Cutaneous Macroglobulinosis Presenting as Serpiginous Purpura, a Case Report and Literature Review

Figures & data

Figure 1 Clinical presentation: (A) multiple linear and serpiginous purpura on the abdomen, (B) back, (C) left thigh.

Figure 2 Histopathological and direct immunofluorescence findings: (A) Superficial perivascular infiltration with lymphocytes, neutrophils, nuclear dusts, and extravasated red blood cells, with superficial vascular lumen occlusions. (B) Positive Periodic acid–Schiff (PAS) staining in vessel lumens and vessel walls. (C) Positive IgM staining in vessel lumens and vessel walls. (D) Granular deposition of C3 in superficial vascular walls.

Figure 3 Resolution of lesions on the abdomen.

Table 1 Review of Case Reports and Case Series of Cutaneous Macroglobulinosis (CM)

Study	Age (yrs)/Sex	Onset of CM in Relation to WM Diagnosis (Years)	IgM Level (mg/mL)	Association with Neuropathy	Clinical Presentation	Histopathology	Special Stains	Direct Immunofluorescence	Treatment and Outcome
Mascaro et al 1982^Citation12	48/M	4 years after	34	NR	Multiple smooth pink pearly papules, some with central crust, on buttocks thighs and legs	Amorphous eosinophilic deposit in dermis, transepidermal elimination	PAS+	Positive for IgM, but negative for IgA and IgG	NR
Harnalikar et al 2010^Citation13	48/M	4 years before	20.2	Numbness and tingling present	Multiple painful, hyperkeratotic deep-seated papules over the pressure areas of both soles	Homogenous nodular deposits in dermis and in newly formed blood vessels	PAS+ Congo red -	Positive for IgM, but negative for IgA and IgG	Cyclophosphamide, lesions mostly resolved
Lüftl et al 2010^Citation14	43/M	Few months before	6.98	NR	Multiple skin-colored to red-brown papules (unknown location)	Homogenous eosinophilic deposits in dermis	PAS+ Congo red - Thioflavine – IgM+	Positive for IgM	Rituximab, unknown outcome
Gressier et al 2010^Citation10	Case 1 71/M	Concurrent	18.5	Symmetrical peripheral neuropathy all 4 limbs	Hyperkeratotic skin-colored papules with some central crust on both knees	Nodular eosinophilic infiltration in dermis	PAS+ Amyloid-specific stain -	Positive for IgM	Rituximab and chlorambucil, lesions resolved
	Case 2 65/M	Concurrent	15	Lower limb paresthesia	Multiple crusted papules, necrotic and ulcerated nodules and plaques on buttocks, upper limbs and lower limbs	Nodular eosinophilic infiltration in dermis, transdermal elimination	PAS+ Amyloid-specific stain – IgM+	NR	Chlorambucil, rituximab and fludarabine, patient died after 5 sessions
Marchand et al 2011^Citation15	67/M	Concurrent with WM relapse	Elevated	NR	Multiple erythematous,1–2 mm papules on knees and calves	Eosinophilic infiltrate in superficial and mid-dermis	PAS+ Congo red -	Positive for IgM	Bortezomib and rituximab, skin lesions unchanged
Camp et al 2012^Citation9	Case 1 40/F	3–4 years before	46.2	NR	Skin-colored papules on extensor surfaces of extremities and forehead	Deposition of eosinophilic material in dermis	PAS+ Congo red -	Positive for IgM	Declined treatment
	Case 2 83/F	Concurrent	5	NR	Erythematous, non-blanching papules and plaques on face, upper and lower extremities	Occlusion of blood vessel by pink homogenous materials and extravascular deposition in dermis	PAS+ Congo red – IgM+	Positive for IgM	Declined treatment
	Case 3 80/M	Unknown time after WN diagnosis	301.6	NR	Painful erythematous papules and nodules with central ulceration on lower extremities	Occlusion of blood vessel by pink homogenous materials and extravascular deposition in dermis	NR	Positive for IgM Negative for IgA and IgG	Rituximab, unknown outcome
D’Acunto et al 2014^Citation16	70/M	13 years after	22.9	NR	Painful hyperkeratotic nodules on both soles	Hyperplastic and hyperkeratotic epidermis, amorphous materials in dermis and intravascular space	PAS+ Congo red- IgM +	NR	NR
Oshio-Yoshii et al 2016^Citation8	63/M	1 year later	NR	NR	Reddish papules on right medial malleolar	Eosinophilic amorphous material in dermis	PAS+ Congo red- IgM + (also seen in vessel wall, intra-/perivascular space)		Rituximab 4 sessions, lesions resolved but then relapsed
Roupie et al 2019^Citation17	56/M	Concurrent	NR	NR	Papules covered by thick hyperkeratotic layer on both soles	Amorphous deposits in dermis	PAS+ Congo red- IgM +	NR	Rituximab, cyclophosphamide and corticosteroid, lesions resolved
Fayne et al 2019^Citation18	56/F	1 month after	4096	NR	Disseminated crusted papules and nodules with eschars on face trunk and extremities	Amorphous deposits in dermis	PAS+ Congo red weakly+ IgM +	NR	Rituximab, ifosfamide, carboplatin, etoposide and ibrutinib, unknown outcome
Hassab-El-Naby et al 2020^Citation4	50/F	Few months after	22	Peripheral neuropathy of upper and lower limbs	Multiple erythematous to hyperpigmented papules and nodules with central crust on face, eyelids and upper limbs	Dermal infiltration of homogenous eosinophilic materials	PAS+ Congo red - IgM+	NR	R-CHOP, patient died after 2 sessions
Our study	78/M	Concurrent	>58.5	None	Multiple linear and serpiginous purpura on abdomen and both thighs	Vasculopathy and vasculitis	PAS+ Congo red - IgM+	-Homogenous deposition of multiple Ig and C3 in vascular lumen -Granular deposition of C3 at vessel wall	Rituximab and bendamustine, lesions resolved

Abbreviations: M, male; F, female; C, complement; IgM, immunoglobulin M; NR, not reported; PAS, periodic acid–Schiff stain; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone.

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