions were in status quo and patient also had altered sensorium, recurrent vomiting, anorexia, and constipation. On general physical examination, patient was found to be dehydrated. Respiratory cardiovascular, and per abdomen examinations were normal. Nervous system examination revealed patient to be in altered sensorium. Physician consultation was advised and patient was found to be in grade II encephalopathy without any meningeal signs or focal neurological deficit. Complete blood count was normal. Liver function tests showed hyper gammaglobulinemia with reversal of A/G ratio (total proteins, 12.6 g/dL; albumin, 2.8; and globulin, 9.8). Kidney function tests revealed azotemia (blood urea, 108 and serum creatinine, 3.6). Serum electrolytes revealed hypernatremia (serum sodium, 164; serum potassium, 3.6, pH, 7.46; and bicarbonate, 24). Serum calcium levels were repeatedly high (15.6 mg/dL, 14.8 mg/dL). Chest X-ray was normal but skull X-ray showed punched out lytic lesions [Figure 4]. ECG, thyroid profile, and lipid profile were normal. Ultrasound abdomen and pelvis for hepatobiliary system and renal system were normal. Noncontrast computerized tomography (CT) head was normal. With a suspicion of multiple myeloma, bone marrow aspiration and bone marrow biopsy were done, which showed 69% plasmacytosis, thus confirming the diagnosis of multiple myeloma [Figure 5]a and b. Serum and urine electrophoresis were positive for M protein. Immunoglobulin G levels were raised, B2 microglobulin levels were elevated to 6.8 mg/L. Patient was started on standard treatment regimen for multiple myeloma in January 2012, with bortezumib and dexamethasone (regimen of days 1, 4, 8, and 11 and repeat at day 21) and also symptomatically treated for hypernatremia and hypercalcemia. So far, patient has received four cycles of the treatment regimen and is doing well. His cutaneous lesions have subsided almost completely.
|Figure 3: Histopathological appearance of skin biopsy showing pallor, loosening of collagen bundles, and mucin deposition in the dermis (H and E, ×40)|
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|Figure 5: (a and b) Histopathological appearance of bone marrow biopsy displaying plasmacytosis (H and E, ×40)|
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| Discussion|| |
Cutaneous mucinosis, characterized by deposition of mucin (glycosaminoglycans) in skin, may be primary or secondary to collagen vascular diseases, mesenchymal and neural tumors, eosinophilia myalgia syndrome, histiocytosis, etc., Primary cutaneous mucinosis is further divided into diffuse, focal, and follicular varieties. Diffuse cutaneous mucinosis includes generalized and pretibial myxoedema, reticular erythematous mucinosis, scleroedema, lichen myxoedema. LM, first described in 1906,  was earlier classified in 1953 by Montgomery and Underwood into four subtypes: Generalized lichenoid papular eruption, discrete papular form, localized-to-generalized lichenoid plaques, and urticarial plaques and nodular eruptions. ,
It was reclassified in 2001 into a) generalized form called scleromyxoedema, usually associated with monoclonal gammopathy; b) localized forms without demonstrable paraproteins such as discrete papular LM, acral persistent papular mucinosis, self-healing papular mucinosis, papular mucinosis of infancy, and nodular LM; and c) atypical forms such as scleromyxoedema without monoclonal gammopathy, localized LM with monoclonal gammopathy, localized LM with mixed features of different subtypes, and not otherwise specified variety. 
In 2006, a self-healing variant was included in the discrete papular LM category. 
Histopathological findings in all forms of LM are characterized by dermal mucin comprised of acid glycosaminoglycans. The mucin in scleromyxoedema is diffuse, accompanied by collagen deposition and increased number of large fibroblasts. In discrete papular form, the mucin may be focal or diffuse, with no increase in collagen and fewer fibroblasts.
Scleromyxoedema, the most common form, presents as widespread symmetric eruption of usually linearly arranged firm, dome-shaped, waxy papules, nodules, or plaques, involving the face as well as trunk and extremities. As the condition progresses, there may be skin stiffening, sclerodactyly, and decreased mobility of mouth and joints resembling scleroderma. It is almost always associated with paraproteinemia (83.2%), usually IgG with light chains.  It may be associated with other systemic disorders such as multiple myeloma, lymphoma, leukemia, and other organ involvement. Although a mild plasmacytosis may be found in the bone marrow, scleromyxoedema monoclonal gammopathy progresses to multiple myeloma in only 10% of cases.  Diagnosis of scleromyxoedema should fulfill the following criteria: (1) Generalized papular and sclerodermoid eruption; (2) mucin deposition, fibroblast proliferation, and fibrosis; (3) monoclonal gammopathy; and (4) the absence of thyroid disease.
In LM or papular myxoedema, usual age of presentation is 30-70 years with equal sex ratio. The primary lesion, like that in generalized form, is a 2-4 mm dome-shaped flesh-colored or erythematous papule, discrete and/or grouped, confined to few sites particularly dorsal hands, face or extensor surfaces of arms and legs, without systemic involvement. Papules often have a striking pattern of parallel ridges. The criteria for localized LM are as follows: (1) Papular or nodular/plaque eruption; (2) mucin deposition with variable fibroblast proliferation; and (3) the absence of both monoclonal gammopathy and thyroid disease.
Our 60-year-old male patient presented with localized form of LM as suspected from clinical features and confirmed by histopathological examination. The patient was subsequently found to have multiple myeloma from clinical features, hypercalcemia, positive bone marrow aspiration and biopsy findings, positive serum and urine protein electrophoresis for M protein, raised IgG levels, raised B2 microglobulin, raised gammaglobulins, and lytic lesions in skull. Thus, our patient had atypical variety of LM. To the best of our knowledge, there is a paucity of data available in the literature regarding the association of cutaneous mucinosis with plasma cell dyscrasia , and multiple myeloma. , Very few case reports of cutaneous mucinosis as such have been reported from India. ,, With this background in mind, we are reporting this rare association.
| References|| |
|1.||Dubreuilh W. Fibromes miliaries folliculaires: Sclerodermie consecutive. Arch Dermatol Syphilol 1906;7:569. |
|2.||Rongioletti F, Rebora A. Updated classification of papular mucinosis, lichen myxoedematosus, and scleromyxoedema. J Am Acad Dermatol 2001;44:273-81. |
|3.||Lai a Fat RF, Suurmond D, Rádl J, van Furth R. Scleromyxoedema (lichen myxoedematosus) associated with a paraprotein, IgG 1 of type kappa. Br J Dermatol 1973;88:107-16. |
|4.||Montgomery H, Underwood LJ. Lichen myxoedematosus; differentiation from cutaneous myxoedemas or mucoid states. J Invest Dermatol 1953;20:213-36. |
|5.||Perry HO, Montgomery H, Stickney JM. Further observations on lichen myxoedematosus. Ann Intern Med 1960;53:955-69. |
|6.||Rongioletti F. Lichen myxoedematosus (papular mucinosis): New concepts and perspectives for an old disease. Semin Cutan Med Surg 2006;25: 100-4. |
|7.||Feldman P. Lichen myxoedematosus with plasma cell dyscrasia. Arch Dermatol 1968;97:606-8. |
|8.||Dinneen AM, Dicken CH. Scleromyxoedema. J Am Acad Dermatol 1995;33:37-43. |
|9.||Krebs A, Müller A. Lichen myxoedematosus and multiple myeloma type IgG/kappa. Hautarzt. 1980;31:649-53. |
|10.||Cheng S, Leach IH, Perkins W. A novel case of follicular mucinosis after autologous stem-cell transplantation for multiple myeloma. Clin Exp Dermatol 2011;36:635-7. |
|11.||Singh M, Kaur S, Kumar B, et al. Scleromyxoedema. Indian J Dermatol Venereol Leprol 1985;51:111-3. |
|12.||Bajaj AK, Gupta SC, Tripathi A, et al. Scleromyxoedema. Indian J Dermatol Venereol Leprol 1986;52:340-2. |
|13.||John TS, Nair VL, Sugathan P. Scleromyxoedema. Indian J Dermatol Venereol Leprol 1990;56:389-90. |
What is new?
Localized form of cutaneous mucinosis can either be associated with plasma cell dyscrasia/multiple myeloma or multiple myeloma may manifest as cutaneous mucinosis. A dermatologist should keep this clinical correlation in mind for all cases of cutaneous mucinosis.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]